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Open AccessJournal ArticleDOI

Compartmentalization of GABAergic Inhibition by Dendritic Spines

TLDR
The findings suggest that the effect of an inhibitory synapse can be as compartmentalized as that of an excitatory synapse, provided that the synapses are localized on spine heads.
Abstract
γ-aminobutyric acid-mediated (GABAergic) inhibition plays a critical role in shaping neuronal activity in the neocortex. Numerous experimental investigations have examined perisomatic inhibitory synapses, which control action potential output from pyramidal neurons. However, most inhibitory synapses in the neocortex are formed onto pyramidal cell dendrites, where theoretical studies suggest they may focally regulate cellular activity. The precision of GABAergic control over dendritic electrical and biochemical signaling is unknown. By using cell type-specific optical stimulation in combination with two-photon calcium (Ca(2+)) imaging, we show that somatostatin-expressing interneurons exert compartmentalized control over postsynaptic Ca(2+) signals within individual dendritic spines. This highly focal inhibitory action is mediated by a subset of GABAergic synapses that directly target spine heads. GABAergic inhibition thus participates in localized control of dendritic electrical and biochemical signaling.

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GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits

TL;DR: Current understanding of neocortical interneuron diversity and the properties that distinguish cell types are reviewed and it is illustrated how recent advances in the field have shed light onto the mechanisms by which GABAergic inhibition contributes to network operations.
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Principles of connectivity among morphologically defined cell types in adult neocortex

TL;DR: This comprehensive profiling of neuronal cell types and connections in adult neocortex provides the most complete wiring diagram of neocortical microcircuits to date and should aid efforts to identify specific circuit abnormalities in animal models of brain disease and may eventually provide a path toward the development of comprehensive circuit-based, cell type–specific interventions.
Journal ArticleDOI

Cation-chloride cotransporters in neuronal development, plasticity and disease

TL;DR: This work has shown that one family of ion transporters, cation-chloride cotransporters (CCCs), and in particular K+–Cl− cOTransporter 2 (KCC2), have seminal roles in shaping GABAergic signalling and neuronal connectivity.
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Altered connectivity in depression: GABA and glutamate neurotransmitter deficits and reversal by novel treatments

TL;DR: These studies demonstrate that depression and chronic stress exposure cause atrophy of neurons in cortical and limbic brain regions implicated in depression, and brain imaging studies demonstrate altered connectivity and network function in the brains of depressed patients.
Journal ArticleDOI

Amygdala interneuron subtypes control fear learning through disinhibition

TL;DR: It is demonstrated that associative learning is dynamically regulated by the stimulus-specific activation of distinct disinhibitory microcircuits through precise interactions between different subtypes of local interneurons.
References
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Journal ArticleDOI

A robust and high-throughput Cre reporting and characterization system for the whole mouse brain

TL;DR: A set of Cre reporter mice with strong, ubiquitous expression of fluorescent proteins of different spectra is generated and enables direct visualization of fine dendritic structures and axonal projections of the labeled neurons, which is useful in mapping neuronal circuitry, imaging and tracking specific cell populations in vivo.
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The NEURON simulation environment

TL;DR: This work presents the basic ideas that would help informed users make the most efficient use of NEURON, the powerful and flexible environment for implementing models of individual neurons and small networks of neurons.
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Structural basis of long-term potentiation in single dendritic spines

TL;DR: The results indicate that spines individually follow Hebb's postulate for learning and suggest that small spines are preferential sites for long-term potentiation induction, whereas large spines might represent physical traces of long- term memory.
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Model of autism: increased ratio of excitation/inhibition in key neural systems

TL;DR: In this paper, a model that postulates that some forms of autism are caused by an increased ratio of excitation/inhibition in sensory, mnemonic, social and emotional systems is proposed.
Journal ArticleDOI

A Resource of Cre Driver Lines for Genetic Targeting of GABAergic Neurons in Cerebral Cortex

TL;DR: Using genetic engineering in mice, approximately 20 Cre and inducible CreER knockin driver lines that reliably target major classes and lineages of GABAergic neurons are generated, thereby enabling a systematic and comprehensive analysis from cell fate specification, migration, and connectivity, to their functions in network dynamics and behavior.
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