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INTERNAL MEDICINE (180 journals)                     

Showing 1 - 180 of 180 Journals sorted alphabetically
Abdomen     Open Access  
ACP Hospitalist     Full-text available via subscription   (Followers: 9)
ACP Internist     Full-text available via subscription   (Followers: 10)
ACP Journal Club     Full-text available via subscription   (Followers: 11)
Acta Clinica Belgica     Hybrid Journal   (Followers: 1)
Acute and Critical Care     Open Access   (Followers: 11)
Acute Medicine     Full-text available via subscription   (Followers: 9)
Advances in Hepatology     Open Access   (Followers: 4)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
African Journal of Primary Health Care & Family Medicine     Open Access   (Followers: 6)
African Journal of Thoracic and Critical Care Medicine     Open Access  
American Family Physician     Full-text available via subscription   (Followers: 38)
American Journal of Hypertension     Hybrid Journal   (Followers: 31)
Anales de Medicina Interna     Open Access   (Followers: 1)
Anatomy & Physiology : Current Research     Open Access   (Followers: 9)
Angiology     Hybrid Journal   (Followers: 5)
Annals of Colorectal Research     Open Access   (Followers: 1)
Annals of Internal Medicine     Full-text available via subscription   (Followers: 392)
AORN Journal     Hybrid Journal   (Followers: 27)
Apollo Medicine     Open Access  
Archives of Drug Information     Hybrid Journal   (Followers: 5)
Archivos de Medicina Interna     Open Access   (Followers: 1)
Asia Oceania Journal of Nuclear Medicine & Biology     Open Access   (Followers: 4)
Asian Pacific Journal of Tropical Disease     Full-text available via subscription   (Followers: 3)
Australasian Physical & Engineering Sciences in Medicine     Hybrid Journal   (Followers: 1)
BMI Journal : Bariátrica & Metabólica Iberoamericana     Open Access   (Followers: 1)
BMJ Open Diabetes Research & Care     Open Access   (Followers: 35)
BMJ Quality & Safety     Hybrid Journal   (Followers: 69)
Bone & Joint Journal     Hybrid Journal   (Followers: 138)
Brain Communications     Open Access   (Followers: 4)
Brain Science Advances     Open Access  
Canadian Journal of General Internal Medicine     Open Access   (Followers: 2)
Cardiovascular Medicine in General Practice     Full-text available via subscription   (Followers: 7)
Case Reports in Internal Medicine     Open Access   (Followers: 1)
Cell Death & Disease     Open Access   (Followers: 3)
Cellular and Molecular Gastroenterology and Hepatology     Open Access   (Followers: 3)
Cephalalgia     Hybrid Journal   (Followers: 8)
Cephalalgia Reports     Open Access   (Followers: 4)
Chronic Diseases and Injuries in Canada     Free   (Followers: 1)
Clinical Ethics     Hybrid Journal   (Followers: 13)
Clinical Liver Disease     Open Access   (Followers: 5)
Clinical Nutrition     Hybrid Journal   (Followers: 98)
Clinical Thyroidology     Full-text available via subscription   (Followers: 1)
CNE Pflegemanagement     Hybrid Journal  
Communication Law and Policy     Hybrid Journal   (Followers: 5)
Current Diabetes Reports     Hybrid Journal   (Followers: 30)
Current Hepatology Reports     Hybrid Journal  
Current Research: Integrative Medicine     Open Access  
CVIR Endovascular     Open Access   (Followers: 1)
Der Internist     Hybrid Journal   (Followers: 12)
Diabetes     Full-text available via subscription   (Followers: 603)
Diabetes Care     Full-text available via subscription   (Followers: 578)
Diabetes Internacional     Open Access  
Diabetes Spectrum     Full-text available via subscription   (Followers: 17)
Diagnosis     Hybrid Journal   (Followers: 1)
Egyptian Journal of Bronchology     Open Access  
Egyptian Journal of Internal Medicine     Open Access   (Followers: 1)
Egyptian Journal of Neurosurgery     Open Access  
Egyptian Liver Journal     Open Access   (Followers: 2)
Egyptian Spine Journal     Open Access  
EMC - Aparato Locomotor     Hybrid Journal  
Endovascular Neuroradiology / Ендоваскулярна нейрорентгенохірургія     Open Access   (Followers: 1)
eNeuro     Open Access   (Followers: 3)
Ergonomics     Hybrid Journal   (Followers: 24)
European Journal of Inflammation     Open Access   (Followers: 2)
European Journal of Internal Medicine     Full-text available via subscription   (Followers: 10)
European Journal of Translational Myology     Open Access  
European Radiology Experimental     Open Access   (Followers: 2)
Head and Neck Tumors     Open Access   (Followers: 1)
Health Sociology Review     Hybrid Journal   (Followers: 14)
HemaSphere     Open Access   (Followers: 2)
Hepatology Communications     Open Access  
Hepatoma Research     Open Access   (Followers: 3)
Human Physiology     Hybrid Journal   (Followers: 5)
ImmunoHorizons     Open Access  
Immunological Medicine     Open Access  
Infectious Diseases: Research and Treatment     Open Access   (Followers: 5)
Inflammation and Regeneration     Open Access   (Followers: 2)
Inflammatory Intestinal Diseases     Open Access  
Innere Medizin up2date     Hybrid Journal   (Followers: 1)
Internal and Emergency Medicine     Hybrid Journal   (Followers: 5)
Internal Medicine Journal     Hybrid Journal   (Followers: 9)
International Journal of Abdominal Wall and Hernia Surgery     Open Access   (Followers: 1)
International Journal of Anatomy and Research     Open Access   (Followers: 2)
International Journal of Angiology     Hybrid Journal  
International Journal of Artificial Organs     Hybrid Journal   (Followers: 3)
International Journal of Hyperthermia     Open Access  
International Journal of Internal Medicine     Open Access   (Followers: 3)
International Journal of Noncommunicable Diseases     Open Access  
International Journal of Psychiatry in Clinical Practice     Hybrid Journal   (Followers: 6)
Iranian Journal of Neurosurgery     Open Access   (Followers: 1)
Italian Journal of Anatomy and Embryology     Open Access   (Followers: 1)
JAC-Antimicrobial Resistance     Open Access   (Followers: 4)
JAMA Internal Medicine     Full-text available via subscription   (Followers: 364)
JCSM Clinical Reports     Open Access   (Followers: 3)
JHEP Reports     Open Access  
JIMD Reports     Open Access  
JMV - Journal de Médecine Vasculaire     Hybrid Journal   (Followers: 1)
Joint Commission Journal on Quality and Patient Safety     Hybrid Journal   (Followers: 41)
JOP. Journal of the Pancreas     Open Access   (Followers: 2)
Journal of Basic & Clinical Physiology & Pharmacology     Hybrid Journal   (Followers: 1)
Journal of Bone Oncology     Open Access   (Followers: 1)
Journal of Cancer & Allied Specialties     Open Access  
Journal of Clinical and Experimental Hepatology     Full-text available via subscription   (Followers: 3)
Journal of Clinical Movement Disorders     Open Access   (Followers: 3)
Journal of Community Hospital Internal Medicine Perspectives     Open Access  
Journal of Cutaneous Immunology and Allergy     Open Access  
Journal of Developmental Origins of Health and Disease     Hybrid Journal   (Followers: 2)
Journal of Endoluminal Endourology     Open Access  
Journal of Gastroenterology and Hepatology Research     Open Access   (Followers: 4)
Journal of General Internal Medicine     Hybrid Journal   (Followers: 23)
Journal of Hypertension     Hybrid Journal   (Followers: 14)
Journal of Infectious Diseases     Hybrid Journal   (Followers: 48)
Journal of Interdisciplinary Medicine     Open Access  
Journal of Internal Medicine     Hybrid Journal   (Followers: 11)
Journal of Liver : Disease & Transplantation     Hybrid Journal   (Followers: 7)
Journal of Medical Internet Research     Open Access   (Followers: 24)
Journal of Movement Disorders     Open Access   (Followers: 2)
Journal of Pain and Symptom Management     Hybrid Journal   (Followers: 46)
Journal of Pancreatic Cancer     Open Access  
Journal of Renal and Hepatic Disorders     Open Access  
Journal of Solid Tumors     Open Access   (Followers: 1)
Journal of Sports Medicine and Allied Health Sciences : Official Journal of the Ohio Athletic Trainers Association     Open Access   (Followers: 1)
Journal of the American Board of Family Medicine     Open Access   (Followers: 11)
Journal of the European Mosquito Control Association     Open Access  
Journal of Translational Internal Medicine     Open Access  
Jurnal Vektor Penyakit     Open Access  
La Revue de Medecine Interne     Full-text available via subscription   (Followers: 3)
Lege artis - Das Magazin zur ärztlichen Weiterbildung     Hybrid Journal   (Followers: 1)
Liver Cancer International     Open Access  
Liver Research     Open Access  
Molecular Diagnosis & Therapy     Hybrid Journal   (Followers: 3)
Molecular Therapy - Oncolytics     Open Access  
Multiple Sclerosis and Demyelinating Disorders     Open Access   (Followers: 7)
MYOPAIN. A journal of myofascial pain and fibromyalgia     Hybrid Journal   (Followers: 18)
Neuro-Oncology Advances     Open Access   (Followers: 1)
Neurobiology of Pain     Open Access   (Followers: 2)
Neurointervention     Open Access   (Followers: 6)
Neuromuscular Diseases     Open Access  
Nigerian Journal of Gastroenterology and Hepatology     Full-text available via subscription  
OA Alcohol     Open Access   (Followers: 5)
Oncological Coloproctology     Open Access  
Open Journal of Internal Medicine     Open Access  
Pleura and Peritoneum     Open Access  
Pneumo News     Full-text available via subscription  
Polish Archives of Internal Medicine     Full-text available via subscription   (Followers: 2)
Preventing Chronic Disease     Free   (Followers: 2)
Progress in Transplantation     Hybrid Journal   (Followers: 1)
Prostate International     Open Access   (Followers: 2)
Psychiatry and Clinical Psychopharmacology     Open Access   (Followers: 1)
Pulmonary Therapy     Open Access   (Followers: 2)
Quality of Life Research     Hybrid Journal   (Followers: 20)
Research and Practice in Thrombosis and Haemostasis     Open Access  
Revista Chilena de Fonoaudiología     Open Access   (Followers: 1)
Revista de la Sociedad Peruana de Medicina Interna     Open Access   (Followers: 4)
Revista del Instituto de Medicina Tropical     Open Access  
Revista Hispanoamericana de Hernia     Open Access   (Followers: 1)
Revista Médica Internacional sobre el Síndrome de Down     Full-text available via subscription   (Followers: 1)
Revista Virtual de la Sociedad Paraguaya de Medicina Interna     Open Access   (Followers: 1)
Romanian Journal of Diabetes Nutrition and Metabolic Diseases     Open Access   (Followers: 1)
Romanian Journal of Internal Medicine     Open Access  
Russian Journal of Child Neurology     Open Access   (Followers: 1)
Scandinavian Journal of Primary Health Care     Open Access   (Followers: 8)
Schlaf     Hybrid Journal  
Schmerzmedizin     Hybrid Journal  
Scientific Journal of the Foot & Ankle     Open Access   (Followers: 1)
SciMedicine Journal     Open Access   (Followers: 3)
SEMERGEN - Medicina de Familia     Full-text available via subscription   (Followers: 1)
The Journal of Critical Care Medicine     Open Access   (Followers: 9)
Therapeutic Advances in Chronic Disease     Open Access   (Followers: 8)
Therapeutic Advances in Musculoskeletal Disease     Hybrid Journal   (Followers: 6)
Thieme Case Report     Hybrid Journal   (Followers: 1)
Tijdschrift voor Urologie     Hybrid Journal  
Tissue Barriers     Hybrid Journal   (Followers: 1)
Transactions of the Royal Society of Tropical Medicine and Hygiene     Hybrid Journal   (Followers: 3)
Transgender Health     Open Access   (Followers: 3)
Trends in Anaesthesia and Critical Care     Full-text available via subscription   (Followers: 23)
US Cardiology Review     Open Access  
Vascular and Endovascular Review     Open Access   (Followers: 1)
Ожирение и метаболизм     Open Access  


