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https://www.readbyqxmd.com/read/27911814/distinct-cortical-and-striatal-actions-of-a-%C3%AE-arrestin-biased-dopamine-d2-receptor-ligand-reveal-unique-antipsychotic-like-properties
#1
Nikhil M Urs, Steven M Gee, Thomas F Pack, John D McCorvy, Tama Evron, Joshua C Snyder, Xiaobao Yang, Ramona M Rodriguiz, Emiliana Borrelli, William C Wetsel, Jian Jin, Bryan L Roth, Patricio O'Donnell, Marc G Caron
The current dopamine (DA) hypothesis of schizophrenia postulates striatal hyperdopaminergia and cortical hypodopaminergia. Although partial agonists at DA D2 receptors (D2Rs), like aripiprazole, were developed to simultaneously target both phenomena, they do not effectively improve cortical dysfunction. In this study, we investigate the potential for newly developed β-arrestin2 (βarr2)-biased D2R partial agonists to simultaneously target hyper- and hypodopaminergia. Using neuron-specific βarr2-KO mice, we show that the antipsychotic-like effects of a βarr2-biased D2R ligand are driven through both striatal antagonism and cortical agonism of D2R-βarr2 signaling...
December 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27895555/spike-timing-rigidity-is-maintained-in-bursting-neurons-under-pentobarbital-induced-anesthetic-conditions
#2
Risako Kato, Masanori Yamanaka, Eiko Yokota, Noriaki Koshikawa, Masayuki Kobayashi
Pentobarbital potentiates γ-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission by prolonging the open time of GABAA receptors. However, it is unknown how pentobarbital regulates cortical neuronal activities via local circuits in vivo. To examine this question, we performed extracellular unit recording in rat insular cortex under awake and anesthetic conditions. Not a few studies apply time-rescaling theorem to detect the features of repetitive spike firing. Similar to these methods, we define an average spike interval locally in time using random matrix theory (RMT), which enables us to compare different activity states on a universal scale...
2016: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/27828957/plasticity-in-single-axon-glutamatergic-connection-to-gabaergic-interneurons-regulates-complex-events-in-the-human-neocortex
#3
Viktor Szegedi, Melinda Paizs, Eszter Csakvari, Gabor Molnar, Pal Barzo, Gabor Tamas, Karri Lamsa
In the human neocortex, single excitatory pyramidal cells can elicit very large glutamatergic EPSPs (VLEs) in inhibitory GABAergic interneurons capable of triggering their firing with short (3-5 ms) delay. Similar strong excitatory connections between two individual neurons have not been found in nonhuman cortices, suggesting that these synapses are specific to human interneurons. The VLEs are crucial for generating neocortical complex events, observed as single pyramidal cell spike-evoked discharge of cell assemblies in the frontal and temporal cortices...
November 2016: PLoS Biology
https://www.readbyqxmd.com/read/27807408/cortical-neural-computation-by-discrete-results-hypothesis
#4
REVIEW
Carlos Castejon, Angel Nuñez
One of the most challenging problems we face in neuroscience is to understand how the cortex performs computations. There is increasing evidence that the power of the cortical processing is produced by populations of neurons forming dynamic neuronal ensembles. Theoretical proposals and multineuronal experimental studies have revealed that ensembles of neurons can form emergent functional units. However, how these ensembles are implicated in cortical computations is still a mystery. Although cell ensembles have been associated with brain rhythms, the functional interaction remains largely unclear...
2016: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/27806991/hippocampal-perineuronal-nets-are-required-for-the-sustained-antidepressant-effect-of-ketamine
#5
Jennifer J Donegan, Daniel J Lodge
BACKGROUND: NMDA receptor antagonists, like ketamine, produce a rapid-acting and long-lasting antidepressant effect. Although the mechanism is not completely understood, ketamine is thought to preferentially target NMDA receptors on fast-spiking parvalbumin (PV)-containing interneurons. The function of PV-containing interneurons is dependent on perineuronal nets, a specialized form of extracellular matrix that surrounds these cells. METHODS: Chondroitinase was used to enzymatically degrade perineuronal nets surrounding PV-containing interneurons in the ventral hippocampus (vHipp), a region that is involved in the antidepressant response to ketamine...
