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| Open AccessPrefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention
VIP interneurons have been shown to disinhibit pyramidal neurons by inhibiting other interneuron types. Here, the authors report that ChAT-VIP subtype of interneurons directly excite pyramidal neurons in multiple layers via fast cholinergic neurotransmission.
- Joshua Obermayer
- , Antonio Luchicchi
- & Huibert D. Mansvelder
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Article
| Open AccessNeurons in the Nucleus papilio contribute to the control of eye movements during REM sleep
Rapid eye movement (REM) sleep is a sleep phase characterised by random eye movements for which the underlying motor commands are yet to be revealed. The authors describe that a cluster of medulla oblongata neurons in the Nucleus papiliocontributes to the control of eye movements during REM sleep.
- C. Gutierrez Herrera
- , F. Girard
- & M. R. Celio
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| Open AccessEmbryonic progenitor pools generate diversity in fine-scale excitatory cortical subnetworks
Glutamatergic neurons in the mammalian cortex are born from a heterogeneous pool of embryonic progenitors, however, it is unclear how these different progenitors contribute to diversity within the mature cortex. In this study, authors combine in utero progenitor labeling techniques with targeted Patch-Seq methods and high resolution synaptic circuit mapping in the mature mouse cortex to show that intermediate progenitors can generate restricted sets of transcriptomically-defined glutamatergic neurons that have distinct patterns of local and long-range synaptic connections.
- Tommas J. Ellender
- , Sophie V. Avery
- & Colin J. Akerman
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| Open AccessA thalamocortical pathway for fast rerouting of tactile information to occipital cortex in congenital blindness
In congenitally blind people, tactile stimuli can activate the occipital (visual) cortex. Here, the authors show using magnetoencephalography (MEG) that occipital activation can occur within 35 ms following tactile stimulation, suggesting the existence of a fast thalamocortical pathway for touch in congenitally blind humans.
- Franziska Müller
- , Guiomar Niso
- & Ron Kupers
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Article
| Open AccessHypothalamus-hippocampus circuitry regulates impulsivity via melanin-concentrating hormone
Impulsive behaviour is common in various neuropsychiatric disorders. Here, the authors identify a pathway from the lateral hypothalamus to the ventral hippocampus and the role of melanin-concentrating hormone signaling in these neurons in specifically regulating impulsivity.
- Emily E. Noble
- , Zhuo Wang
- & Scott E. Kanoski
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| Open AccessComputing by modulating spontaneous cortical activity patterns as a mechanism of active visual processing
The brain’s cortex shows complex activity patterns in the absence of sensory inputs. Here, using computational modelling, the authors demonstrate that cortical spontaneous activity is modulated by sensory input and that this modulation process underlies active visual processing.
- Guozhang Chen
- & Pulin Gong
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Article
| Open AccessGenetic mapping and evolutionary analysis of human-expanded cognitive networks
Several cortical association areas have rapidly expanded in size during human evolution, including elements of the central cognitive default mode network (DMN). Here, the authors show that genes highly divergent between humans and other primates (HAR genes) are particularly expressed in these brain regions.
- Yongbin Wei
- , Siemon C. de Lange
- & Martijn P. van den Heuvel
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Article
| Open AccessRevealing neural correlates of behavior without behavioral measurements
Neuronal tuning is typically measured in response to a priori defined behavioural variables of interest. Here, the authors use an unsupervised learning approach to recover neuronal tuning with respect to the recorded network activity and show that this can reveal the relevant behavioural variables.
- Alon Rubin
- , Liron Sheintuch
- & Yaniv Ziv
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Article
| Open AccessRapid single-wavelength lightsheet localization microscopy for clarified tissue
It has been challenging to perform super-resolution imaging in large volumes due to aberrations encountered. Here, the authors combine single-wavelength Bessel lightsheet localization microscopy with tissue clearing techniques and image neurons across the whole brain of adult fruit flies.
- Li-An Chu
- , Chieh-Han Lu
- & Bi-Chang Chen
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Article
| Open AccessHigh-potency ligands for DREADD imaging and activation in rodents and monkeys
Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a powerful tool for neuroscience, but the standard DREADD ligand, CNO, has significant drawbacks. Here the authors report two novel high-potency DREADD ligands and a novel DREADD radiotracer for imaging purposes.