Similar Journals
Journal Cover
Journal Prestige (SJR): 1.722
Citation Impact (citeScore): 3
Number of Followers: 3  

  This is an Open Access Journal Open Access journal
ISSN (Online) 2373-2822
Published by Society for Neuroscience Homepage  [2 journals]
  • The Home-Cage Automated Skilled Reaching Apparatus (HASRA): Individualized
           Training of Group-Housed Mice in a Single Pellet Reaching Task

    • Authors: Salameh, G; Jeffers, M. S, Wu, J, Pitney, J, Silasi, G.
      Abstract: The single pellet reaching task is commonly used in rodents to assess the acquisition of fine motor skill and recovery of function following nervous system injury. Although this task is useful for gauging skilled forelimb use in rodents, the process of training animals is labor intensive and variable across studies and labs. To address these limitations, we developed a single pellet reaching paradigm for training and testing group housed mice within their home cage. Mice enter a training compartment attached to the outside of the cage and retrieve millet seeds presented on a motorized pedestal that can be individually positioned to present seeds to either forelimb. To identify optimal training parameters, we compared task participation and success rates between groups of animals that were presented seeds at two different heights (floor vs mouth height) and at different intervals (fixed-time vs trial-based). The mouth height/fixed interval presentation style was most effective at promoting reaching behavior as all mice reached for seeds within 5 d. Using this paradigm, we assessed stroke-induced deficits in home-cage reaching. Following three weeks of baseline training, reaching success rate was ~40%, with most trials performed during the dark cycle. A forelimb motor cortex stroke significantly decreased interaction with presented seeds within the first 2 d and impaired reaching success rates for the first 7 d. Our data demonstrate that group-housed mice can be efficiently trained on a single pellet reaching task in the home cage and that this assay is sensitive to stroke induced motor impairments.
      Keywords: Novel Tools and Methods
      PubDate: 2020-10-21T09:34:05-07:00
      DOI: 10.1523/ENEURO.0242-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Frontal, Parietal, and Temporal Brain Areas Are Differentially Activated
           When Disambiguating Potential Objects of Joint Attention

    • Authors: Kraemer, P. M; Görner, M, Ramezanpour, H, Dicke, P. W, Thier, P.
      Abstract: Humans establish joint attention with others by following the other’s gaze. Previous work has suggested that a cortical patch (gaze-following patch, GFP) close to the posterior superior temporal sulcus (pSTS) may serve as a link between the extraction of the other’s gaze direction and the resulting shifts of attention, mediated by human lateral intraparietal area (hLIP). However, it is not clear how the brain copes with situations in which information on gaze direction alone is insufficient to identify the target object because more than one may lie along the gaze vector. In this fMRI study, we tested human subjects on a paradigm that allowed the identification of a target object based on the integration of the other’s gaze direction and information provided by an auditory cue on the relevant object category. Whereas the GFP activity turned out to be fully determined by the use of gaze direction, activity in hLIP reflected the total information needed to pinpoint the target. Moreover, in an exploratory analysis, we found that a region in the inferior frontal junction (IFJ) was sensitive to the total information on the target. An examination of the BOLD time courses in the three identified areas suggests functionally complementary roles. Although the GFP seems to primarily process directional information stemming from the other’s gaze, the IFJ may help to analyze the scene when gaze direction and auditory information are not sufficient to pinpoint the target. Finally, hLIP integrates both streams of information to shift attention to distinct spatial locations.
      Keywords: Cognition and Behavior
      PubDate: 2020-10-21T09:30:39-07:00
      DOI: 10.1523/ENEURO.0437-19.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Strategic and Non-Strategic Semantic Expectations Hierarchically Modulate
           Neural Processing

    • Authors: Vidal-Gran, C; Sokoliuk, R, Bowman, H, Cruse, D.
      Abstract: Perception is facilitated by a hierarchy of expectations generated from context and prior knowledge. In auditory processing, violations of local (within-trial) expectations elicit a mismatch negativity (MMN), while violations of global (across-trial) expectations elicit a later positive component (P300). This result is taken as evidence of prediction errors ascending through the expectation hierarchy. However, in language comprehension, there is no evidence that violations of semantic expectations across local-global levels similarly elicit a sequence of hierarchical error signals, thus drawing into question the putative link between event-related potentials (ERPs) and prediction errors. We investigated the neural basis of such hierarchical expectations of semantics in a word-pair priming paradigm. By manipulating the overall proportion of related or unrelated word-pairs across the task, we created two global contexts that differentially encouraged strategic use of primes. Across two experiments, we replicated behavioral evidence of greater priming in the high validity context, reflecting strategic expectations of upcoming targets based on "global" context. In our preregistered EEG analyses, we observed a "local" prediction error ERP effect (i.e., semantic priming) ~250 ms post-target, which, in exploratory analyses, was followed 100 ms later by a signal that interacted with the global context. However, the later effect behaved in an apredictive manner, i.e., was most extreme for fulfilled expectations, rather than violations. Our results are consistent with interpretations of early ERPs as reflections of prediction error and later ERPs as processes related to conscious access and in support of task demands.
      Keywords: Cognition and Behavior
      PubDate: 2020-10-19T09:45:37-07:00
      DOI: 10.1523/ENEURO.0229-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Differential Modulation of Ventral Tegmental Area Circuits by the
           Nociceptin/Orphanin FQ System

