GABAB receptor-mediated frequency-dependent and circadian changes in synaptic plasticity modulate retinal input to the suprachiasmatic nucleus

J Physiol. 2013 May 15;591(10):2475-90. doi: 10.1113/jphysiol.2012.248047. Epub 2013 Feb 11.


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 (Pr) and synaptic plasticity changes depended on the strength of GABAB receptor (GABABR)-mediated presynaptic inhibition and could be different at the same GABABR agonist concentration. Facilitation caused by frequency-dependent relief of GABABR-mediated inhibition was observed when the initial Pr was decreased to less than 15% of control during strong activation of presynaptic GABAB receptors by (±)baclofen (10 μm), GABA (2 mm) or by GABA uptake inhibitor nipecotic acid (5 mm). In contrast, short-term synaptic depression appeared during baclofen (10 μm) application when initial Pr 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 GABABR-mediated presynaptic inhibition. The GABAB receptor antagonist CGP55845 (3 μm) 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 GABAB 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 GABABR-mediated presynaptic inhibition decreased with increasing frequency and broadening of presynaptic action potentials, and depended on the sensitivity of RHT terminals to GABABR agonists, and diurnal changes of the extracellular GABA concentration around RHT axon terminals in the SCN.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Baclofen / pharmacology
  • