Novel functions of GABA signaling in adult neurogenesis

Abstract

Neurotransmitter gamma-aminobutiric acid (GABA) through ionotropic GABAA and metabotropic GABAB receptors plays key roles in modulating the development, plasticity and function of neuronal networks. GABA is inhibitory in mature neurons but excitatory in immature neurons, neuroblasts and neural stem/progenitor cells (NSCs/NPCs). The switch from excitatory to inhibitory occurs following the development of glutamatergic synaptic input and results from the dynamic changes in the expression of Na+/K+/2Cl− co-transporter NKCC1 driving Cl− influx and neuron-specific K+/Cl− co-transporter KCC2 driving Cl− efflux. The developmental transition of KCC2 expression is regulated by Disrupted-in-Schizophrenia 1 (DISC1) and brain-derived neurotrophic factor (BDNF) signaling. The excitatory GABA signaling during early neurogenesis is important to the activity/experience-induced regulation of NSC quiescence, NPC proliferation, neuroblast migration and newborn neuronal maturation/functional integration. The inhibitory GABA signaling allows for the sparse and static functional networking essential for learning/memory development and maintenance.

Decreasing the Expression of GABAA α5 Subunit-Containing Receptors Partially Improves Cognitive, Electrophysiological, and Morphological Hippocampal Defects in the Ts65Dn Model of Down Syndrome

“…Because GABAA receptors regulate the proliferation, migration, differentiation and integration of new neurons [88][89][90][91][92], the decrease in the GABAA mediatedinhibition in the TS mouse after knocking out the Gabra5 gene could play a role in the procognitive effects found in the TS animals by reducing functional and/or neuromorphological anomalies in their hippocampi. Tonic depolarizing GABAA responses by GABAergic Parvalbumin interneurons negatively regulate adult neurogenesis in the dentate gyrus (DG) of the hippocampus [93][94][95].…”

Functions and Dysfunctions of Adult Hippocampal Neurogenesis

“…Notably, newborn neurons exhibit initial depolarizing responses to GABA, which gradually shift to hyperpolarizing responses within two to three weeks of birth (Ge et al 2006, Overstreet Wadiche et al 2005). Depolarizing GABAergic signaling promotes survival, maturation, and synapse formation and activation in newborn neurons (Chancey et al 2013, Ge et al 2006, Pontes et al 2013, Song et al 2013, Tozuka et al 2005). Initial GABAergic synaptic inputs are not sufficient to elicit action potentials and are therefore unlikely to be directly involved in information processing.…”

Development of corticospinal motor excitability and cortical silent period from mid-childhood to adulthood – a navigated TMS study

“…This information cannot be obtained with any other neuroimaging methodologies [29]. Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the CNS and has a central role in a wide variety of physiological and biochemical processes regulation of cognition [45], memory and learning [27], circadian rhythms [1], neural development [60], adult neurogenesis [52], and motor function [23] including motor learning [75]. GABA has an elementary and homeostatic, possibly also compensatory role for intrinsic motor excitability [22].…”