- Jordi Bonaventura
- , Mark A. G. Eldridge
- & Michael Michaelides
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Article
| Open AccessCharacterization of transgenic mouse models targeting neuromodulatory systems reveals organizational principles of the dorsal raphe
In addition to serotonin neurons, the dorsal raphe nucleus (DR) also contains dopamine, glutamate, and GABA neurons. Here, the authors systematically compare the neurochemical identity, cell type specificity, anatomical distribution, and connectivity of DR cells targeted by commonly used Cre lines.
- Daniel F. Cardozo Pinto
- , Hongbin Yang
- & Stephan Lammel
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Article
| Open AccessHypothalamic neuronal circuits regulating hunger-induced taste modification
Hunger modulates perception of good and bad tastes. Here, the authors report that orexigenic AgRP neurons in the hypothalamus mediate these effects through glutamatergic lateral hypothalamic neurons that send distinct projections to the lateral septum and lateral habenula.
- Ou Fu
- , Yuu Iwai
- & Ken-ichiro Nakajima
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Article
| Open AccessCell type-specific modulation of sensory and affective components of itch in the periaqueductal gray
The supraspinal mechanisms involved in itch specific sensation are not well understood. Here the authors identify a subpopulation of neurons in the periaqueductal gray that modulate chronic itch in rodents
- Vijay K. Samineni
- , Jose G. Grajales-Reyes
- & Robert W. Gereau IV
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Article
| Open AccessPlasticity in striatal dopamine release is governed by release-independent depression and the dopamine transporter
Dopamine release in the striatum has important roles in action selection and in disorders such as Parkinson’s disease. The authors here show that short-term plasticity of dopamine release is strongly determined by axonal activation and dopamine transporters.
- Mark D. Condon
- , Nicola J. Platt
- & Stephanie J. Cragg
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Article
| Open AccessInferring neural signalling directionality from undirected structural connectomes
Neural signalling is directional, but non-invasive neuroimaging methods are unable to map directed connections between brain regions. Here, the authors show how network communication measures can be used to infer signalling directionality from the undirected topology of brain structural connectomes.
- Caio Seguin
- , Adeel Razi
- & Andrew Zalesky
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Article
| Open AccessHierarchical control of locomotion by distinct types of spinal V2a interneurons in zebrafish
V2a excitatory interneurons in the spinal cord are important for coordinating locomotion. Here the authors describe two types of V2a neuron with differences in higher order and lower order connectivity in larval zebrafish.
- Evdokia Menelaou
- & David L. McLean
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Article
| Open AccessLayer 4 of mouse neocortex differs in cell types and circuit organization between sensory areas
Layer 4 of the mammalian neocortex is important for cortical information processing but its cellular composition and local circuits remains elusive. The authors compared two primary sensory cortical areas of mice and found differences in cell composition and local connectivity.
- Federico Scala
- , Dmitry Kobak
- & Andreas Savas Tolias
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Article
| Open AccessRole of laterodorsal tegmentum projections to nucleus accumbens in reward-related behaviors
The laterodorsal tegmental nucleus (LDT) is known to influence reward processing through its projections to the VTA. Here, the authors report that the cholinergic projections from the LDT to the nucleus accumbens play an important role in motivation and positive reinforcement behaviors.
- Bárbara Coimbra
- , Carina Soares-Cunha
- & Ana João Rodrigues
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| Open AccessA GABAergic and peptidergic sleep neuron as a locomotion stop neuron with compartmentalized Ca2+ dynamics
The GABAergic and peptidergic neuron RIS mediates sleep in Caenorhabditis elegans. The authors demonstrated here that RIS also functions as a locomotion stop neuron. Its optogenetic stimulation caused acute and persistent inhibition of locomotion, and brief intrinsic RIS activity preceded slowing.
- Wagner Steuer Costa
- , Petrus Van der Auwera
- & Alexander Gottschalk
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Article
| Open AccessMuscarinic acetylcholine receptor signaling generates OFF selectivity in a simple visual circuit
Drosophila larvae are able to perform visually-guided behaviours yet the molecular and circuit mechanisms for discriminating changes in light intensity are not known. Here, the authors report that ON versus OFF discrimination results from opposing cholinergic and glutamatergic mechanisms.
