Central Role of GABA in Neuron–Glia Interactions

Abstract

The major types of glial cells-astrocytes, microglia, and cells of the oligodendroglial lineage-are known to express functional metabotropic and ionotropic GABA receptors. Neuronal signaling mechanisms allowing for the activation of these receptors in glia are probably as complex as those described among neurons and involve synaptic and extrasynaptic transmission modes. In addition, astrocytes can signal back to neurons by releasing GABA, probably through unconventional nonvesicular mechanisms. The decryption of the roles played by GABAergic signaling in neuron-glia interactions is only beginning, but it has been suggested that activation of glial cells by GABA influences important functions of the brain such as neuronal activity, differentiation, myelination, and neuroprotection. This review discusses the cellular mechanisms allowing the major types of glial cells to sense and transmit GABAergic signals and gives an overview of potential roles of this signaling pathway in developing and mature brains.

Axon-to-Glia Interaction Regulates GABAAReceptor Expression in Oligodendrocytes

“…This effect might explain the apparent discrepancy observed in previous studies with respect to the benzodiazepine sensitivity of cells from the oligodendroglial lineage since different GABA concentrations were applied. In one case using # EC 30 (Von Blankenfeld et al, 1991), potentiation was reported for FZP, and in other cases applying GABA $ EC 50 , no effect was observed for FZP (Williamson et al, 1998) or DZP (Bronstein et al, 1998) (see also Vélez-Fort et al, 2012). Nonetheless, the presence of the benzodiazepine site in GABA A receptors in OLGs is further supported by the effects of b-carbolines, which are postulated to be endogenous benzodiazepine site modulators (Peña et al, 1986).…”

“…In particular, both OPCs and mature OLGs express the two main subtypes of GABA receptors: GABA A (Hoppe and Kettenmann 1989;Von Blankenfeld et al, 1991;Berger et al, 1992;Cahoy et al, 2008) and GABA B (Luyt et al, 2007). Sensitivity to GABA in mature OLGs is greatly reduced (Berger et al, 1992), which suggests a specific role for GABA signaling in the development of the oligodendroglial lineage and during the initial stages of myelination and/or axon recognition (Vélez-Fort et al, 2012;Zonouzi et al, 2015). However, there is no detailed information about the status and fate of the different receptors and channels in this specific time window when OLGs encounter axons.…”

Heterogeneity in expression of functional ionotropic glutamate and GABA receptors in astrocytes across brain regions: insights from the thalamus

“…GABA A receptors are abundantly found in astrocytes throughout brain regions [27]. In acutely isolated hippocampal astrocytes, receptor currents were inhibited by bicuculline and picrotoxin, potentiated by pentobarbital and diazepam, while the inverse agonist methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) mostly decreased the responses.…”

Localization of SUCLA2 and SUCLG2 subunits of succinyl CoA ligase within the cerebral cortex suggests the absence of matrix substrate-level phosphorylation in glial cells of the human brain

“…The enzymes required for a complete 'GABA shunt' are present in glial cells in the adult human brain; astrocytes express glutamate dehydrogenase (both isoforms 1 and 2, see below) (Spanaki et al 2014), GAD67 (but not GAD65), GABA-T as well as the GABA A and GABA B receptors (Lee et al 2011a;Schwab et al 2013) reviewed in (Velez-Fort et al 2012). The intensity of immunostaining for GAD67 and GABA-T in these cells is comparable or greater to that observed for known inhibitory neurons.…”