    • Authors: Driscoll, J. R; Wallace, T. L, Mansourian, K. A, Martin, W. J, Margolis, E. B.
      Abstract: The neuropeptide nociceptin/orphanin FQ (N/OFQ) can be released by stressors and is associated with disorders of emotion regulation and reward processing. N/OFQ and its receptor, NOP, are enriched in dopaminergic pathways, and intra-ventricular agonist delivery decreases dopamine levels in the dorsal striatum, nucleus accumbens (NAc), and ventral tegmental area (VTA). We used whole-cell electrophysiology in acute rat midbrain slices to investigate synaptic actions of N/OFQ. N/OFQ was primarily inhibitory, causing outward currents in both immunocytochemically identified dopaminergic (tyrosine hydroxylase positive (TH(+))) and non-dopaminergic (TH(–)) VTA neurons; effect at 1 μm: 20 ± 4 pA. Surprisingly, this effect was mediated by augmentation of postsynaptic GABAAR currents, unlike the substantia nigra pars compacta (SNc), where the N/OFQ-induced outward currents were K+ channel dependent. A smaller population, 17% of all VTA neurons, responded to low concentrations of N/OFQ with inward currents (10 nm: –11 ± 2 pA). Following 100 nm N/OFQ, the response to a second N/OFQ application was markedly diminished in VTA neurons (14 ± 10% of first response) but not in SNc neurons (90 ± 20% of first response). N/OFQ generated outward currents in medial prefrontal cortex (mPFC)-projecting VTA neurons, but inward currents in a subset of posterior anterior cingulate cortex (pACC)-projecting VTA neurons. While N/OFQ inhibited NAc-projecting VTA cell bodies, it had little effect on electrically or optogenetically evoked terminal dopamine release in the NAc measured ex vivo with fast scan cyclic voltammetry (FSCV). These results extend our understanding of the N/OFQ system in brainstem circuits implicated in many neurobehavioral disorders.
      Keywords: Integrative Systems
      PubDate: 2020-10-19T09:45:37-07:00
      DOI: 10.1523/ENEURO.0376-19.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Upregulation of nAChRs and Changes in Excitability on VTA Dopamine and
           GABA Neurons Correlates to Changes in Nicotine-Reward-Related Behavior

    • Authors: Akers, A. T; Cooper, S. Y, Baumgard, Z. J, Casinelli, G. P, Avelar, A. J, Henderson, B. J.
      Abstract: Previous reports indicate that nicotine reward is mediated through α4β2*, α6β2*, and α4α6β2* nicotinic acetylcholine receptors (nAChRs; * indicates that additional nAChR subunits may be present). Little is known about α4α6β2* nAChR involvement in reward and reinforcement because of a lack of methods that allow the direct investigation of this particular nAChR subtype. Here, we use male and female mice that contain α4-mCherry and α6-GFP nAChR subunits to show that concentrations of nicotine sufficient to evoke reward-related behavior robustly upregulate α4* and α4α6* nAChRs on midbrain dopamine (DA) and GABA neurons. Furthermore, the extent of α4α6* nAChR upregulation on ventral tegmental area (VTA) DA neurons aligns with the magnitude of nicotine reward-related behavior. We also show that the upregulation of nAChRs is accompanied by a functional change in firing frequency of both DA and GABA neurons in the VTA that is directly linked to nicotine reward-related behavior.
      Keywords: Disorders of the Nervous System
      PubDate: 2020-10-15T09:31:57-07:00
      DOI: 10.1523/ENEURO.0189-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Doublecortin-Like Is Implicated in Adult Hippocampal Neurogenesis and in
           Motivational Aspects to Escape from an Aversive Environment in Male Mice

    • Authors: Saaltink, D.-J; van Zwet, E. W, Vreugdenhil, E.
      Abstract: Doublecortin (DCX)-like (DCL) is a microtubule (MT)-associated protein (MAP) that is highly homologous to DCX and is crucially involved in embryonic neurogenesis. Here, we have investigated the in vivo role of DCL in adult hippocampal neurogenesis by generating transgenic mice producing inducible shRNA molecules that specifically target DCL but no other splice variants produced by the DCLK gene. DCL knock-down (DCL-KD) resulted in a significant increase in the number of proliferating BrdU+ cells in the subgranular zone (SGZ) 1 d after BrdU administration. However, the number of surviving newborn adult NeuN+/BrdU+ neurons are significantly decreased when inspected four weeks after BrdU administration suggesting a blockade of neuronal differentiation after DCL-KD. In line with this, we observed an increase in the number of proliferating cells, but a significant decrease in postmitotic DCX+ cells that are characterized by long dendrites spanning all dentate gyrus layers. Behavioral analysis showed that DCL-KD strongly extended the escape latency of mice on the circular hole board (CHB) but did not affect other aspects of this behavioral task. Together, our results indicate a function for DCL in adult neurogenesis and in the motivation to escape from an aversive environment. In contrast to DCX, its pivotal role in the maturation of postmitotic neuronal progenitor cells (NPCs) marks DCL as a genuine adult neurogenesis indicator in the hippocampus.
      Keywords: Cognition and Behavior
      PubDate: 2020-10-15T09:31:57-07:00
      DOI: 10.1523/ENEURO.0324-19.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Cortical Presynaptic Boutons Progressively Engulf Spinules as They Mature

    • Authors: Campbell, C; Lindhartsen, S, Knyaz, A, Erisir, A, Nahmani, M.
      Abstract: Despite decades of discussion in the neuroanatomical literature, the role of the synaptic "spinule" in synaptic development and function remains elusive. Canonically, spinules are finger-like projections that emerge from postsynaptic spines and can become enveloped by presynaptic boutons. When a presynaptic bouton encapsulates a spinule in this manner, the membrane apposition between the spinule and surrounding bouton can be significantly larger than the membrane interface at the synaptic active zone. Hence, spinules may represent a mechanism for extrasynaptic neuronal communication and/or may function as structural "anchors" that increase the stability of cortical synapses. Yet despite their potential to impact synaptic function, we have little information on the percentages of developing and adult cortical bouton populations that contain spinules, the percentages of these cortical spinule-bearing boutons (SBBs) that contain spinules from distinct neuronal/glial origins, or whether the onset of activity or cortical plasticity are correlated with increased prevalence of cortical SBBs. Here, we employed 2D and 3D electron microscopy to determine the prevalence of spinules in excitatory presynaptic boutons at key developmental time points in the primary visual cortex (V1) of female and male ferrets. We find that the prevalence of SBBs in V1 increases across postnatal development, such that ~25% of excitatory boutons in late adolescent ferret V1 contain spinules. In addition, we find that a majority of spinules within SBBs at later developmental time points emerge from postsynaptic spines and adjacent boutons/axons, suggesting that synaptic spinules may enhance synaptic stability and allow for axo-axonal communication in mature sensory cortex.
      Keywords: Development
      PubDate: 2020-10-15T09:31:57-07:00
      DOI: 10.1523/ENEURO.0426-19.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Effects of Neuronic Shutter Observed in the EEG Alpha Rhythm

    • Authors: Alexander, K. E; Estepp, J. R, Elbasiouny, S. M.
      Abstract: The posterior alpha (α) rhythm, seen in human electroencephalogram (EEG), is posited to originate from cycling inhibitory/excitatory states of visual relay cells in the thalamus. These cycling states are thought to lead to oscillating visual sensitivity levels termed the "neuronic shutter effect." If true, perceptual performance should be predictable by observed α phase (of cycling inhibitory/excitatory states) relative to the timeline of afferentiation onto the visual cortex. Here, we tested this hypothesis by presenting contrast changes at near perceptual threshold intensity through closed eyelids to 20 participants (balanced for gender) during times of spontaneous α oscillations. To more accurately and rigorously test the shutter hypothesis than ever before, α rhythm phase and amplitude were calculated relative to each individual’s retina-to-primary visual cortex (V1) conduction delay, estimated from the individual’s C1 visual-evoked potential (VEP) latency. Our results show that stimulus observation rates (ORs) are greater at a trough than a peak of the posterior α rhythm when phase is measured at the individual’s conduction delay relative to stimulus onset. Specifically, the optimal phase for stimulus observation was found to be 272.41°, where ORs are 20.96% greater than the opposing phase of 92.41°. The perception-phase relationship is modulated by α rhythm amplitude and is not observed at lower amplitude oscillations. Collectively, these results provide support to the "neuronic shutter" hypothesis and demonstrate a phase and timing relationship consistent with the theory that cycling excitability in the thalamic relay cells underly posterior α oscillations.
      Keywords: Cognition and Behavior
      PubDate: 2020-10-09T09:46:10-07:00
      DOI: 10.1523/ENEURO.0171-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Variable Interhemispheric Asymmetry in Layer V of the Supplementary Motor
           Area following Cervical Hemisection in Adult Macaque Monkeys

    • Authors: Contestabile, A; Colangiulo, R, Lucchini, M, Rouiller, E. M, Schmidlin, E.
      Abstract: Motor cortical areas from both hemispheres play a role during functional recovery after a unilateral spinal cord injury (SCI). However, little is known about the morphologic and phenotypical differences that a SCI could trigger in corticospinal (CS) neurons of the ipsilesional and contralesional hemisphere. Using an SMI-32 antibody which specifically labeled pyramidal neurons in cortical Layers V, we investigated the impact of a unilateral cervical cord lesion on the rostral part (F6) and caudal part (F3) of the supplementary motor area (SMA) in both hemispheres of eight adult macaque monkeys compared with four intact control monkeys. We observed in F3 (but not in F6) interindividual variable and adaptive interhemispheric asymmetries of SMI-32-positive Layer V neuronal density and dendritic arborization, which are strongly correlated with the extent of the SCI as well as the duration of functional recovery, but not with the extent (percentage) of functional recovery.
      Keywords: Disorders of the Nervous System
      PubDate: 2020-10-09T09:46:10-07:00
      DOI: 10.1523/ENEURO.0280-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Disrupted Coordination of Hypoglossal Motor Control in a Mouse Model of
           Pediatric Dysphagia in DiGeorge/22q11.2 Deletion Syndrome

