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Jurnal Vektor Penyakit
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ISSN (Print) 1978-3647 - ISSN (Online) 2354-8835
Published by Badan Penelitian dan Pengembangan Kesehatan Homepage  [6 journals]
  • Lack of Causal Roles of Cannabinoid and Dopamine Neurotransmitter Systems
           in Orbitofrontal and Piriform Cortex in Fentanyl Relapse in Rats

    • Authors: Claypool, S. M; Behdin, S, Applebey, S. V, Orihuel, J, Ma, Z, Reiner, D. J.
      Abstract: AbstractThe orbitofrontal cortex (OFC) and piriform cortex (Pir) play a role in fentanyl relapse after food choice-induced voluntary abstinence, a procedure mimicking abstinence because of availability of alternative nondrug rewards. We used in situ hybridization and pharmacology to determine the role of OFC and Pir cannabinoid and dopamine receptors in fentanyl relapse. We trained male and female rats to self-administer food pellets for 6 d (6 h/d) and intravenous fentanyl (2.5 µg/kg/infusion) for 12 d (6 h/d). We assessed fentanyl relapse after 12 discrete choice sessions between fentanyl and food (20 trials/d), in which rats voluntarily reduced fentanyl self-administration. We used RNAscope to determine whether fentanyl relapse is associated with activity (indicated by Fos) in OFC and Pir cells expressing Cnr1 [which encodes cannabinoid 1 (CB1) receptors] or Drd1 and Drd2 (which encode dopamine D1 and D2 receptors). We injected a CB1 receptor antagonist or agonist (0.3 or 1.0 µg AM251 or WIN55,212-2/hemisphere) into OFC or a dopamine D1 receptor antagonist (1.0 or 3.0 µg SCH39166/hemisphere) into Pir to determine the effect on fentanyl relapse. Fentanyl relapse was associated with OFC cells co-expressing Fos and Cnr1 and Pir cells co-expressing Fos and Drd1. However, injections of the CB1 receptor antagonist AM251 or agonist WIN55,212-2 into OFC or the dopamine D1 receptor antagonist SCH39166 into Pir had no effect on fentanyl relapse. Fentanyl relapse is associated with activation of Cnr1-expressing OFC cells and Drd1-expressing Pir cells, but pharmacological manipulations do not support causal roles of OFC CB1 receptors or Pir dopamine D1 receptors in fentanyl relapse.
      Keywords: Cognition and Behavior
      PubDate: 2022-07-20T09:30:18-07:00
      DOI: 10.1523/ENEURO.0496-21.2022
      Issue No: Vol. 9, No. 4 (2022)
       
  • PLC{beta}-Mediated Depletion of PIP2 and ATP-Sensitive K+ Channels Are
           Involved in Arginine Vasopressin-Induced Facilitation of Neuronal
           Excitability and LTP in the Dentate Gyrus

    • Authors: Lei, S; Boyle, C. A, Mastrud, M.
      Abstract: AbstractArginine vasopressin (AVP) serves as a neuromodulator in the brain. The hippocampus is one of the major targets for AVP, as it has been demonstrated that the hippocampus receives vasopressinergic innervation and expresses AVP receptors. The dentate gyrus (DG) granule cells (GCs) serve as a gate governing the inflow of information to the hippocampus. High densities of AVP receptors are expressed in the DG GCs. However, the roles and the underlying cellular and molecular mechanisms of AVP in the DG GCs have not been determined. We addressed this question by recording from the DG GCs in rat hippocampal slices. Our results showed that application of AVP concentration-dependently evoked an inward holding current recorded from the DG GCs. AVP depolarized the DG GCs and increased their action potential firing frequency. The excitatory effects of AVP were mediated by activation of V1a receptors and required the function of phospholipase Cβ (PLCβ). Whereas intracellular Ca2+ release and protein kinase C activity were unnecessary, PLCβ-induced depletion of phosphatidylinositol 4,5-bisphosphate was involved in AVP-evoked excitation of the DG GCs. AVP excited the DG GCs by depression of the ATP-sensitive K+ channels, which were required for AVP-elicited facilitation of long-term potentiation at the perforant path–GC synapses. Our results may provide a cellular and molecular mechanism to explain the physiological functions of AVP, such as learning and memory, and pathologic disorders like anxiety.
      Keywords: Neuronal Excitability
      PubDate: 2022-07-19T09:30:18-07:00
      DOI: 10.1523/ENEURO.0120-22.2022
      Issue No: Vol. 9, No. 4 (2022)
       