November 2, 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27803650/firing-frequency-maxima-of-fast-spiking-neurons-in-human-monkey-and-mouse-neocortex
#6
Bo Wang, Wei Ke, Jing Guang, Guang Chen, Luping Yin, Suixin Deng, Quansheng He, Yaping Liu, Ting He, Rui Zheng, Yanbo Jiang, Xiaoxue Zhang, Tianfu Li, Guoming Luan, Haidong D Lu, Mingsha Zhang, Xiaohui Zhang, Yousheng Shu
Cortical fast-spiking (FS) neurons generate high-frequency action potentials (APs) without apparent frequency accommodation, thus providing fast and precise inhibition. However, the maximal firing frequency that they can reach, particularly in primate neocortex, remains unclear. Here, by recording in human, monkey, and mouse neocortical slices, we revealed that FS neurons in human association cortices (mostly temporal) could generate APs at a maximal mean frequency (Fmean) of 338 Hz and a maximal instantaneous frequency (Finst) of 453 Hz, and they increase with age...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27793780/%C3%AE-4%C3%AE-2-%C3%A2-nicotinic-receptors-stimulate-gaba-release-onto-fast-spiking-cells-in-layer-v-of-mouse-prefrontal-fr2-cortex
#7
Patrizia Aracri, Simone Meneghini, Aurora Coatti, Alida Amadeo, Andrea Becchetti
Nicotinic acetylcholine receptors (nAChRs) produce widespread and complex effects on neocortex excitability. We studied how heteromeric nAChRs regulate inhibitory post-synaptic currents (IPSCs), in fast-spiking (FS) layer V neurons of the mouse frontal area 2 (Fr2). In the presence of blockers of ionotropic glutamate receptors, tonic application of 10μM nicotine augmented the spontaneous IPSC frequency, with minor alterations of amplitudes and kinetics. These effects were studied since the 3rd postnatal week, and persisted throughout the first two months of postnatal life...
October 26, 2016: Neuroscience
https://www.readbyqxmd.com/read/27783219/long-term-plasticity-in-identified-hippocampal-gabaergic-interneurons-in-the-ca1-area-in-vivo
#8
Petrina Yau-Pok Lau, Linda Katona, Peter Saghy, Kathryn Newton, Peter Somogyi, Karri P Lamsa
Long-term plasticity is well documented in synapses between glutamatergic principal cells in the cortex both in vitro and in vivo. Long-term potentiation (LTP) and -depression (LTD) have also been reported in glutamatergic connections to hippocampal GABAergic interneurons expressing parvalbumin (PV+) or nitric oxide synthase (NOS+) in brain slices, but plasticity in these cells has not been tested in vivo. We investigated synaptically-evoked suprathreshold excitation of identified hippocampal neurons in the CA1 area of urethane-anaesthetized rats...
October 25, 2016: Brain Structure & Function
https://www.readbyqxmd.com/read/27780732/altered-postnatal-maturation-of-striatal-gabaergic-interneurons-in-a-phenotypic-animal-model-of-dystonia
#9
Christoph Bode, Franziska Richter, Christine Spröte, Tanja Brigadski, Anne Bauer, Simone Fietz, Jean-Marc Fritschy, Angelika Richter
GABAergic disinhibition has been suggested to play a critical role in the pathophysiology of several basal ganglia disorders, including dystonia, a common movement disorder. Previous studies have shown a deficit of striatal GABAergic interneurons (IN) in the dt(sz) mutant hamster, one of the few phenotypic animal models of dystonia. However, mechanisms underlying this deficit are largely unknown. In the present study, we investigated the migration and maturation of striatal IN during postnatal development (18days of age) and at age of highest severity of dystonia (33days of age) in this hamster model...
January 2017: Experimental Neurology
https://www.readbyqxmd.com/read/27749825/layer-4-fast-spiking-interneurons-filter-thalamocortical-signals-during-active-somatosensation
#10
Jianing Yu, Diego A Gutnisky, S Andrew Hires, Karel Svoboda
We rely on movement to explore the environment, for example, by palpating an object. In somatosensory cortex, activity related to movement of digits or whiskers is suppressed, which could facilitate detection of touch. Movement-related suppression is generally assumed to involve corollary discharges. Here we uncovered a thalamocortical mechanism in which cortical fast-spiking interneurons, driven by sensory input, suppress movement-related activity in layer 4 (L4) excitatory neurons. In mice locating objects with their whiskers, neurons in the ventral posteromedial nucleus (VPM) fired in response to touch and whisker movement...