    • Authors: Wang, X; Popratiloff, A, Motahari, Z, LaMantia, A.-S, Mendelowitz, D.
      Abstract: We asked whether the physiological and morphologic properties of hypoglossal motor neurons (CNXII MNs) that innervate protruder or retractor tongue muscles are disrupted in neonatal LgDel mice that carry a heterozygous deletion parallel to that associated with DiGeorge/22q11.2 deletion syndrome (22q11.2DS). Disrupted coordination of tongue movement in LgDel mouse pups may contribute to suckling, feeding, and swallowing (S/F/S) disruptions that parallel pediatric dysphagia in infants and toddlers with 22q11.2DS. Using an in vitro rhythmically active medullary slice preparation, we found spontaneous firing as well as IPSC frequency differed significantly in neonatal LgDel versus wild-type (WT) protruder and retractor CNXII MNs that were identified by retrograde tracing from their target muscles. In response to respiration-related activity, initiation and decay of transiently increased firing in WT protruder MNs is delayed in LgDel, accompanied by altered excitatory/inhibitory (E/I) balance. In addition, LgDel retractor MNs have a transient increase in firing with diminished IPSC frequency that is not seen in WT. There were no significant differences in cell body volume of either XII class in WT and LgDel. Sholl analysis showed the total numbers of dendritic intersections (at 50- and 90-μm radii from the cell soma) were significantly greater for LgDel versus WT retractor MNs. Thus, the physiological, synaptic and cellular properties of distinct classes of CNXII MNs that coordinate tongue movement in neonatal WT mice are altered in LgDel. Such changes could contribute to sub-optimal coordination of S/F/S that underlies pediatric dysphagia in 22q11.2DS.
      Keywords: Integrative Systems
      PubDate: 2020-10-09T09:46:10-07:00
      DOI: 10.1523/ENEURO.0520-19.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Activation of Subthalamic Nucleus Stop Circuit Disrupts Cognitive

    • Authors: Heston, J; Friedman, A, Baqai, M, Bavafa, N, Aron, A. R, Hnasko, T. S.
      Abstract: Much evidence supports a fundamental role for the subthalamic nucleus (STN) in rapidly stopping behavior when a stop signal or surprising event occurs, but the extent to which the STN may be involved in stopping cognitive processes is less clear. Here, we used an optogenetic approach to control STN activity in a delayed-match-to-position (DMTP) task where mice had to recall a response location after a delay. We first demonstrated that a surprising event impaired performance by both slowing the latency to respond and increasing the rate of errors. We next showed that these effects could be mimicked by brief optogenetic activation of the STN. Further, inhibiting STN during surprise blocked surprise-induced slowing, although without changing surprise-induced errors. These data are consistent with the hypothesis that STN is recruited by surprise to slow responding and that this can also interrupt cognitive processes. Under normal conditions STN-mediated stopping of behavior may slow or stop ongoing cognition to facilitate cognitive reorienting and adaptive responses to unexpected sensory information, but when malfunctioning, it could produce pathologies related to over-rigidity or increased distractibility.
      Keywords: Cognition and Behavior
      PubDate: 2020-10-07T09:30:27-07:00
      DOI: 10.1523/ENEURO.0159-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Distinct Age-Dependent C Fiber-Driven Oscillatory Activity in the Rat
           Somatosensory Cortex

    • Authors: Chang, P; Fabrizi, L, Fitzgerald, M.
      Abstract: When skin afferents are activated, the sensory signals are transmitted to the spinal cord and eventually reach the primary somatosensory cortex (S1), initiating the encoding of the sensory percept in the brain. While subsets of primary afferents mediate specific somatosensory information from an early age, the subcortical pathways that transmit this information undergo striking changes over the first weeks of life, reflected in the gradual emergence of specific sensory behaviors. We therefore hypothesized that this period is associated with differential changes in the encoding of incoming afferent volleys in S1. To test this, we compared S1 responses to A fiber skin afferent stimulation and A + C skin afferent fiber stimulation in lightly anaesthetized male rats at postnatal day (P)7, P14, P21, and P30. Differences in S1 activity following A and A + C fiber stimulation changed dramatically over this period. At P30, A + C fiber stimulation evoked significantly larger , β, and α energy increases compared with A fiber stimulation alone. At younger ages, the changes in S1 oscillatory activity evoked by the two afferent volleys were not significantly different. Silencing TRPV1+ C fibers with QX-314 significantly reduced the and β S1 oscillatory energy increases evoked by A + C fibers, at P30 and P21, but not at younger ages. Thus, C fibers differentially modulate S1 oscillatory activity only from the third postnatal week, well after the functional maturation of the somatosensory cortex. This age-related change in afferent evoked S1 oscillatory activity may underpin the maturation of sensory discrimination in the developing brain.
      Keywords: Sensory and Motor Systems
      PubDate: 2020-10-07T09:30:26-07:00
      DOI: 10.1523/ENEURO.0036-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Parallel Lemniscal and Non-Lemniscal Sources Control Auditory Responses in
           the Orbitofrontal Cortex (OFC)

    • Authors: Srivastava, H. K; Bandyopadhyay, S.
      Abstract: The orbitofrontal cortex (OFC) controls flexible behavior through stimulus value updating based on stimulus outcome associations, allowing seamless navigation in dynamic sensory environments with changing contingencies. Sensory cue driven responses, primarily studied through behavior, exist in the OFC. However, OFC neurons’ sensory response properties, particularly auditory, are unknown in the mouse, a genetically tractable animal. We show that mouse OFC single neurons have unique auditory response properties showing pure oddball detection and long timescales of adaptation resulting in stimulus-history dependence. Further, we show that OFC auditory responses are shaped by two parallel sources in the auditory thalamus, lemniscal and non-lemniscal. The latter underlies a large component of the observed oddball detection and additionally controls persistent activity in the OFC through the amygdala. The deviant selectivity can serve as a signal for important changes in the auditory environment. Such signals, if coupled with persistent activity, obtained by disinhibitory control from the non-lemniscal auditory thalamus or amygdala, will allow for associations with a delayed outcome related signal, like reward prediction error, and potentially forms the basis of updating stimulus outcome associations in the OFC. Thus, the baseline sensory responses allow the behavioral requirement-based response modification through relevant inputs from other structures related to reward, punishment, or memory. Thus, alterations in these responses in neurologic disorders can lead to behavioral deficits.
      Keywords: Sensory and Motor Systems
      PubDate: 2020-10-07T09:30:26-07:00
      DOI: 10.1523/ENEURO.0121-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Regional Activity in the Rat Anterior Cingulate Cortex and Insula during
           Persistence and Quitting in a Physical-Effort Task

    • Authors: Porter, B. S; Li, K, Hillman, K. L.
      Abstract: As animals carry out behaviors, particularly costly ones, they must constantly assess whether or not to persist in the behavior or quit. The anterior cingulate cortex (ACC) has been shown to assess the value of behaviors and to be especially sensitive to physical effort costs. Complimentary to these functions, the insula is thought to represent the internal state of the animal including factors such as hunger, thirst, and fatigue. Using a novel weight-lifting task for rats, we characterized the local field potential (LFP) activity of the ACC and anterior insula (AI) during effort expenditure. In the task, male rats are challenged to work for sucrose reward, which costs progressively more effort over time to obtain. Rats are able to quit the task at any point. We found modest shifts in LFP theta (7–9 Hz) activity as the task got progressively more difficult in terms of absolute effort expenditure. However, when the LFP data were analyzed based on the relative progress of the rat toward quitting the task, substantial shifts in LFP power in the theta and gamma (55–100 Hz) frequency bands were observed in ACC and AI. Both ACC and AI theta power decreased as the rats got closer to quitting, while ACC and AI gamma power increased. Furthermore, coherency between ACC and AI in the delta (2–4 Hz) range shifted alongside the performance state of the rat. Overall, we show that ACC and AI LFP activity changes correlate to the relative performance state of rats in an effort-based task.
      Keywords: Cognition and Behavior
      PubDate: 2020-10-07T09:30:26-07:00
      DOI: 10.1523/ENEURO.0243-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Interaction of Fear Conditioning with Eyeblink Conditioning Supports the
           Sensory Gating Hypothesis of the Amygdala in Men

