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GABA B receptor‐mediated frequency‐dependent and circadian changes in synaptic plasticity modulate retinal input to the suprachiasmatic nucleus
Author(s) -
Moldavan Mykhaylo G.,
Allen Charles N.
Publication year - 2013
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.248047
Subject(s) - suprachiasmatic nucleus , neuroscience , inhibitory postsynaptic potential , excitatory postsynaptic potential , biology , circadian clock , circadian rhythm , medicine
Key points• Light entrains the circadian clock by activating intrinsically photosensitive retinal ganglion cells projecting axons through the retinohypothalamic tract (RHT) to the hypothalamic suprachiasmatic nucleus (SCN). • Initial release probability and synaptic plasticity changes in RHT‐SCN synapses depended on the strength of GABA B receptor (GABA B R)‐mediated presynaptic inhibition. • The RHT axon terminals are under the tonic inhibitory control of GABA B receptors. CGP55845 (3 μ m ) application increased the evoked excitatory postsynaptic current amplitude 30% throughout the light–dark cycle. • During the light and dark phases the RHT inputs to 55% and 33% of recorded neurons, respectively, were under GABA B inhibitory control indicating that the tonic GABA inhibition contributes to the circadian variation of transmitter release. • GABA B R‐mediated presynaptic inhibition depended on the sensitivity of RHT terminals to GABA B R agonists and diurnal changes of the extracellular GABA concentration around RHT axon terminals in the SCN, and decreased with increasing frequency of RHT stimulation.Abstract Light is the most important environmental signal that entrains the circadian clock located in the hypothalamic suprachiasmatic nucleus (SCN). The retinohypothalamic tract (RHT) was stimulated to simulate the light intensity‐dependent discharges of intrinsically photosensitive retinal ganglion cells projecting axons to the hypothalamus. EPSCs were evoked by paired‐pulse stimulation or by application of stimulus trains, and recorded from SCN neurons in rat brain slices. Initial release probability ( P r ) and synaptic plasticity changes depended on the strength of GABA B receptor (GABA B R)‐mediated presynaptic inhibition and could be different at the same GABA B R agonist concentration. Facilitation caused by frequency‐dependent relief of GABA B R‐mediated inhibition was observed when the initial P r was decreased to less than 15% of control during strong activation of presynaptic GABA B receptors by (±)baclofen (10 μ m ), GABA (≥2 m m ) or by GABA uptake inhibitor nipecotic acid (≥5 m m ). In contrast, short‐term synaptic depression appeared during baclofen (10 μ m ) application when initial P r was greater than 30% of control. Block of 4‐aminopyridine‐sensitive K + currents increased the amplitude and time constant of decay of evoked EPSCs (eEPSCs), and decreased the GABA B R‐mediated presynaptic inhibition. The GABA B receptor antagonist CGP55845 (3 μ m ) increased the eEPSCs amplitude 30% throughout the light−dark cycle. During light and dark phases the RHT inputs to 55% and 33% of recorded neurons, respectively, were under GABA B inhibitory control indicating that the tonic inhibition induced by local changes of endogenous GABA concentration contributes to the circadian variation of RHT transmitter release. We conclude that GABA B R‐mediated presynaptic inhibition decreased with increasing frequency and broadening of presynaptic action potentials, and depended on the sensitivity of RHT terminals to GABA B R agonists, and diurnal changes of the extracellular GABA concentration around RHT axon terminals in the SCN.