Presynaptic, extrasynaptic and axonal GABAA receptors in the CNS: where and why?
Although GABA(A) receptors are widely distributed at inhibitory synapses on dendrites and cell bodies of neurons, they also occur in other places, in particular at synapses made on axons and in extrasynaptic membranes. This review summarises some of the evidence that presynaptic receptors modulate transmission not only at primary afferents in the spinal cord, but also at a variety of sites in the brain, including hippocampal mossy fibres. These receptors modulate transmitter release via several different mechanisms. Another form of unconventional GABA(A) receptor-mediated signalling is the mediation of a tonic conductance, seen in granule cells of the cerebellum and dentate gyrus and also in hippocampal interneurons. Tonic signalling appears to be mediated by extrasynaptic receptors. The adaptive significance of this form of signalling remains poorly understood.
Kullmann
Dimitri M
DM
Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK. d.kullmann@ion.ucl.ac.uk
Ruiz
Arnaud
A
Rusakov
Dmitri M
DM
Scott
Ricardo
R
Semyanov
Alexey
A
Walker
Matthew C
MC
D000222:Adaptation, Physiological; D000344:Afferent Pathways / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism; D020013:Calcium Signaling; D002490:Central Nervous System / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism; D006801:Humans; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism; D015398:Signal Transduction; D009435:Synaptic Transmission
D011963:Receptors, GABA-A; D017661:Receptors, Presynaptic