    • Authors: Inoue, L; Ernst, T. M, Ferber, I. I, Merz, C. J, Timmann, D, Batsikadze, G.
      Abstract: Inhibition of the amygdala slows down acquisition of conditioned eyeblink responses (CRs). Based on the two-stage or two-factor theory of aversive conditioning, amygdala-dependent conditioned fear is a necessary prerequisite to acquire eyeblink CRs but is no longer needed after eyeblink CRs are attained. According to the sensory gating hypothesis of the amygdala, on the other hand, the amygdala modulates the salience of unconditioned stimuli (USs) and conditioned stimuli (CSs) in eyeblink conditioning. We tested these two opposing assumptions in five groups of 20 young and healthy men. On day 1, three groups underwent fear acquisition training followed by acquisition of eyeblink CRs. On the next day (day 2), extinction was tested. In group 1, fear and eyeblink extinction trials overlapped; in group 2, fear and eyeblink extinction trials alternated; and in group 3, fear extinction trials were followed by eyeblink extinction trials. Groups 4 and 5 were control conditions testing fear and eyeblink conditioning only. Preceding fear acquisition training facilitated acquisition of conditioned eyeblinks. Concomitant fear extinction impeded extinction of eyeblink CRs, which was accompanied by increased autonomic responses. Fear extinction, however, was not significantly altered by concomitant eyeblink extinction. Recall of fear CRs on day 2 was facilitated in group 1, suggesting additive response summation. Findings are difficult to explain with the two-stage theory of aversive conditioning, which predicts the suppression of conditioned fear once conditioned eyeblinks are acquired. Facilitated acquisition and impeded extinction of eyeblink CRs, however, are in accordance with the sensory-gating hypothesis of the amygdala.
      Keywords: Cognition and Behavior
      PubDate: 2020-10-01T09:30:28-07:00
      DOI: 10.1523/ENEURO.0128-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • TGF{beta}1 Induces Axonal Outgrowth via ALK5/PKA/SMURF1-Mediated
           Degradation of RhoA and Stabilization of PAR6

    • Authors: Kaiser, J; Maibach, M, Piovesana, E, Salpeter, I, Escher, N, Ormen, Y, Schwab, M. E.
      Abstract: Transforming growth factor (TGF)β1 has repeatedly been associated with axonal regeneration and recovery after injury to the CNS. We found TGFβ1 upregulated in the stroke-denervated mouse spinal cord after ischemic injury to the motor cortex as early as 4 d postinjury (dpi) and persisting up to 28 dpi. Given the potential role of TGFβ1 in structural plasticity and functional recovery after stroke highlighted in several published studies, we investigated its downstream signaling in an in vitro model of neurite outgrowth. We found that in this model, TGFβ1 rescues neurite outgrowth under growth inhibitory conditions via the canonical TGFβR2/ALK5 signaling axis. Thereby, protein kinase A (PKA)-mediated phosphorylation of the E3 ubiquitin ligase SMURF1 induces a switch of its substrate preference from PAR6 to the Ras homolog A (RhoA), in this way enhancing outgrowth on the level of the cytoskeleton. This proposed mechanism of TGFβ1 signaling could underly the observed increase in structural plasticity after stroke in vivo as suggested by the temporal and spatial expression of TGFβ1. In accordance with previous publications, this study corroborates the potential of TGFβ1 and associated signaling cascades as a target for future therapeutic interventions to enhance structural plasticity and functional recovery for stroke patients.
      Keywords: Disorders of the Nervous System
      PubDate: 2020-09-29T09:30:23-07:00
      DOI: 10.1523/ENEURO.0104-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Dissecting the Tectal Output Channels for Orienting and Defense Responses

    • Authors: Isa, K; Sooksawate, T, Kobayashi, K, Kobayashi, K, Redgrave, P, Isa, T.
      Abstract: Electrical stimulation and lesion experiments in 1980’s suggested that the crossed descending pathway from the deeper layers of superior colliculus (SCd) controls orienting responses, while the uncrossed pathway mediates defense-like behavior. To overcome the limitation of these classical studies and explicitly dissect the structure and function of these two pathways, we performed selective optogenetic activation of each pathway in male mice with channelrhodopsin 2 (ChR2) expression by Cre driver using double viral vector techniques. Brief photostimulation of the crossed pathway evoked short latency contraversive orienting-like head turns, while extended stimulation induced body turn responses. In contrast, stimulation of the uncrossed pathway induced short-latency upward head movements followed by longer-latency defense-like behaviors including retreat and flight. The novel discovery was that while the evoked orienting responses were stereotyped, the defense-like responses varied considerably depending on the environment, suggesting that uncrossed output can be influenced by top-down modification of the SC or its target areas. This further suggests that the connection of the SCd-defense system with non-motor, affective and cognitive structures. Tracing the whole axonal trajectories of these two pathways revealed existence of both ascending and descending branches targeting different areas in the thalamus, midbrain, pons, medulla, and/or spinal cord, including projections which could not be detected in the classical studies; the crossed pathway has some ipsilaterally descending collaterals and the uncrossed pathway has some contralaterally descending collaterals. Some of the connections might explain the context-dependent modulation of the defense-like responses. Thus, the classical views on the tectal output systems are updated.
      Keywords: Sensory and Motor Systems
      PubDate: 2020-09-29T09:30:23-07:00
      DOI: 10.1523/ENEURO.0271-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Aging Effects and Test-Retest Reliability of Inhibitory Control for
           Saccadic Eye Movements

    • Authors: Płomecka, M. B; Baranczuk-Turska, Z, Pfeiffer, C, Langer, N.
      Abstract: Neuropsychological studies indicate that healthy aging is associated with a decline of inhibitory control of attentional and behavioral systems. A widely accepted measure of inhibitory control is the antisaccade task that requires both the inhibition of a reflexive saccadic response toward a visual target and the initiation of a voluntary eye movement in the opposite direction. To better understand the nature of age-related differences in inhibitory control, we evaluated antisaccade task performance in 78 younger (20–35 years) and 78 older (60–80 years) participants. In order to provide reliable estimates of inhibitory control for individual subjects, we investigated test–retest reliability of the reaction time, error rate, saccadic gain, and peak saccadic velocity and further estimated latent, not directly observable processed contributing to changes in the antisaccade task execution. The intraclass correlation coefficients (ICCs) for an older group of participants emerged as good to excellent for most of our antisaccade task measures. Furthermore, using Bayesian multivariate models, we inspected age-related differences in the performances of healthy younger and older participants. The older group demonstrated higher error rates, longer reaction times, significantly more inhibition failures, and late prosaccades as compared with young adults. The consequently lower ability of older adults to voluntarily inhibit saccadic responses has been interpreted as an indicator of age-related inhibitory control decline. Additionally, we performed a Bayesian model comparison of used computational models and concluded that the Stochastic Early Reaction, Inhibition and Late Action (SERIA) model explains our data better than PRO-Stop-Antisaccade (PROSA) that does not incorporate a late decision process.
      Keywords: Registered Reports, Cognition and Behavior
      PubDate: 2020-09-29T09:30:23-07:00
      DOI: 10.1523/ENEURO.0459-19.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Fear Deficits in Hypomyelinated Tppp Knock-Out Mice

    • Authors: Nguyen, H; Meservey, L. M, Ishiko-Silveria, N, Zhou, M, Huang, T.-T, Fu, M.-m.
      Abstract: Oligodendrocytes in the central nervous system (CNS) produce myelin sheaths that insulate axons to facilitate efficient electrical conduction. These myelin sheaths contain lamellar microtubules that enable vesicular transport into the inner sheath. Mechanistically, oligodendrocytes rely on Golgi outpost organelles and the associated protein tubulin polymerization promoting protein (TPPP) to nucleate or form new microtubules outside of the cell body. Consequently, elongation of lamellar microtubules is defective in Tppp knock-out (KO) mice, which have thinner and shorter myelin sheaths. We now explore the behavioral phenotypes of Tppp KO mice using a number of different assays. In open-field assays, Tppp KO mice display similar activity levels and movement patterns as wild-type mice, indicating that they do not display anxiety behavior. However, Tppp KO mice lack fear responses by two types of assays, traditional fear-conditioning assays and looming fear assays, which test for innate fear responses. Deficits in fear conditioning, which is a memory-dependent task, as well as in spatial memory tests, support possible short-term memory defects in Tppp KO mice. Together, our experiments indicate a connection between CNS myelination and behavioral deficits.
      Keywords: Neuronal Excitability
      PubDate: 2020-09-28T09:33:33-07:00
      DOI: 10.1523/ENEURO.0170-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Resolving the Connectome, Spectrally-Specific Functional Connectivity
           Networks and Their Distinct Contributions to Behavior

    • Authors: Becker, R; Hervais-Adelman, A.
      Abstract: The resting human brain exhibits spontaneous patterns of activity that reflect features of the underlying neural substrate. Examination of interareal coupling of resting-state oscillatory activity has revealed that the brain’s resting activity is composed of functional networks, whose topographies differ depending on oscillatory frequency, suggesting a role for carrier frequency as a means of creating multiplexed, or functionally segregated, communication channels between brain areas. Using canonical correlation analysis (CCA), we examined spectrally resolved resting-state connectivity patterns derived from magnetoencephalography (MEG) recordings to determine the relationship between connectivity intrinsic to different frequency channels and a battery of over a hundred behavioral and demographic indicators, in a group of 89 young healthy participants. We demonstrate that each of the classical frequency bands in the range 1–40 Hz (, , α, β, and ) delineates a subnetwork that is behaviorally relevant, spatially distinct, and whose expression is either negatively or positively predictive of individual traits, with the strongest link in the α-band being negative and networks oscillating at different frequencies, such as , β, and carrying positive function.
      Keywords: Cognition and Behavior
      PubDate: 2020-09-23T09:30:18-07:00
      DOI: 10.1523/ENEURO.0101-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • The SUMO Conjugase Ubc9 Protects Dopaminergic Cells from Cytotoxicity and
           Enhances the Stability of {alpha}-Synuclein in Parkinsons Disease Models