- Bo Qin
- , Tim-Henning Humberg
- & Quan Yuan
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Article
| Open AccessNeural sensitization improves encoding fidelity in the primate retina
Light intensity on the retina can fluctuate rapidly during natural vision, posing a challenge for encoding visual information. Here, the authors report that mechanisms of sensitization/facilitation maintain the sensitivity of the numerically dominant neural pathway in the primate retina during dynamic vision.
- Todd R. Appleby
- & Michael B. Manookin
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Article
| Open AccessPropagation of temporal and rate signals in cultured multilayer networks
The nature of the signals that propagate through feedforward networks is not well understood. Here, the authors combine microfabrication, multilayer cortical cultures, and optogenetic stimulation to show that NMDA-mediated synaptic current generates a sustained phase of activity that propagates firing rate signals.
- Jérémie Barral
- , Xiao-Jing Wang
- & Alex D. Reyes
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| Open AccessA null model of the mouse whole-neocortex micro-connectome
A combination of large-scale connectomics with cellular and synapse data to generate a first draft statistical model of the neuron-to-neuron micro-connectome of a whole mouse neocortex. This micro-connectome recreates biological trends of targeting on the macro-, meso-, and micro-scale.
- Michael W. Reimann
- , Michael Gevaert
- & Eilif Muller
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Article
| Open AccessGlia-neuron interactions underlie state transitions to generalized seizures
During epileptic seizures, neural activity across the brain switches into a hyperactive and hypersynchronized state. Here, the authors report on the role of glia-glia and glia-neuron interactions in mediating the changes that result in the ictal state in a zebrafish model of epilepsy.
- Carmen Diaz Verdugo
- , Sverre Myren-Svelstad
- & Emre Yaksi
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Article
| Open AccessMultifunctional multi-shank neural probe for investigating and modulating long-range neural circuits in vivo
Microelectromechanical neural probes can cause tissue damage and often cannot record from distant brain areas. Here the authors combine electrical recording, optical stimulation and microfluidic drug delivery in one multi-shank probe with thinner shanks to reduce damage and a flexible design to target long-range neural circuits.
- Hyogeun Shin
- , Yoojin Son
- & Il-Joo Cho
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Article
| Open AccessCortical reliability amid noise and chaos
Whether cortical neurons can fire reliable spikes amid cellular noise and chaotic network dynamics remains debated. Here the authors simulate a detailed neocortical microcircuit model and show that noisy and chaotic cortical network dynamics are compatible with stimulus-evoked, millisecond spike-time reliability.
- Max Nolte
- , Michael W. Reimann
- & Eilif B. Muller
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Article
| Open AccessMemory-guided microsaccades
Microsaccades are small-amplitude, fixational eye movements that are largely thought to be involuntary. Here, the authors demonstrate that monkeys (and humans) can be easily trained to respond to a remembered target location with a volitional microsaccade, and that a population of superior colliculus neurons is selectively associated with them.
- Konstantin F. Willeke
- , Xiaoguang Tian
- & Ziad M. Hafed
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Article
| Open AccessSensory cortex wiring requires preselection of short- and long-range projection neurons through an Egr-Foxg1-COUP-TFI network
Layer 4 spiny stellate cells project locally while pyramidal neurons have long-range projections yet the molecular program that determines their specificity is not yet known. Here, the authors demonstrate that Egr, Foxg1 and COUP-TFI transcription factors play causal role in the specification of these cell types.
- Pei-Shan Hou
- , Goichi Miyoshi
- & Carina Hanashima
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Article
| Open AccessClass IIa HDACs regulate learning and memory through dynamic experience-dependent repression of transcription
The molecular mechanisms of memory storage remain poorly understood. In this study, authors describe a new mechanism that regulates the cellular patterns of early response gene signaling during learning via the recruitment of two functionally redundant nuclear repressors, class IIa histone deacetylases (HDACs) 4 and 5
- Yongchuan Zhu
- , Min Huang
- & Anton Maximov
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Article
| Open AccessTarget specific functions of EPL interneurons in olfactory circuits
The precise cell-type specific role of inhibitory interneurons in regulating sensory responses in the olfactory bulb is not known. Here, the authors report that removing GABAergic inhibition from one layer differentially affects response dynamics of the two main output cell types and changes odor mixture processing.