  • Enhancement of Motor Cortical Gamma Oscillations and Sniffing Activity by
           Medial Forebrain Bundle Stimulation Precedes Locomotion

    • Authors: Yoshimoto, A; Shibata, Y, Kudara, M, Ikegaya, Y, Matsumoto, N.
      Abstract: The medial forebrain bundle (MFB) is a white matter pathway that traverses through mesolimbic structures and includes dopaminergic neural fibers ascending from the ventral tegmental area (VTA). Since dopaminergic signals represent hedonic responses, electrical stimulation of the MFB in animals has been used as a neural reward for operant and spatial tasks. MFB stimulation strongly motivates animals to rapidly learn to perform a variety of behavioral tasks to obtain a reward. Although the MFB is known to connect various brain regions and MFB stimulation dynamically modulates animal behavior, how central and peripheral functions are affected by MFB stimulation per se is poorly understood. To address this question, we simultaneously recorded electrocorticograms (ECoGs) in the primary motor cortex (M1), primary somatosensory cortex (S1), and olfactory bulb (OB) of behaving rats while electrically stimulating the MFB. We found that MFB stimulation increased the locomotor activity of rats. Spectral analysis confirmed that immediately after MFB stimulation, sniffing activity was facilitated and the power of gamma oscillations in the M1 was increased. After sniffing activity and motor cortical gamma oscillations were facilitated, animals started to move. These results provide insight into the importance of sniffing activity and cortical gamma oscillations for motor execution and learning facilitated by MFB stimulation.
      Keywords: Cognition and Behavior
      PubDate: 2022-07-19T09:30:18-07:00
      DOI: 10.1523/ENEURO.0521-21.2022
      Issue No: Vol. 9, No. 4 (2022)
       
  • Ultrasensitive Quantification of Multiple Estrogens in Songbird Blood and
           Microdissected Brain by LC-MS/MS

    • Authors: Jalabert, C; Shock, M. A, Ma, C, Bootsma, T. J, Liu, M. Q, Soma, K. K.
      Abstract: AbstractNeuroestrogens are synthesized within the brain and regulate social behavior, learning and memory, and cognition. In song sparrows, Melospiza melodia, 17β-estradiol (17β-E2) promotes aggressive behavior, including during the nonbreeding season when circulating steroid levels are low. Estrogens are challenging to measure because they are present at very low levels, and current techniques often lack the sensitivity required. Furthermore, current methods often focus on 17β-E2 and disregard other estrogens. Here, we developed and validated a method to measure four estrogens [estrone (E1), 17β-E2, 17α-estradiol (17α-E2), estriol (E3)] simultaneously in microdissected songbird brain, with high specificity, sensitivity, accuracy, and precision. We used liquid chromatography tandem mass spectrometry (LC-MS/MS), and to improve sensitivity, we derivatized estrogens using 1,2-dimethylimidazole-5-sulfonyl-chloride (DMIS). The straightforward protocol improved sensitivity by 10-fold for some analytes. There is substantial regional variation in neuroestrogen levels in brain areas that regulate social behavior in male song sparrows. For example, the auditory area NCM, which has high aromatase levels, has the highest E1 and 17β-E2 levels. In contrast, estrogen levels in blood are very low. Estrogen levels in both brain and circulation are lower in the nonbreeding season than in the breeding season. This technique will be useful for estrogen measurement in songbirds and potentially other animal models.
      Keywords: Cognition and Behavior
      PubDate: 2022-07-15T09:30:17-07:00
      DOI: 10.1523/ENEURO.0037-22.2022
      Issue No: Vol. 9, No. 4 (2022)
       
  • Differential Effects of the G-Protein-Coupled Estrogen Receptor (GPER) on
           Rat Embryonic (E18) Hippocampal and Cortical Neurons

