Cellular Mechanisms Contributing to the Functional Heterogeneity of GABAergic Synapses

Abstract

GABAergic inhibitory neurotransmission contributes to diverse aspects of brain development and adult plasticity, including the expression of complex cognitive processes. This is afforded for in part by the dynamic adaptations occurring at inhibitory synapses, which show great heterogeneity both in terms of upstream signaling and downstream effector mechanisms. Single-particle tracking and live imaging have revealed that complex receptor-scaffold interactions critically determine adaptations at GABAergic synapses. Super-resolution imaging studies have shown that protein interactions at synaptic sites contribute to nano-scale scaffold re-arrangements through post-translational modifications (PTMs), facilitating receptor and scaffold recruitment to synaptic sites. Additionally, plasticity mechanisms may be affected by the protein composition at individual synapses and the type of pre-synaptic input. This mini-review article examines recent discoveries of plasticity mechanisms that are operational within GABAergic synapses and discusses their contribution towards functional heterogeneity in inhibitory neurotransmission.

Specific Neuroligin3–αNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampus

“…In central synapses, cell adhesion molecules (CAMs) are major players in trans-synaptic interactions ( de Wit and Ghosh, 2016 ) that serve a primary role in initiating synapse formation by directing contact between axonal and dendritic membranes. Emerging evidence suggests that trans-synaptic interactions are also important for synapse identity, function, plasticity, and maintenance ( Biederer et al, 2017 ; Campbell and Tyagarajan, 2019 ; Südhof, 2017 ). Numerous CAM variants exist due to large gene families and alternative splicing, generating a vast array of possible combinations of pre- and postsynaptic CAMs.…”

Correlation of receptor density and mRNA expression patterns in the human cerebral cortex

“…This discrepancy could be possibly attributed to the most abundant subunits that might mask the real correlation between receptor subunits and their gene expression. Besides subtype variants, for GABA-receptors extensive post-translational modifications have been demonstrated offering an additional venue for effective decoupling of mRNA expression and resulting protein concentration (Campbell and Tyagarajan, 2019).…”

A Specific Neuroligin3-αNeurexin1 Code Regulates GABAergic Synaptic Function in Mouse Hippocampus

“…In central synapses, cell adhesion molecules (CAMs) are major players in trans-synaptic interactions (de Wit & Ghosh, 2016) which serve a primary role in initiating synapse formation by directing contact between axonal and dendritic membranes. Emerging evidence suggests that transsynaptic interactions are also important for synapse identity, function, plasticity and maintenance (Biederer, Kaeser, & Blanpied, 2017;Campbell & Tyagarajan, 2019;. Numerous CAM variants exist due to large gene families and alternative splicing, generating a vast array of possible combinations of pre-and postsynaptic CAMs.…”