Emerging Mechanisms in Dynamic GABAergic Inhibition

Inhibition is central to all aspects of central nervous system (CNS) function. It is mediated primarily by the neurotransmitter GABA, acting on receptors that are a major target for therapeutics, such as benzodiazepines and neurosteroids. The goal of this Research Topic is to increase our understanding of the fundamental mechanisms contributing to the critical role of inhibitory neurotransmission in normal and abnormal CNS function. The Research Topic contributions will cover: 1- the role of GABAergic transmission during brain development; 2- molecular mechanisms of GABAergic synapse formation and plasticity; 3- the significance of interneuron diversity and their function in specific neuronal circuits; 4- systems approaches to understanding inhibitory neurons function in the brain. Emphasis will be given to new areas of research not covered in detail, for example emerging technologies such as single cell RNA sequencing, synaptic transcriptomics and proteomics in neurodevelopmental disorders and in sleep regulation. A major goal will be to bridge the existing knowledge gap in our understanding of fundamental mechanisms of brain function and of pathophysiology of CNS disorders with emerging concepts about inhibitory neuron function.

The subtopics that will be covered are:

1. GABAAR regulation
2. Biochemistry of gephyrin regulation
3. Novel interaction proteins at GABAergic postsynapses
4. Local Inhibitory-excitatory co-regulation
5. Super resolution understanding of GABAergic postsynapse
6. GABAergic synapse heterogeneity and organization
7. Novel modulators of GABAergic inhibition
8. Systems modulation of GABAergic inhibition
9. Disease mechanisms impinging on GABAergic inhibition

Mini Review articles (3000 words) covering background information, own recent contributions/ discoveries, define questions that require experimental resolution in areas that impact brain function and pathology. One half page image putting together important findings in the topic.