The dynamics of GABA signaling: Revelations from the circadian pacemaker in the suprachiasmatic nucleus

Abstract

Virtually every neuron within the suprachiasmatic nucleus (SCN) communicates via GABAergic signaling. The extracellular levels of GABA within the SCN are determined by a complex interaction of synthesis and transport, as well as synaptic and non-synaptic release. The response to GABA is mediated by GABAA receptors that respond to both phasic and tonic GABA release and that can produce excitatory as well as inhibitory cellular responses. GABA also influences circadian control through the exclusively inhibitory effects of GABAB receptors. Both GABA and neuropeptide signaling occur within the SCN, although the functional consequences of the interactions of these signals are not well understood. This review considers the role of GABA in the circadian pacemaker, in the mechanisms responsible for the generation of circadian rhythms, in the ability of non-photic stimuli to reset the phase of the pacemaker, and in the ability of the day-night cycle to entrain the pacemaker.

Neuronal oscillations on an ultra‐slow timescale: daily rhythms in electrical activity and gene expression in the mammalian master circadian clockwork

“…Collectively, most SCN neurons produce the neurotransmitter GABA and express GABA A receptors (Abrahamson & Moore, 2001;Belenky et al, 2008). Here, GABA acts primarily on the GABA A receptors to cause excitation or inhibition in the SCN [see (Albers et al, 2017) for a comprehensive review], presumably coreleased by the SCN peptidergic neurons. As demonstrated by most forms of neuronal synchronisation in the central nervous system, GABA-GABA A receptor signalling in the SCN acts to synchronise the activity of its neurons (Liu & Reppert, 2000;Shirakawa et al, 2000;Aton & Herzog, 2005;Evans et al, 2013;DeWoskin et al, 2015;Myung et al, 2015).…”

“…By contrast, non-photic inputs produce phase shifts in the SCN that differ significantly from those produced by light [see Fig. 1 in (Albers et al, 2017)]. These signals produce large phase advances in behavioural rhythms during the day and small phase delays during the night (Mrosovsky, 1988;Reebs & Mrosovsky, 1989;Mead et al, 1992;Hastings et al, 1998;Lone & Sharma, 2011;Polidarova et al, 2011).…”

The circadian clock: a tale of genetic–electrical interplay and synaptic integration

“…GABA regulates many functions in the SCN, including light-induced phase shifts, synchronization of the dorsal and ventral SCN, and the sensitivity of the circadian clock to light-entraining signals. The specific role of GABA neurotransmission in maintaining cellular synchrony remains controversial (see recent reviews by [23–25]). GABA acts on synaptic GABA A receptors to mediate fast “phasic” signaling between SCN neurons, and extrasynaptic GABA A receptor activation provides SCN cells with a “tonic” GABA A current [26].…”

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].…”