Role of tonic GABAergic currents during pre- and early postnatal rodent development

Abstract

In the last three decades it became evident that the GABAergic system plays an essential role for the development of the central nervous system, by influencing the proliferation of neuronal precursors, neuronal migration and differentiation, as well as by controlling early activity patterns and thus formation of neuronal networks. GABA controls neuronal development via depolarizing membrane responses upon activation of ionotropic GABA receptors. However, many of these effects occur before the onset of synaptic GABAergic activity and thus require the presence of extrasynaptic tonic currents in neuronal precursors and immature neurons. This review summarizes our current knowledge about the role of tonic GABAergic currents during early brain development. In this review we compare the temporal sequence of the expression and functional relevance of different GABA receptor subunits, GABA synthesizing enzymes and GABA transporters. We also refer to other possible endogenous agonists of GABAA receptors. In addition, we describe functional consequences mediated by the GABAergic system during early developmental periods and discuss current models about the origin of extrasynaptic GABA and/or other endogenous GABAergic agonists during early developmental states. Finally, we present evidence that tonic GABAergic activity is also critically involved in the generation of physiological as well as pathophysiological activity patterns before and after the establishment of functional GABAergic synaptic connections.

Dihydromyricetin Prevents Fetal Alcohol Exposure-Induced Behavioral and Physiological Deficits: The Roles of GABAA Receptors in Adolescence

“…GABA and GABA A Rs are essential regulators of early brain development and disruption of GABAergic signaling is suspected in numerous neurodevelopmental disorders [73][74][75][76][77][78]. We observed increased anxiety in the EPM and faster onset, as well as longer duration of PTZ-induced seizures after FAE in P25-34 rats (Fig.…”

Differential modulation of phasic and tonic inhibition underlies serotonergic suppression of long-term potentiation in the rat visual cortex

“…Thus, functional discrimination between phasic and tonic inhibition might not be clear in the working network. This is reflected by overlapping control of various neural functions by phasic and tonic inhibition including the regulation of neuronal excitability, learning and memory, sensory processing, neural circuit development, and hippocampal gamma oscillation (Farrant and Nusser, 2005;Prut et al, 2010;Tang et al, 2011;Brickley and Mody, 2012;Kilb et al, 2013). However, since some information requires temporal fidelity in feed-forward networks (Pouille and Scanziani, 2001;Okun and Lampl, 2008), the fast and precise action of phasic inhibition is necessary in addition to the general control of excitability provided by tonic inhibition.…”

Localization of Vesicular Inhibitory Amino Acid Transporter (VIAAT) in the Submandibular Salivary Gland Throughout the Postnatal Development of Mice

“…Since there have been studies suggesting that CREB signalling is a central pathway in adult hippocampal neurogenesis, regulating the development and survival of new hippocampal neurons downstream of GABA-mediated excitation (Fukuchi et al, 2014;Jagasia et al, 2009), the similarity in the chronological localization between CREB and VIAAT/GABA may lead us to consider the possibility that the signalling cascade of the two molecules plays roles in the postnatal development of the salivary glandular cells. In support of this possibility in the peripheral organ, there has recently been accumulating evidence on the role of tonic GABAergic currents during early brain development (Kilb et al, 2013).…”