- Gary Liu
- , Emmanouil Froudarakis
- & Benjamin R. Arenkiel
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| Open AccessPlasticity versus stability across the human cortical visual connectome
It is thought that higher cortical areas are more plastic than lower ones, but there is little direct evidence for this. Here, the authors show that plasticity (defined as lower heritability) of functional connectivity decreases from early to mid-level visual cortex, and then increases further up the visual hierarchy.
- Koen V. Haak
- & Christian F. Beckmann
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Article
| Open AccessReward signaling in a recurrent circuit of dopaminergic neurons and peptidergic Kenyon cells
Olfactory information from Kenyon cells in the mushroom body and reward information from pPAM dopaminergic neurons is required for appetitive olfactory learning and memory. Here, the authors report evidence for a feedback circuit mechanism between Kenyon cells and pPAM neurons for reward memory that involves short neuropeptide F.
- Radostina Lyutova
- , Mareike Selcho
- & Dennis Pauls
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Article
| Open AccessNeurons in primary auditory cortex represent sound source location in a cue-invariant manner
The brain's auditory cortex is involved not just in detection of sounds, but also in localizing them. Here, the authors show that neurons in ferret primary auditory cortex (A1) encode the location of sound sources, as opposed to merely reflecting spatial cues.
- Katherine C. Wood
- , Stephen M. Town
- & Jennifer K. Bizley
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Article
| Open AccessDecoupling of timescales reveals sparse convergent CPG network in the adult spinal cord
Spinal CPGs transmit movement commands through rhythmic synaptic drive onto the spinal premotor network. Here, the authors use paired recordings to demonstrate that spinal neurons have decorrelated synaptic activity suggesting a CPG network with sparse convergent connectivity.
- Marija Radosevic
- , Alex Willumsen
- & Rune W. Berg
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Article
| Open AccessLocus coeruleus-CA1 projections are involved in chronic depressive stress-induced hippocampal vulnerability to transient global ischaemia
Depression and transient ischaemic attacks are tightly regulated but the neural circuits underlying depression-modulated ischaemic injury are not known. Here, the authors show that the locus coeruleus-CA1 pathway is involved in depression-associated ischaemia susceptibility.
- Qian Zhang
- , Dian Xing Hu
- & Bo Tian
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Article
| Open AccessModulation of extrasynaptic GABAA alpha 5 receptors in the ventral hippocampus normalizes physiological and behavioral deficits in a circuit specific manner
Region-specific increases in hippocampal activity have been reported in schizophrenia patients, yet there are little known about how these circuit levels changes modulate behavioral deficits. Here authors found that that over-expression of the a5 subunit of the GABAA receptor increased tonic GABA currents and normalized aberrant pyramidal cell activity in the ventral hippocampus which had distinct disease symptom outcomes depending on the pathway targeted
- J. J. Donegan
- , A. M. Boley
- & D. J. Lodge
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Article
| Open AccessA bed nucleus of stria terminalis microcircuit regulating inflammation-associated modulation of feeding
Inflammation can reduce food intake. Here the authors show that the GABAergic pathway from bed nucleus of stria terminalis to lateral hypothalamus regulates the inflammation induced reduction in feeding in mice.
- Yong Wang
- , JungMin Kim
- & Haijiang Cai
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Article
| Open AccessA striatal interneuron circuit for continuous target pursuit
Many natural behaviours involve tracking of a target in space. Here, the authors describe a task to assess this behaviour in mice and use in vivo electrophysiology, calcium imaging, optogenetics, and chemogenetics to investigate the role of the striatum in target pursuit.
- Namsoo Kim
- , Haofang E. Li
- & Henry H. Yin
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Article
| Open AccessOrchestrated ensemble activities constitute a hippocampal memory engram
The brain stores memories through a set of neurons known as engram cells. Here, the authors show that engram cells in the mouse hippocampus are organized into sub-ensembles representing distinct pieces of information, which are then orchestrated to constitute an entire memory.
- Khaled Ghandour
- , Noriaki Ohkawa
- & Kaoru Inokuchi
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Article
| Open AccessNeuronal cell-subtype specificity of neural synchronization in mouse primary visual cortex
Synchronised neuronal activity is essential for cortical function, yet mechanistic insights into this process remain limited. Here, authors use a combination of in vivo imaging and targeted whole-cell recordings to demonstrate that Somatostatin neurons, in the superficial layers of the mouse primary visual cortex, exhibit functional heterogeneity and can be classified into two distinct subtypes characterized as either having type I uncorrelated, or type II highly correlated with network activity.