October 17, 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27746347/propofol-induced-spike-firing-suppression-is-more-pronounced-in-pyramidal-neurons-than-in-fast-spiking-neurons-in-the-rat-insular-cortex
#11
Keisuke Kaneko, Yuko Koyanagi, Yoshiyuki Oi, Masayuki Kobayashi
Propofol is a major intravenous anesthetic that facilitates GABAA receptor-mediated inhibitory synaptic currents and modulates inward current (Ih), K(+), and voltage-gated Na(+) currents. This propofol-induced modulation of ionic currents changes intrinsic membrane properties and repetitive spike firing in cortical pyramidal neurons. However, it has been unknown whether propofol modulates these electrophysiological properties in GABAergic neurons, which express these ion channels at different levels. This study examined whether pyramidal and GABAergic neuronal properties are differentially modulated by propofol in the rat insular cortical slice preparation...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27746131/identified-cellular-correlates-of-neocortical-ripple-and-high-gamma-oscillations-during-spindles-of-natural-sleep
#12
Robert G Averkin, Viktor Szemenyei, Sándor Bordé, Gábor Tamás
Ultra-high-frequency network events in the hippocampus are instrumental in a dialogue with the neocortex during memory formation, but the existence of transient ∼200 Hz network events in the neocortex is not clear. Our recordings from neocortical layer II/III of freely behaving rats revealed field potential events at ripple and high-gamma frequencies repeatedly occurring at troughs of spindle oscillations during sleep. Juxtacellular recordings identified subpopulations of fast-spiking, parvalbumin-containing basket cells with epochs of firing at ripple (∼200 Hz) and high-gamma (∼120 Hz) frequencies detected during spindles and centered with millisecond precision at the trough of spindle waves in phase with field potential events but phase shifted relative to pyramidal cell firing...
November 23, 2016: Neuron
https://www.readbyqxmd.com/read/27733597/changes-in-activity-of-fast-spiking-interneurons-of-the-monkey-striatum-during-reaching-at-a-visual-target
#13
Kévin Marche, Paul Apicella
Recent works highlight the importance of local inhibitory interneurons in regulating the function of the striatum. In particular, fast-spiking interneurons (FSIs), which likely correspond to a subgroup of GABAergic interneurons, have been involved in the control of movement by exerting strong inhibition on striatal output pathways. However, little is known about the exact contribution of these presumed interneurons in movement preparation, initiation, and execution. We recorded the activity of FSIs in the striatum of monkeys as they performed reaching movements to a visual target under two task conditions: one in which the movement target was presented at unsignaled left or right locations, and another in which advance information about target location was available, thus allowing monkeys to react faster...
October 12, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27725218/opioid-subtype-and-cell-type-dependent-regulation-of-inhibitory-synaptic-transmission-in-the-rat-insular-cortex
#14
Eiko Yokota, Yuko Koyanagi, Kiyofumi Yamamoto, Yoshiyuki Oi, Noriaki Koshikawa, Masayuki Kobayashi
The insular cortex (IC) plays a principal role in the regulation of pain processing. Although opioidergic agonists depress cortical excitatory synaptic transmission, little is known about opioidergic roles in inhibitory synaptic transmission. In the IC, the opioid receptors differentially regulate the excitatory propagation: agonists of the mu (MOR), delta (DOR), and kappa (KOR) exhibit suppressive, facilitative, and little effects, respectively. Thus, we aimed to examine the effects of opioid receptor agonists on unitary inhibitory postsynaptic currents (uIPSCs) in the IC...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27710792/principles-of-synaptic-organization-of-gabaergic-interneurons-in-the-striatum
#15
Christoph Straub, Jessica Lizette Saulnier, Aurelien Bègue, Danielle D Feng, Kee Wui Huang, Bernardo Luis Sabatini
The striatum, the entry nucleus of the basal ganglia, lacks laminar or columnar organization of its principal cells; nevertheless, functional data suggest that it is spatially organized. Here we examine whether the connectivity and synaptic organization of striatal GABAergic interneurons contributes to such spatial organization. Focusing on the two main classes of striatal GABAergic interneurons (fast-spiking interneurons [FSIs] and low-threshold-spiking interneurons [LTSIs]), we apply a combination of optogenetics and viral tracing approaches to dissect striatal microcircuits in mice...