    • Authors: Pemberton, K; Rosato, M, Dedert, C, DeLeon, C, Arnatt, C, Xu, F.
      Abstract: AbstractEstrogen plays fundamental roles in nervous system development and function. Traditional studies examining the effect of estrogen in the brain have focused on the nuclear estrogen receptors (ERs), ERα and ERβ. Studies related to the extranuclear, membrane-bound G-protein-coupled ER (GPER/GPR30) have revealed a neuroprotective role for GPER in mature neurons. In this study, we investigated the differential effects of GPER activation in primary rat embryonic day 18 (E18) hippocampal and cortical neurons. Microscopy imaging, multielectrode array (MEA), and Ca2+ imaging experiments revealed that GPER activation with selective agonist, G-1, and nonselective agonist, 17β-estradiol (E2), increased neural growth, neural firing activity, and intracellular Ca2+ more profoundly in hippocampal neurons than in cortical neurons. The GPER-mediated Ca2+ rise in hippocampal neurons involves internal Ca2+ store release via activation of phospholipase C (PLC) and extracellular entry via Ca2+ channels. Immunocytochemistry results revealed no observable difference in GPER expression/localization in neurons, yet real-time qPCR (RT-qPCR) and Western blotting showed a higher GPER expression in the cortex than hippocampus, implying that GPER expression level may not fully account for its robust physiological effects in hippocampal neurons. We used RNA sequencing data to identify distinctly enriched pathways and significantly expressed genes in response to G-1 or E2 in cultured rat E18 hippocampal and cortical neurons. In summary, the identification of differential effects of GPER activation on hippocampal and cortical neurons in the brain and the determination of key genes and molecular pathways are instrumental toward an understanding of estrogen’s action in early neuronal development.
      Keywords: Development
      PubDate: 2022-07-15T09:30:17-07:00
      DOI: 10.1523/ENEURO.0475-21.2022
      Issue No: Vol. 9, No. 4 (2022)
       
  • Navigating the Statistical Minefield of Model Selection and Clustering in
           Neuroscience

    • Authors: Kiraly, B; Hangya, B.
      Abstract: AbstractModel selection is often implicit: when performing an ANOVA, one assumes that the normal distribution is a good model of the data; fitting a tuning curve implies that an additive and a multiplicative scaler describes the behavior of the neuron; even calculating an average implicitly assumes that the data were sampled from a distribution that has a finite first statistical moment: the mean. Model selection may be explicit, when the aim is to test whether one model provides a better description of the data than a competing one. As a special case, clustering algorithms identify groups with similar properties within the data. They are widely used from spike sorting to cell type identification to gene expression analysis. We discuss model selection and clustering techniques from a statistician’s point of view, revealing the assumptions behind, and the logic that governs the various approaches. We also showcase important neuroscience applications and provide suggestions how neuroscientists could put model selection algorithms to best use as well as what mistakes should be avoided.
      Keywords: Reviews, Novel Tools and Methods
      PubDate: 2022-07-14T10:16:23-07:00
      DOI: 10.1523/ENEURO.0066-22.2022
      Issue No: Vol. 9, No. 4 (2022)
       
  • Learning Spatiotemporal Properties of Hippocampal Place Cells

    • Authors: Lian, Y; Burkitt, A. N.
      Abstract: It is well known that hippocampal place cells have spatiotemporal properties, namely, that they generally respond to a single spatial location of a small environment, and they also display the temporal response property of theta phase precession, namely, that the phase of spiking relative to the theta wave shifts from the late phase to early phase as the animal crosses the place field. Grid cells in Layer II of the medial entorhinal cortex (MEC) also have spatiotemporal properties similar to hippocampal place cells, except that grid cells respond to multiple spatial locations that form a hexagonal pattern. Because the EC is the upstream area that projects strongly to the hippocampus, a number of EC-hippocampus learning models have been proposed to explain how the spatial receptive field properties of place cells emerge via synaptic plasticity. However, the question of how the phase precession properties of place cells and grid cells are related has remained unclear. This study shows how theta phase precession in hippocampal place cells can emerge from MEC input as a result of synaptic plasticity, demonstrating that a learning model based on non-negative sparse coding can account for both the spatial and temporal properties of hippocampal place cells. Although both MEC grid cells and other EC spatial cells contribute to the spatial properties of hippocampal place cells, it is the MEC grid cells that predominantly determine the temporal response properties of hippocampal place cells displayed here.
      Keywords: Integrative Systems
      PubDate: 2022-07-12T09:30:14-07:00
      DOI: 10.1523/ENEURO.0519-21.2022
      Issue No: Vol. 9, No. 4 (2022)
       
  • A Behavioral Receptive Field for Ocular Following in Monkeys: Spatial
           Summation and Its Spatial Frequency Tuning

    • Authors: Barthelemy, F. V; Fleuriet, J, Perrinet, L. U, Masson, G. S.
      Abstract: In human and nonhuman primates, reflexive tracking eye movements can be initiated at very short latency in response to a rapid shift of the image. Previous studies in humans have shown that only a part of the central visual field is optimal for driving ocular following responses. Herein, we have investigated spatial summation of motion information, across a wide range of spatial frequencies and speeds of drifting gratings by recording short-latency ocular following responses in macaque monkeys. We show that the optimal stimulus size for driving ocular responses cover a small (diameter,
      Keywords: Sensory and Motor Systems
      PubDate: 2022-07-11T09:30:14-07:00
      DOI: 10.1523/ENEURO.0374-21.2022
      Issue No: Vol. 9, No. 4 (2022)
       