    • Authors: Verma, D. K; Ghosh, A, Ruggiero, L, Cartier, E, Janezic, E, Williams, D, Jung, E.-G, Moore, M, Seo, J. B, Kim, Y.-H.
      Abstract: Small ubiquitin-like modifier (SUMO) is a widespread regulatory mechanism of post-translational modification (PTM) that induces rapid and reversible changes in protein function and stability. Using SUMO conjugase Ubc9-overexpressing or knock-down cells in Parkinson’s disease (PD) models, we demonstrate that SUMOylation protects dopaminergic cells against MPP+ or preformed fibrils (PFFs) of α-synuclein (α-syn)-induced toxicities in cell viability and cytotoxicity assays. In the mechanism of protection, Ubc9 overexpression significantly suppressed the MPP+ or PFF-induced reactive oxygen species (ROS) generation, while Ubc9-RNAi enhanced the toxicity-induced ROS production. Further, PFF-mediated protein aggregation was exacerbated by Ubc9-RNAi in thioflavin T staining, compared with NC1 controls. In cycloheximide (Chx)-based protein stability assays, higher protein level of α-syn was identified in Ubc9-enhanced green fluorescent protein (EGFP) than in EGFP cells. Since there was no difference in endogenous mRNA levels of α-syn between Ubc9 and EGFP cells in quantitative real-time PCR (qRT-PCR), we assessed the mechanisms of SUMO-mediated delayed α-syn degradation via MG132, proteasomal inhibitor, and PMA, lysosomal degradation inducer. Ubc9-mediated SUMOylated α-syn avoided PMA-induced lysosomal degradation because of its high solubility. Our results suggest that Ubc9 enhances the levels of SUMO1 and ubiquitin on α-syn and interrupts SUMO1 removal from α-syn. In immunohistochemistry, dopaminergic axon tips in the striatum and cell bodies in the substantia nigra from Ubc9-overexpressing transgenic mice were protected from MPTP toxicities compared with wild-type (WT) siblings. Our results support that SUMOylation can be a regulatory target to protect dopaminergic neurons from oxidative stress and protein aggregation, with the implication that high levels of SUMOylation in dopaminergic neurons can prevent the pathologic progression of PD.
      Keywords: Disorders of the Nervous System
      PubDate: 2020-09-23T09:30:18-07:00
      DOI: 10.1523/ENEURO.0134-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • No Evidence for an Object Working Memory Capacity Benefit with Extended
           Viewing Time

    • Authors: Quirk, C; Adam, K. C. S, Vogel, E. K.
      Abstract: Visual working memory is the ability to hold visual information temporarily in mind. A key feature of working memory is its starkly limited capacity, such that only a few simple items can be remembered at once. Prior work has shown that this capacity limit cannot be circumvented by providing additional encoding time, whether providing just 200 ms or up to 1300 ms, capacity is still limited to only three to four items. In contrast, Brady et al. (2016) hypothesized that real-world objects, but not simple items used in prior research, benefit from additional encoding time and are not subject to traditional capacity limits. They supported this hypothesis with results from both behavior and the contralateral delay activity (CDA), an EEG marker of working memory storage, and concluded that familiar, complex stimuli are necessary to observe encoding time effects. Here, we conducted three replications of Brady et al.’s key manipulation with a larger number of human participants and more trials per condition. We failed to replicate their primary behavioral result (objects benefit more than colors from additional encoding time) and failed to observe an object-specific increase in the CDA. Instead, we found that encoding time benefitted both simple color items and real-world objects, in contrast to both the findings by Brady et al., and some prior work on this topic. Overall, we observed no support for the hypothesis that real-world objects have a different capacity than colored squares. We discuss the implications of our findings for theories of visual working memory (VWM).
      Keywords: Cognition and Behavior
      PubDate: 2020-09-23T09:30:18-07:00
      DOI: 10.1523/ENEURO.0150-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Experience-Dependent Counselor-Client Brain Synchronization during
           Psychological Counseling

    • Authors: Zhang, Y; Meng, T, Yang, Y, Hu, Y.
      Abstract: The role of the counselor’s experience in building an alliance with the clients remains controversial. Recently, the expanding nascent studies on interpersonal brain synchronization (IBS) using functional near-infrared spectroscopy (fNIRS) on human subjects have hinted at the possible neural substrates underlying the relationship qualities between the counselor-client dyads. Our study assessed the clients’ self-report working alliance (WA) as well as simultaneously measured IBS by fNIRS in 14 experienced versus 16 novice counselor-client dyads during the first integrative-orientation psychological counseling session. We observed that synchronous brain activity patterns were elicited from the right temporo-parietal junction (rTPJ) across counselor-client dyads. Furthermore, such IBS, together with alliance quality, was especially evident when counselors had more psychotherapy experience. Time-lagged counselor-client brain synchronization might co-vary with the alliance (goal component) when the client’s brain activity preceded that of the counselor. These findings favor the notion that the IBS between counselor-client associated with the WA is an experience-dependent phenomenon, suggesting that a potential adaptive mechanism is embedded in psychological counseling.
      Keywords: Cognition and Behavior
      PubDate: 2020-09-23T09:30:18-07:00
      DOI: 10.1523/ENEURO.0236-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • {mu}-Opioid Receptors on Distinct Neuronal Populations Mediate Different
           Aspects of Opioid Reward-Related Behaviors

    • Authors: Severino, A. L; Mittal, N, Hakimian, J. K, Velarde, N, Minasyan, A, Albert, R, Torres, C, Romaneschi, N, Johnston, C, Tiwari, S, Lee, A. S, Taylor, A. M, Gaveriaux-Ruff, C, Kieffer, B. L, Evans, C. J, Cahill, C. M, Walwyn, W. M.
      Abstract: μ-Opioid receptors (MORs) are densely expressed in different brain regions known to mediate reward. One such region is the striatum where MORs are densely expressed, yet the role of these MOR populations in modulating reward is relatively unknown. We have begun to address this question by using a series of genetically engineered mice based on the Cre recombinase/loxP system to selectively delete MORs from specific neurons enriched in the striatum: dopamine 1 (D1) receptors, D2 receptors, adenosine 2a (A2a) receptors, and choline acetyltransferase (ChAT). We first determined the effects of each deletion on opioid-induced locomotion, a striatal and dopamine-dependent behavior. We show that MOR deletion from D1 neurons reduced opioid (morphine and oxycodone)-induced hyperlocomotion, whereas deleting MORs from A2a neurons resulted in enhanced opioid-induced locomotion, and deleting MORs from D2 or ChAT neurons had no effect. We also present the effect of each deletion on opioid intravenous self-administration. We first assessed the acquisition of this behavior using remifentanil as the reinforcing opioid and found no effect of genotype. Mice were then transitioned to oxycodone as the reinforcer and maintained here for 9 d. Again, no genotype effect was found. However, when mice underwent 3 d of extinction training, during which the drug was not delivered, but all cues remained as during the maintenance phase, drug-seeking behavior was enhanced when MORs were deleted from A2a or ChAT neurons. These findings show that these selective MOR populations play specific roles in reward-associated behaviors.
      Keywords: Cognition and Behavior
      PubDate: 2020-09-21T09:30:16-07:00
      DOI: 10.1523/ENEURO.0146-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Dynamic Contextual Modulation in Superior Colliculus of Awake Mouse

    • Authors: De Franceschi, G; Solomon, S. G.
      Abstract: The responses of neurons in the visual pathway depend on the context in which a stimulus is presented. Responses to predictable stimuli are usually suppressed, highlighting responses to unexpected stimuli that might be important for behavior. Here, we established how context modulates the response of neurons in the superior colliculus (SC), a region important in orienting toward or away from visual stimuli. We made extracellular recordings from single units in the superficial layers of SC in awake mice. We found strong suppression of visual response by spatial context (surround suppression) and temporal context (adaptation). Neurons showing stronger surround suppression also showed stronger adaptation effects. In neurons where it was present, surround suppression was dynamic and was reduced by adaptation. Adaptation’s effects further revealed two components to surround suppression: one component that was weakly tuned for orientation and adaptable, and another component that was more strongly tuned but less adaptable. The selectivity of the tuned component was flexible, such that suppression was stronger when the stimulus over the surround matched that over the receptive field. Our results therefore reveal strong interactions between spatial and temporal context in regulating the flow of signals through mouse SC, and suggest the presence of a subpopulation of neurons that might signal novelty in either space or time.
      Keywords: Sensory and Motor Systems
      PubDate: 2020-09-15T09:30:15-07:00
      DOI: 10.1523/ENEURO.0131-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Maternal Exposure to the Cannabinoid Agonist WIN 55,12,2 during Lactation
           Induces Lasting Behavioral and Synaptic Alterations in the Rat Adult
           Offspring of Both Sexes