October 5, 2016: Neuron
https://www.readbyqxmd.com/read/27707966/neuregulin-dependent-regulation-of-fast-spiking-interneuron-excitability-controls-the-timing-of-the-critical-period
#16
Yu Gu, Trinh Tran, Sachiko Murase, Andrew Borrell, Alfredo Kirkwood, Elizabeth M Quinlan
: Maturation of excitatory drive onto fast-spiking interneurons (FS INs) in the visual cortex has been implicated in the control of the timing of the critical period for ocular dominance plasticity. However, the mechanisms that regulate the strength of these synapses over cortical development are not understood. Here we use a mouse model to show that neuregulin (NRG) and the receptor tyrosine kinase erbB4 regulate the timing of the critical period. NRG1 enhanced the strength of excitatory synapses onto FS INs, which inhibited ocular dominance plasticity during the critical period but rescued plasticity in transgenics with hypoexcitable FS INs...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27646261/myelination-of-parvalbumin-interneurons-a-parsimonious-locus-of-pathophysiological-convergence-in-schizophrenia
#17
J Stedehouder, S A Kushner
Schizophrenia is a debilitating psychiatric disorder characterized by positive, negative and cognitive symptoms. Despite more than a century of research, the neurobiological mechanism underlying schizophrenia remains elusive. White matter abnormalities and interneuron dysfunction are the most widely replicated cellular neuropathological alterations in patients with schizophrenia. However, a unifying model incorporating these findings has not yet been established. Here, we propose that myelination of fast-spiking parvalbumin (PV) interneurons could be an important locus of pathophysiological convergence in schizophrenia...
September 20, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27629860/myoclonus-epilepsy-and-ataxia-due-to-potassium-channel-mutation-meak-is-caused-by-heterozygous-kcnc1-mutations
#18
Fábio A Nascimento, Danielle M Andrade
Progressive myoclonus epilepsy (PME) is a distinct group of seizure disorders characterized by gradual neurological decline with ataxia, myoclonus and recurring seizures. There are several forms of PME, among which the most recently described is MEAK - myoclonus epilepsy and ataxia due to potassium channel mutation. This particular subtype is caused by a recurrent de novo heterozygous mutation (c.959G>A, p.Arg320His) in the KCNC1 gene, which maps to chromosome 11 and encodes for the Kv3.1 protein (a subunit of the Kv3 subfamily of voltage-gated potassium channels)...
September 1, 2016: Epileptic Disorders: International Epilepsy Journal with Videotape
https://www.readbyqxmd.com/read/27628208/social-context-differentially-modulates-activity-of-two-interneuron-populations-in-an-avian-basal-ganglia-nucleus
#19
Sarah Cushing Woolley
Basal ganglia circuits are critical for the modulation of motor performance across behavioral states. In zebra finches, a cortical-basal ganglia circuit dedicated to singing is necessary for males adjust their song performance and transition between spontaneous singing, when they are alone ('undirected' song), and a performance state when they sing to a female ('female-directed song'). However, we know little about the role of different basal ganglia cell types in this behavioral transition or the degree to which behavioral context modulates the activity of different neuron classes...
September 14, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27620551/binge-like-alcohol-exposure-during-adolescence-disrupts-dopaminergic-neurotransmission-in-the-adult-prelimbic-cortex
#20
Heather Trantham-Davidson, Samuel W Centanni, S Corrin Garr, Natasha N New, Patrick J Mulholland, Justin T Gass, Elizabeth J Glover, Stan B Floresco, Fulton T Crews, Harish R Krishnan, Subhash C Pandey, L Judson Chandler
Repeated binge-like exposure to alcohol during adolescence has been reported to perturb prefrontal cortical development, yet the mechanisms underlying these effects are unknown. Here we report that adolescent intermittent ethanol exposure induces cellular and dopaminergic abnormalities in the adult prelimbic cortex (PrL-C). Exposing rats to alcohol during early-mid adolescence (PD28-42) increased the density of long/thin dendritic spines of layer 5 pyramidal neurons in the adult PrL-C. Interestingly, although AIE exposure did not alter the expression of glutamatergic proteins in the adult PrL-C, there was a pronounced reduction in dopamine (DA) D1 receptor modulation of both intrinsic firing and evoked NMDA currents in pyramidal cells, whereas D2 receptor function was unaltered...
September 13, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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