  • Sex Differences in the Alcohol-Mediated Modulation of BLA Network States

    • Authors: DiLeo, A; Antonoudiou, P, Ha, S, Maguire, J. L.
      Abstract: AbstractAlcohol use, reported by 85% of adults in the United States, is highly comorbid with mood disorders, like generalized anxiety disorder and major depression. The basolateral amygdala (BLA) is an area of the brain that is heavily implicated in both mood disorders and alcohol use disorder. Importantly, the modulation of BLA network/oscillatory states via parvalbumin (PV)-positive GABAergic interneurons has been shown to control the behavioral expression of fear and anxiety. Further, PV interneurons express a high density of subunit-containing GABAA receptors (GABAARs), which are sensitive to low concentrations of alcohol. Therefore, we hypothesized that the effects of alcohol may modulate BLA network states that have been associated with fear and anxiety behaviors via -GABAARs on PV interneurons in the BLA. Given the impact of ovarian hormones on the expression of -GABAARs, we also examined the ability of alcohol to modulate local field potentials in the BLA from male and female C57BL/6J and Gabrd–/– mice after acute and repeated exposure to alcohol. Here, we demonstrate that acute and repeated alcohol can differentially modulate oscillatory states in male and female C57BL/6J mice, a process that involves -GABAARs. This is the first study to demonstrate that alcohol is capable of altering network states implicated in both anxiety and alcohol use disorders.
      Keywords: Neuronal Excitability
      PubDate: 2022-07-08T09:30:12-07:00
      DOI: 10.1523/ENEURO.0010-22.2022
      Issue No: Vol. 9, No. 4 (2022)
       
  • Robust, Long-Term Video EEG Monitoring in a Porcine Model of
           Post-Traumatic Epilepsy

    • Authors: Martinez-Ramirez, L; Slate, A, Price, G. D, Duhaime, A.-C, Staley, K. J, Costine-Bartell, B. A.
      Abstract: AbstractTo date, post-traumatic epilepsy (PTE) research in large-animal models has been limited. Recent advances in neocortical microscopy have made possible new insights into neocortical PTE. However, it is very difficult to engender convincing neocortical PTE in rodents. Thus, large-animal models that develop neocortical PTE may provide useful insights that also can be more comparable to human patients. Because gyrencephalic species have prolonged latent periods, long-term video EEG recording is required. Here, we report a fully subcutaneous EEG implant with synchronized video in freely ambulatory swine for up to 13 months during epileptogenesis following bilateral cortical impact injuries or sham surgery The advantages of this system include the availability of a commercially available system that is simple to install, a low failure rate after surgery for EEG implantation, radiotelemetry that enables continuous monitoring of freely ambulating animals, excellent synchronization to video to EEG, and a robust signal-to-noise ratio. The disadvantages of this system in this species and age are the accretion of skull bone, which entirely embedded a subset of skull screws and EEG electrodes, and the inability to rearrange the EEG electrode array. These disadvantages may be overcome by splicing a subdural electrode strip to the electrode leads so that skull growth is less likely to interfere with long-term signal capture and by placing two implants for a more extensive montage. This commercially available system in this bilateral cortical impact swine model may be useful to a wide range of investigators studying epileptogenesis in PTE.
      Keywords: Disorders of the Nervous System
      PubDate: 2022-07-08T09:30:12-07:00
      DOI: 10.1523/ENEURO.0025-22.2022
      Issue No: Vol. 9, No. 4 (2022)
       
  • Efferent Activity Controls Hair Cell Response to Mechanical
           Overstimulation

    • Authors: Lin, C.-H. J; Bozovic, D.
      Abstract: AbstractThe efferent pathway strengthens the auditory system for optimal performance by fine-tuning the response and protecting the inner ear from noise-induced damage. Although it has been well documented that efference helps defend against hair cell and synaptic extinction, the mechanisms of its otoprotective role have still not been established. Specifically, the effect of efference on an individual hair cell’s recovery from mechanical overstimulation has not been demonstrated. In the current work, we explored the impact of efferent stimulation on this recovery using in vitro preparations of hair cells situated in the sacculi of American bullfrogs (Rana catesbeiana). In the absence of efferent stimulus, exposure of a hair bundle to high-amplitude mechanical deflection detuned it from its oscillatory regime, with the extent of detuning dependent on the applied signal. Efferent actuation concomitant with the hair bundle’s relaxation from a high-amplitude deflection notably changed the recovery profile and often entirely eliminated the transition to quiescence. Our findings indicate that the efferent system acts as a control mechanism that determines the dynamic regime in which the hair cell is poised.
      Keywords: Sensory and Motor Systems
      PubDate: 2022-07-08T09:30:12-07:00
      DOI: 10.1523/ENEURO.0198-22.2022
      Issue No: Vol. 9, No. 4 (2022)
       