    • Authors: Scheyer, A. F; Borsoi, M, Pelissier-Alicot, A.-L, Manzoni, O. J. J.
      Abstract: Consumption of cannabis during pregnancy and the lactation period is a rising public health concern (Scheyer et al., 2019). Exposure to synthetic or plant-derived cannabinoids via lactation disrupts the development of GABAergic neurons in the prefrontal cortex (PFC) and alters early-life behaviors (Scheyer et al., 2020b). Recently, additional data revealed that 9-tetrahydrocannabinol (THC) perinatal exposure via lactation causes lasting behavioral and neuronal consequences (Scheyer et al., 2020a). Here, the long-term effects in adult offspring of maternal exposure to the synthetic cannabinoid agonist WIN 55,12,2 are reported. The data demonstrate that rats exposed during lactation to WIN display social and motivational deficits at adulthood. These behavioral changes were paralleled by a specific loss of endocannabinoid-mediated long-term depression (eCB-LTD) in the PFC and nucleus accumbens (NAc), while other forms of synaptic plasticity remained intact. Thus, similarly to THC, perinatal WIN exposure via lactation induces behavioral and synaptic abnormalities lasting into adulthood.
      Keywords: Disorders of the Nervous System
      PubDate: 2020-09-15T09:30:15-07:00
      DOI: 10.1523/ENEURO.0144-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • An Electrophysiological Abstractness Effect for Metaphorical Meaning

    • Authors: Forgacs B.
      Abstract: Neuroimaging studies show that metaphors activate sensorimotor areas. These findings were interpreted as metaphors contributing to conceptual thought by mapping concrete, somatosensory information onto abstract ideas. But is sensorimotor information a necessary constituent of figurative meaning' The present study employed event-related potentials (ERPs) in a divided visual field paradigm with healthy adults to explore the role of sensorimotor feature processing in the comprehension of novel metaphors via the electrophysiological concreteness effect. Participants read French, novel adjective-noun expressions that were either metaphorical ("fat sentence") or literal ("fat hip"). While literal expressions evoked a typical concreteness effect, an enhanced frontal negativity during right hemisphere (RH) as opposed to left hemisphere (LH) presentation, metaphors showed no such sign of sensorimotor feature processing. Relative to literals, they evoked a sustained frontal negativity during LH presentation and similar amplitudes during RH presentation, but both of these effects were the greater the more abstract the metaphors were. It is the first time such an electrophysiological abstractness effect is reported, just the opposite of a concreteness effect. It is particularly noteworthy that ERPs evoked by metaphors were not contingent on figurativeness, novelty, meaningfulness, imageability, emotional valence, or arousal, only on abstractness. When compared with similarly novel literal expressions, metaphors did not evoke a typical N400 and did not activate the RH either. The findings shed new light on the neurocognitive machinery of figurative meaning construction, pervasive in everyday communication. Contrary to embodied cognition, the conceptual system might be organized around abstract representations and not sensorimotor information, even for lush, metaphorical language.
      Keywords: Integrative Systems
      PubDate: 2020-09-10T09:30:13-07:00
      DOI: 10.1523/ENEURO.0052-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Grp94 Regulates the Recruitment of Aneural AChR Clusters for the Assembly
           of Postsynaptic Specializations by Modulating ADF/Cofilin Activity and

    • Authors: Chan, Z. C.-K; Deng, L, Lee, C. W.
      Abstract: Temperature is a physiological factor that affects neuronal growth and synaptic homeostasis at the invertebrate neuromuscular junctions (NMJs); however, whether temperature stress could also regulate the structure and function of the vertebrate NMJs remains unclear. In this study, we use Xenopus laevis primary cultures as a vertebrate model system for investigating the involvement of heat shock protein 90 (HSP90) family of stress proteins in NMJ development. First, cold temperature treatment or HSP90 inhibition attenuates the formation of aneural acetylcholine receptor (AChR) clusters, but increases their stability after they are formed, in cultured muscles. HSP90 inhibition specifically affects the stability of aneural AChR clusters and their associated intracellular scaffolding protein rapsyn, instead of causing a global change in cell metabolism and protein expression in Xenopus muscle cultures. Upon synaptogenic stimulation, a specific HSP90 family member, glucose-regulated protein 94 (Grp94), modulates the phosphorylation and dynamic turnover of actin depolymerizing factor (ADF)/cofilin at aneural AChR clusters, leading to the recruitment of AChR molecules from aneural clusters to the assembly of agrin-induced postsynaptic specializations. Finally, postsynaptic Grp94 knock-down significantly inhibits nerve-induced AChR clustering and postsynaptic activity in nerve-muscle co-cultures as demonstrated by live-cell imaging and electrophysiological recording, respectively. Collectively, this study suggests that temperature-dependent alteration in Grp94 expression and activity inhibits the assembly of postsynaptic specializations through modulating ADF/cofilin phosphorylation and activity at aneural AChR clusters, which prevents AChR molecules from being recruited to the postsynaptic sites via actin-dependent vesicular trafficking, at developing vertebrate NMJs.
      Keywords: Development
      PubDate: 2020-09-08T09:30:13-07:00
      DOI: 10.1523/ENEURO.0025-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • In Vitro Testing of Voltage Indicators: Archon1, ArcLightD, ASAP1, ASAP2s,
           ASAP3b, Bongwoori-Pos6, BeRST1, FlicR1, and Chi-VSFP-Butterfly

    • Authors: Milosevic, M. M; Jang, J, McKimm, E. J, Zhu, M. H, Antic, S. D.
      Abstract: Genetically encoded voltage indicators (GEVIs) could potentially be used for mapping neural circuits at the plane of synaptic potentials and plateau potentials—two blind spots of GCaMP-based imaging. In the last year alone, several laboratories reported significant breakthroughs in the quality of GEVIs and the efficacy of the voltage imaging equipment. One major obstacle of using well performing GEVIs in the pursuit of interesting biological data is the process of transferring GEVIs between laboratories, as their reported qualities (e.g., membrane targeting, brightness, sensitivity, optical signal quality) are often difficult to reproduce outside of the laboratory of the GEVI origin. We have tested eight available GEVIs (Archon1, ArcLightD, ASAP1, ASAP2s, ASAP3b, Bongwoori-Pos6, FlicR1, and chi-VSFP-Butterfly) and two voltage-sensitive dyes (BeRST1 and di-4-ANEPPS). We used the same microscope, lens, and optical detector, while the light sources were interchanged. GEVI voltage imaging was attempted in the following three preparations: (1) cultured neurons, (2) HEK293 cells, and (3) mouse brain slices. Systematic measurements were successful only in HEK293 cells and brain slices. Despite the significant differences in brightness and dynamic response (ON rate), all tested indicators produced reasonable optical signals in brain slices and solid in vitro quality properties, in the range initially reported by the creator laboratories. Side-by-side comparisons between GEVIs and organic dyes obtained in HEK293 cells and brain slices by a "third party" (current data) will be useful for determining the right voltage indicator for a given research application.
      Keywords: Novel Tools and Methods
      PubDate: 2020-09-08T09:30:13-07:00
      DOI: 10.1523/ENEURO.0060-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Area 8A within the Posterior Middle Frontal Gyrus Underlies Cognitive
           Selection between Competing Visual Targets

    • Authors: Germann, J; Petrides, M.
      Abstract: There are several distinct areas in the granular part of the lateral frontal cortex, and these areas provide high-level regulation of cognitive processing. Lesions of the dorsolateral frontal cortex that include area 8A in the human brain and lesions restricted to area 8A in the macaque monkey have demonstrated impairments in tasks requiring selection between visual targets based on rules, such as conditional if/then rules. These same subjects show no impairment in the ability to discriminate between visual stimuli nor in the ability to learn selection rules in general. Area 8A can be considered as a key area for the top-down control of attentional selection. The present functional neuroimaging study demonstrates that activity in area 8A that lies on the posterior part of the middle frontal gyrus underlies the trial-to-trial selection between competing visual targets based on previously acquired conditional rules. Critically, the activity of area 8A could clearly be dissociated from activity related to the performance of eye movements per se that lies posterior to it. Thus, area 8A with its rich corticocortical connections with the posterior parietal region involved in spatial processing and the multisensory temporal cortex appears to be the key prefrontal area for the higher order selection between competing stimuli in the environment, most likely by the allocation of attention.
      Keywords: Cognition and Behavior
      PubDate: 2020-09-08T09:30:13-07:00
      DOI: 10.1523/ENEURO.0102-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Altered Expression of the m6A Methyltransferase METTL3 in Alzheimers

    • Authors: Huang, H; Camats-Perna, J, Medeiros, R, Anggono, V, Widagdo, J.
      Abstract: Cognitive impairment in Alzheimer’s disease (AD) is associated with dysregulation of the RNA and protein expression profiles in the brain. Recent studies have highlighted the importance of RNA post-transcriptional regulation (epitranscriptomics) in higher order brain functions. Specifically, N6-methyladenosine (m6A), which controls RNA stability, splicing, translation and trafficking, plays an important role in learning and memory. This raises the question of whether m6A signaling is perturbed in AD. To address this, we investigated the expression profile of known m6A-regulatory genes using a public RNA-seq dataset and identified a subset of genes which were significantly dysregulated in the human AD brain. Among these, genes encoding the m6A methyltransferase, METTL3, and a member of the m6A methyltransferase complex (MACOM), RBM15B, were downregulated and upregulated in the hippocampus, respectively. These findings were validated at the protein level using an independent cohort of postmortem human brain samples. Unexpectedly, we observed an accumulation of methyltransferase-like 3 (METTL3), but not RBM15B, in the insoluble fractions, which positively correlated with the levels of insoluble Tau protein in the postmortem human AD samples. Aberrant expression and distribution of METTL3 in the hippocampus of the AD brain may therefore represent an epitranscriptomic mechanism underlying the altered gene expression patterns associated with disease pathogenesis.
      Keywords: Disorders of the Nervous System
      PubDate: 2020-09-08T09:30:13-07:00
      DOI: 10.1523/ENEURO.0125-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • {theta}-{gamma} Cross-Frequency Transcranial Alternating Current
           Stimulation over the Trough Impairs Cognitive Control

    • Authors: Turi, Z; Mittner, M, Lehr, A, Bürger, H, Antal, A, Paulus, W.
      Abstract: Cognitive control is a mental process, which underlies adaptive goal-directed decisions. Previous studies have linked cognitive control to electrophysiological fluctuations in the band and - cross-frequency coupling (CFC) arising from the cingulate and frontal cortices. However, to date, the behavioral consequences of different forms of - CFC remain elusive. Here, we studied the behavioral effects of the - CFC via transcranial alternating current stimulation (tACS) designed to stimulate the frontal and cingulate cortices in humans. Using a double-blind, randomized, repeated measures study design, 24 healthy participants were subjected to three active and one control CFC-tACS conditions. In the active conditions, 80-Hz tACS was coupled to 4-Hz tACS. Specifically, in two of the active conditions, short bursts were coupled to the delivered cycle to coincide with either its peaks or troughs. In the third active condition, the phase of a cycle modulated the amplitude of the oscillation. In the fourth, control protocol, 80-Hz tACS was continuously superimposed over the 4-Hz tACS, therefore lacking any phase specificity in the CFC. During the 20 min of stimulation, the participants performed a Go/NoGo monetary reward-based and punishment-based instrumental learning task. A Bayesian hierarchical logistic regression analysis revealed that relative to the control, the peak-coupled tACS had no effects on the behavioral performance, whereas the trough-coupled tACS and, to a lesser extent, amplitude-modulated tACS reduced performance in conflicting trials. Our results suggest that cognitive control depends on the phase specificity of the - CFC.
      Keywords: Cognition and Behavior
      PubDate: 2020-09-08T09:30:13-07:00
      DOI: 10.1523/ENEURO.0126-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Local Design Principles at Hippocampal Synapses Revealed by an
           Energy-Information Trade-Off

    • Authors: Mahajan, G; Nadkarni, S.
      Abstract: Synapses across different brain regions display distinct structure-function relationships. We investigated the interplay of fundamental design constraints that shape the transmission properties of the excitatory CA3-CA1 pyramidal cell connection, a prototypic synapse for studying the mechanisms of learning in the mammalian hippocampus. This small synapse is characterized by probabilistic release of transmitter, which is markedly facilitated in response to naturally occurring trains of action potentials. Based on a physiologically motivated computational model of the rat CA3 presynaptic terminal, we show how unreliability and short-term dynamics of vesicular release work together to regulate the trade-off of information transfer versus energy use. We propose that individual CA3-CA1 synapses are designed to operate near the maximum possible capacity of information transmission in an efficient manner. Experimental measurements reveal a wide range of vesicular release probabilities at hippocampal synapses, which may be a necessary consequence of long-term plasticity and homeostatic mechanisms that manifest as presynaptic modifications of the release probability. We show that the timescales and magnitude of short-term plasticity (STP) render synaptic information transfer nearly independent of differences in release probability. Thus, individual synapses transmit optimally while maintaining a heterogeneous distribution of presynaptic strengths indicative of synaptically-encoded memory representations. Our results support the view that organizing principles that are evident on higher scales of neural organization percolate down to the design of an individual synapse.
      Keywords: Neuronal Excitability
      PubDate: 2020-09-08T09:30:13-07:00
      DOI: 10.1523/ENEURO.0521-19.2020
      Issue No: Vol. 7, No. 5 (2020)
  • OTX2 Non-Cell Autonomous Activity Regulates Inner Retinal Function

    • Authors: Torero Ibad, R; Mazhar, B, Vincent, C, Bernard, C, Degardin, J, Simonutti, M, Lamonerie, T, Di Nardo, A. A, Prochiantz, A, Moya, K. L.
      Abstract: OTX2 is a homeoprotein transcription factor expressed in photoreceptors and bipolar cells in the retina. OTX2, like many other homeoproteins, transfers between cells and exerts non-cell autonomous effects such as promoting the survival of retinal ganglion cells that do not express the protein. Here we used a genetic approach to target extracellular OTX2 in the retina by conditional expression of a secreted single-chain anti-OTX2 antibody. Compared with control mice, the expression of this antibody by parvalbumin-expressing neurons in the retina is followed by a reduction in visual acuity in 1-month-old mice with no alteration of the retinal structure or cell type number or aspect. The a-waves and b-waves measured by electroretinogram were also indistinguishable from those of control mice, suggesting no functional deficit of photoreceptors and bipolar cells. Mice expressing the OTX2-neutralizing antibody did show a significant doubling in the flicker amplitude and a reduction in oscillatory potential, consistent with a change in inner retinal function. Our results show that interfering in vivo with OTX2 non-cell autonomous activity in the postnatal retina leads to an alteration in inner retinal cell functions and causes a deficit in visual acuity.
      Keywords: Sensory and Motor Systems
      PubDate: 2020-09-04T09:31:02-07:00
      DOI: 10.1523/ENEURO.0012-19.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Endogenous Opsin 3 (OPN3) Protein Expression in the Adult Brain Using a
           Novel OPN3-mCherry Knock-In Mouse Model

    • Authors: Olinski, L. E; Tsuda, A. C, Kauer, J. A, Oancea, E.
      Abstract: The opsins have been studied extensively for their functions in visual phototransduction; however, the mechanisms underlying extraocular opsin signaling remain poorly understood. The first mammalian extraocular opsin to be discovered, opsin 3 (OPN3), was found in the brain more than two decades ago, yet its function remains unknown. A significant hindrance to studying OPN3 has been a lack of specific antibodies against mammalian OPN3, resulting in an incomplete understanding of its expression in the brain. Although Opn3 promoter-driven reporter mice have been generated to examine general OPN3 localization, they lack the regulated expression of the endogenous protein and the ability to study its subcellular localization. To circumvent these issues, we have created a knock-in OPN3-mCherry mouse model in which the fusion protein OPN3-mCherry is expressed under the endogenous Opn3 promoter. Viable and fertile homozygotes for the OPN3-mCherry allele were used to create an extensive map of OPN3-mCherry expression across the adult mouse brain. OPN3-mCherry was readily visualized in distinct layers of the cerebral cortex (CTX), the hippocampal formation (HCF), distinct nuclei of the thalamus, as well as many other regions in both neuronal and non-neuronal cells. Our mouse model offers a new platform to investigate the function of OPN3 in the brain.
      Keywords: Novel Tools and Methods
      PubDate: 2020-09-03T09:30:12-07:00
      DOI: 10.1523/ENEURO.0107-20.2020
      Issue No: Vol. 7, No. 5 (2020)
  • Traumatic Brain Injury Preserves Firing Rates But Disrupts Laminar
           Oscillatory Coupling and Neuronal Entrainment in Hippocampal CA1

    • Authors: Koch, P. F; Cottone, C, Adam, C. D, Ulyanova, A. V, Russo, R. J, Weber, M. T, Arena, J. D, Johnson, V. E, Wolf, J. A.
      Abstract: While hippocampal-dependent learning and memory are particularly vulnerable to traumatic brain injury (TBI), the functional status of individual hippocampal neurons and their interactions with oscillations are unknown following injury. Using the most common rodent TBI model and laminar recordings in CA1, we found a significant reduction in oscillatory input into the radiatum layer of CA1 after TBI. Surprisingly, CA1 neurons maintained normal firing rates despite attenuated input, but did not maintain appropriate synchronization with this oscillatory input or with local high-frequency oscillations. Normal synchronization between these coordinating oscillations was also impaired. Simultaneous recordings of medial septal neurons known to participate in theta oscillations revealed increased GABAergic/glutamatergic firing rates postinjury under anesthesia, potentially because of a loss of modulating feedback from the hippocampus. These results suggest that TBI leads to a profound disruption of connectivity and oscillatory interactions, potentially disrupting the timing of CA1 neuronal ensembles that underlie aspects of learning and memory.
      Keywords: Disorders of the Nervous System
      PubDate: 2020-09-02T09:36:00-07:00
      DOI: 10.1523/ENEURO.0495-19.2020
      Issue No: Vol. 7, No. 5 (2020)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
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