Tonically active GABA A receptors: modulating gain and maintaining the tone.

By Alexey Semyanov, M. Walker, D. Kullmann, R. Silver. Trends in Neurosciences, 2004

784 citations recorded by the source corpus.

GABAA receptors not only respond to the local release of GABA from presynaptic terminals, but can also mediate a persistent 'tonic current'. This reflects the activation of high-affinity GABAA receptors by ambient GABA concentrations. Tonic GABAA-receptor-mediated signalling occurs in different brain regions, shows cell-type-specific differences in magnitude and pharmacology, and changes during brain development. Some clues to the adaptive significance of this phenomenon are beginning to emerge: in cerebellar granule cells, it alters the gain of transmission of rate-coded sensory information; in the hippocampus, it acts in a cell-type-specific manner to regulate the excitability of the network. Because tonic conductances can be modulated by changes in GABA release and uptake, and by modulators of high-affinity GABAA receptors including neurosteroids, this phenomenon provides a potentially important new window onto neuronal information processing and pathological states such as epilepsy.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/ff760decd8b2329a2295db00e0c25deaad703cba

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Citations in the corpus

Extrasynaptic GABAA receptors: Their function in the CNS and implications for disease (2012, background): “…generate a tonic conductance that regulates the excitability of pyramidal neurons in CA1 and CA3 regions of the hippocampus (Caraiscos et al., 2004; Glykys andMody, 2006, 2007; Pavlov et al., 2009; Prenosil et al., 2006; Semyanov et al., 2004) and layer 5 cortical neurons (Yamada et al., 2007).”
RNA editing produces glycine receptor α3P185L, resulting in high agonist potency (2005, neutral): “25), NaHCO3 (25), CaCl2 (2), and MgCl2 (1).”
Properties of Somatosensory Synaptic Integration in Cerebellar Granule Cells In Vivo (2006, background): “…sparse coding in granule cells have heavily influenced current models about the function of the cerebellar granule layer (Marr, 1969; Albus, 1971; Tyrrell and Willshaw, 1992; Houk et al., 1996; Schweighofer et al., 1998, 2001; Wolpert et al., 1998; Chadderton et al., 2004; Semyanov et al., 2004).”
SLC6 Neurotransmitter Transporters: Structure, Function, and Regulation (2011, background): “Inhibition of synaptic GABA uptake increases synaptic GABA concentrations and promotes enhanced strength and duration of inhibitory signals (Semyanov et al., 2003, 2004; Gether et al., 2006).”
Hippocampal sharp wave‐ripple: A cognitive biomarker for episodic memory and planning (2015, background): “Synaptic GABAA receptors mediate transient effects through phasic actions, whereas extrasynaptic GABAA receptors produce more prolonged (tonic) changes in the membrane potential and conductance, thereby affecting excitability (Semyanov et al., 2004; Kullmann et al., 2005; Farrant and Kaila, 2007).”
International Union of Pharmacology. LXX. Subtypes of γ-Aminobutyric AcidA Receptors: Classification on the Basis of Subunit Composition, Pharmacology, and Function. Update (2008, background): “The physiological and pharmacological importance of perisynaptically and extrasynaptically localized GABA A -Rs has recently become increasingly appreciated (Mody and Pearce, 2004; Semyanov et al., 2004; Farrant and Nusser, 2005).”