  • A Subregion of Insular Cortex Is Required for Rapid Taste-Visceral
           Integration and Consequent Conditioned Taste Aversion and Avoidance
           Expression in Rats

    • Authors: Jung, A.-H; King, C. T, Blonde, G. D, King, M, Griggs, C, Hashimoto, K, Spector, A. C, Schier, L. A.
      Abstract: AbstractPostingestive signals are important for shaping appetitive and consummatory responses, but the brain mechanisms required to assimilate interoceptive events with those at the frontlines of ingestion (taste-guided) are poorly understood. Here, we investigated whether an insular cortex (IC) region, which receives viscerosensory input, including gustatory, is required to modify taste-elicited consummatory reactions in response to a real-time interoceptive change using a serial taste reactivity (TR) test where the rats’ oromotor and somatic reactions to intraoral (IO) infusions of sucrose were periodically assessed over 45 min following lithium chloride (LiCl) administration. Results showed that neurally-intact rats shifted from an ingestive repertoire to an aversive one as LiCl took effect. Overall, this hedonic shift was delayed in rats with bilateral neurotoxic IC lesions. Rats with greater neuronal loss in posterior gustatory IC displayed fewer aversive reactions to sucrose following this initial LiCl injection. We further assessed whether the failure to integrate interoceptive feedback with ongoing taste-guided behavior impaired acquisition and/or expression of conditioned aversion and/or avoidance in these same rats. Although, as a group, LiCl-injected rats with IC lesions subsequently avoided the sugar in a 48-h two-bottle test, their preference for sucrose was significantly greater than that of the LiCl-injected neurally-intact rats. Overall lesion size, as well as proportion of the posterior gustatory and/or anterior visceral IC were each associated with impaired avoidance. These findings reveal new roles for the posterior gustatory and anterior visceral ICs in multisensory integrative function.
      Keywords: Integrative Systems
      PubDate: 2022-07-07T09:30:10-07:00
      DOI: 10.1523/ENEURO.0527-21.2022
      Issue No: Vol. 9, No. 4 (2022)
       
  • Neuronal Correlates of Hyperalgesia and Somatic Signs of Heroin Withdrawal
           in Male and Female Mice

    • Authors: Alvarez-Bagnarol, Y; Marchette, R. C. N, Francis, C, Morales, M, Vendruscolo, L. F.
      Abstract: AbstractOpioid withdrawal involves the manifestation of motivational and somatic symptoms. However, the brain structures that are involved in the expression of different opioid withdrawal signs remain unclear. We induced opioid dependence by repeatedly injecting escalating heroin doses in male and female C57BL/6J mice. We assessed hyperalgesia during spontaneous heroin withdrawal and somatic signs of withdrawal that was precipitated by the preferential μ-opioid receptor antagonist naloxone. Heroin-treated mice exhibited significantly higher hyperalgesia and somatic signs than saline-treated mice. Following behavioral assessment, we measured regional changes in brain activity by automated the counting of c-Fos expression (a marker of cellular activity). Using Principal Component Analysis, we determined the association between behavior (hyperalgesia and somatic signs of withdrawal) and c-Fos expression in different brain regions. Hyperalgesia was associated with c-Fos expression in the lateral hypothalamus, central nucleus of the amygdala, ventral tegmental area, parabrachial nucleus, dorsal raphe (DR), and locus coeruleus (LC). Somatic withdrawal was associated with c-Fos expression in the paraventricular nucleus of the thalamus, lateral habenula, DR, and LC. Thus, hyperalgesia and somatic withdrawal signs were each associated with c-Fos expression in unique sets of brain areas. The expression of c-Fos in the DR and LC was associated with both hyperalgesia and somatic withdrawal. Understanding common neurobiological mechanisms of acute and protracted opioid withdrawal may help identify new targets for treating this salient aspect of opioid use disorder.
      Keywords: Disorders of the Nervous System
      PubDate: 2022-07-06T09:30:29-07:00
      DOI: 10.1523/ENEURO.0106-22.2022
      Issue No: Vol. 9, No. 4 (2022)
       
 
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