Diversity of GABAergic interneurons and diversification of communication modules in cortical networks

Abstract

The phenotypic diversity of cortical GABAergic neurons is likely necessary for their functional versatility in shaping exquisite spatiotemporal dynamics of circuit operations underlying cognitive processes. Deciphering the logic of this diversity requires overcoming the technical challenge of quantitative and comprehensive analysis of multi-modal cell features as well as the conceptual challenge of formulating a framework of neuronal identity that reflects biological mechanisms and principles. In the past few years, advances in high-throughput single cell analyses began to generate unprecedented datasets on interneuron transcriptomes, morphology and electrophysiology that drive their classification. Recent studies suggest that cardinal interneuron types can be defined by their synaptic communication properties encoded in key transcriptional signatures -a conceptual framework that integrates across phenotypic features and captures neuronal input-output properties elemental to circuit operation. This definition may further facilitate understanding the appropriate granularity of neuron types toward building a biologically-grounded and operationally useful interneuron taxonomy.

Fast and reversible neural inactivation in macaque cortex by optogenetic stimulation of GABAergic neurons

“…A third class of experiments probes the electrophysiological response properties of inhibitory neurons in vivo ( Adesnik et al, 2012 ; Atallah et al, 2012 ; Cardin et al, 2009 ; Scholl et al, 2015 ; Sohal et al, 2009 ; Wilson et al, 2017 ; Wilson et al, 2012 ). Excitatory and inhibitory neurons within a cortical area have different response properties in mice, cats, and ferrets, a fact that is presumably related to differences in their respective functional contributions ( Huang and Paul, 2018 ). Identification of inhibitory and excitatory neurons in vivo has been challenging in monkeys.…”

The Epigenome in Neurodevelopmental Disorders

“…Neuronal circuits of the neocortex are composed of two major types of cortical neurons: excitatory principal neurons expressing glutamate, and the inhibitory γ-aminobutyric acid (GABA)-expressing local interneurons. Although inhibitory interneurons constitute the minority of the entire neuronal population within the cortex with 25-30% in humans and 15-20% in mice, they critically maintain cortical functionality in both species, establishing a balanced equilibrium of cortical excitation and inhibition ( Jones, 2009 ; Huang and Paul, 2018 ; Sultan and Shi, 2018 ).…”