Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels

Pharmacological Reviews, Год журнала: 2021, Номер 73(4), С. 1469 - 1658

Опубликована: Окт. 1, 2021

Many physiologic effects of l-glutamate, the major excitatory neurotransmitter in mammalian central nervous system, are mediated via signaling by ionotropic glutamate receptors (iGluRs). These ligand-gated ion channels critical to brain function and centrally implicated numerous psychiatric neurologic disorders. There different classes iGluRs with a variety receptor subtypes each class that play distinct roles neuronal functions. The diversity iGluR subtypes, their unique functional properties roles, has motivated large number studies. Our understanding advanced considerably since first subunit gene was cloned 1989, research focus expanded encompass facets biology have been recently discovered exploit experimental paradigms made possible technological advances. Here, we review insights from more than 3 decades studies an emphasis on progress occurred past decade. We cover structure, function, pharmacology, neurophysiology, therapeutic implications for all assembled subunits encoded 18 genes. SIGNIFICANCE STATEMENT: Glutamate important virtually aspects either involved mediating some clinical features neurological disease or represent target treatment. Therefore, pharmacology this will advance our many at molecular, cellular, system levels provide new opportunities treat patients.

Язык: Английский

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GABA-receptive microglia selectively sculpt developing inhibitory circuits

Cell, Год журнала: 2021, Номер 184(15), С. 4048 - 4063.e32

Опубликована: Июль 1, 2021

Язык: Английский

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Interneuron Types as Attractors and Controllers

Annual Review of Neuroscience, Год журнала: 2019, Номер 43(1), С. 1 - 30

Опубликована: Июль 12, 2019

Cortical interneurons display striking differences in shape, physiology, and other attributes, challenging us to appropriately classify them. We previously suggested that interneuron types should be defined by their role cortical processing. Here, we revisit the question of how codify diversity based upon division labor function as controllers information flow. suggest developmental trajectories provide a guide for appreciating argue subtype identity is generated using configurational (rather than combinatorial) code transcription factors produce attractor states underlying gene regulatory network. present our updated three-stage model specification: an initial cardinal step, allocating into few major classes, followed definitive refinement, creating subclasses settling within cortex, lastly, state determination, reflecting incorporation functional circuit ensembles. close discussing findings indicating classes are both evolutionarily ancient conserved. propose complexity circuits phylogenetically old types, complemented evolutionary increase principal neuron diversity. This suggests natural neurobiological definition might derived from match between origin computational function.

Язык: Английский

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Cortical interneurons in autism

Nature Neuroscience, Год журнала: 2021, Номер 24(12), С. 1648 - 1659

Опубликована: Ноя. 29, 2021

Язык: Английский

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An increase of inhibition drives the developmental decorrelation of neural activity

eLife, Год журнала: 2022, Номер 11

Опубликована: Авг. 17, 2022

Throughout development, the brain transits from early highly synchronous activity patterns to a mature state with sparse and decorrelated neural activity, yet mechanisms underlying this process are poorly understood. The developmental transition has important functional consequences, as latter is thought allow for more efficient storage, retrieval, processing of information. Here, we show that, in mouse medial prefrontal cortex (mPFC), during first two postnatal weeks decorrelates following specific spatial patterns. This accompanied by concomitant tilting excitation-inhibition (E-I) ratio toward inhibition. Using optogenetic manipulations network modeling, that phenomena mechanistically linked, relative increase inhibition drives decorrelation activity. Accordingly, mice mimicking etiology neurodevelopmental disorders, subtle alterations E-I associated impairments correlational structure spike trains. Finally, capitalizing on EEG data newborn babies, an analogous takes place also human brain. Thus, changes control (de)correlation and, these means, its imbalance might contribute pathogenesis disorders.

Язык: Английский

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Cortical somatostatin interneuron subtypes form cell-type-specific circuits

Neuron, Год журнала: 2023, Номер 111(17), С. 2675 - 2692.e9

Опубликована: Июнь 29, 2023

Язык: Английский

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The proteomic landscape of synaptic diversity across brain regions and cell types

Cell, Год журнала: 2023, Номер 186(24), С. 5411 - 5427.e23

Опубликована: Ноя. 1, 2023

Neurons build synaptic contacts using different protein combinations that define the specificity, function, and plasticity potential of synapses; however, diversity proteomes remains largely unexplored. We prepared synaptosomes from 7 transgenic mouse lines with fluorescently labeled presynaptic terminals. Combining microdissection 5 brain regions fluorescent-activated synaptosome sorting (FASS), we isolated analyzed 18 synapse types. discovered ∼1,800 unique synapse-type-enriched proteins allocated thousands to types synapses (https://syndive.org/). identify shared modules highlight proteomic hotspots for specialization. reveal common features striatal dopaminergic proteome discover signatures relate functional properties interneuron classes. This study provides a molecular systems-biology analysis framework integrate information subtypes interest cellular or circuit-level experiments.

Язык: Английский

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Neuronal types in the mouse amygdala and their transcriptional response to fear conditioning

Nature Neuroscience, Год журнала: 2023, Номер 26(12), С. 2237 - 2249

Опубликована: Окт. 26, 2023

Abstract The amygdala is a brain region primarily associated with emotional response. use of genetic markers and single-cell transcriptomics can provide insights into behavior-associated cell state changes. Here we present detailed cell-type taxonomy the adult mouse during fear learning memory consolidation. We perform RNA sequencing on naïve fear-conditioned mice, identify 130 neuronal types validate their spatial distributions. A subset all transcriptionally responsive to retrieval. activated engram cells upregulate activity-response genes coordinate expression neurite outgrowth, synaptic signaling, plasticity development. known previously undescribed candidate learning. Our molecular atlas may be used generate hypotheses unveil neuron neural circuits regulating component memory.

Язык: Английский

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Astrocyte-secreted neurocan controls inhibitory synapse formation and function

Neuron, Год журнала: 2024, Номер 112(10), С. 1657 - 1675.e10

Опубликована: Апрель 3, 2024

Astrocytes strongly promote the formation and maturation of synapses by secreted proteins. Several astrocyte-secreted synaptogenic proteins controlling excitatory synapse development were identified; however, those that induce inhibitory synaptogenesis remain elusive. Here, we identify neurocan as an protein. After secretion from astrocytes, is cleaved into N- C-terminal fragments. We found these fragments have distinct localizations in extracellular matrix. The fragment localizes to controls cortical function. Neurocan knockout mice lacking whole protein or only its domain reduced numbers Through super-resolution microscopy, vivo proximity labeling TurboID, astrocyte-specific rescue approaches, discovered somatostatin-positive regulates their formation. Together, our results unveil a mechanism through which astrocytes control circuit-specific mammalian brain.

Язык: Английский

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An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes

Neuron, Год журнала: 2025, Номер 113(10), С. 1525 - 1547.e15

Опубликована: Май 1, 2025

Язык: Английский

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