- Ulf Knoblich
- , Lawrence Huang
- & Lu Li
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Article
| Open AccessNeural mechanisms of contextual modulation in the retinal direction selective circuit
The mechanisms of contextual modulation in direction selective ganglion cells in the retina remain unclear. Here, the authors find that that On-Off direction-selective ganglion cells are differentially sensitive to discontinuities of dark and bright moving edges in the visual environment and, using synapse-specific genetic manipulations with functional measurements, reveal the microcircuits underlying this contextual sensitivity.
- Xiaolin Huang
- , Melissa Rangel
- & Wei Wei
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Article
| Open AccessIndividual variability in behavior and functional networks predicts vulnerability using an animal model of PTSD
How do individual differences affect vulnerability to developing post-traumatic stress disorder (PTSD)? Here, using longitudinal testing in a rat model of PTSD, the authors show patterns of pre-trauma brain connectivity and behaviors that predict PTSD-like responses to trauma exposure.
- David Dopfel
- , Pablo D. Perez
- & Nanyin Zhang
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Article
| Open AccessMemory strength gates the involvement of a CREB-dependent cortical fear engram in remote memory
Little is known about mechanisms that regulate the involvement of cortical engram cells in remote memory. Here, authors demonstrate that memory consolidation by mPFC engram cells requires CREB-mediated transcription, with the functionality of this network hub being gated by memory strength.
- Mariana R. Matos
- , Esther Visser
- & Michel C. van den Oever
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Article
| Open AccessA neural circuit model of decision uncertainty and change-of-mind
We make decisions with varying degrees of confidence and, if our confidence in a decision falls, we may change our mind. Here, the authors present a neuronal circuit model to account for how change of mind occurs under particular low-confidence conditions.
- Nadim A. A. Atiya
- , Iñaki Rañó
- & KongFatt Wong-Lin
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Article
| Open AccessRegulation of locomotor speed and selection of active sets of neurons by V1 neurons
During evoked swims, zebrafish larvae transition from fast to slow speeds. Here, the authors elucidate the circuit mechanisms in the central pattern generators in the spinal cord and show that genetically labeled V1 spinal interneurons provide in phase inhibition onto fast and slow motor neurons that are involved in the switching behaviour.
- Yukiko Kimura
- & Shin-ichi Higashijima
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Article
| Open AccessDynamic assembly of ribbon synapses and circuit maintenance in a vertebrate sensory system
Ribbon synapses in our sensory nervous system are central to hearing and sight, yet little is known about how these synapses are assembled and maintained during development. In this study, authors use live imaging techniques to monitor ribbon appearance, loss and maintenance in a retinal circuit during development to show that nascent synapses comprising of both ribbons and PSD95 are more stable over time compared to contacts without ribbons.
- Haruhisa Okawa
- , Wan-Qing Yu
- & Rachel O. L. Wong
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Article
| Open AccessIdentification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies
The wiring of peripheral neural circuits that regulate heart rate is poorly understood. In this study, authors used tissue clearing for high-resolution characterization of nerves in the heart in 3D and transgenic and novel viral vector approaches to identify peripheral parasympathetic and sympathetic neuronal populations involved in heart rate control in mice.
- Pradeep S. Rajendran
- , Rosemary C. Challis
- & Kalyanam Shivkumar
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Article
| Open AccessGlutamate spillover in C. elegans triggers repetitive behavior through presynaptic activation of MGL-2/mGluR5
Katz and colleagues examine glutamate spillover effects on C. elegans behaviour. They show that impaired synaptic glutamate clearance in glial glutamate transporter mutants, causes presynaptic mgl-2/mGluR5 activation, generating postsynaptic neural activity oscillations driving repetitive behaviour.
- Menachem Katz
- , Francis Corson
- & Shai Shaham
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Article
| Open AccessImpaired cortico-striatal excitatory transmission triggers epilepsy
Spike and wave discharge (SWD) activity is seen during absence seizures and is thought to be thalamocortical in origin. Here, the authors show that SWDs are initiated through the impaired corticostriatal excitatory transmissions onto striatal fast spiking interneurons.
- Hiroyuki Miyamoto
- , Tetsuya Tatsukawa
- & Kazuhiro Yamakawa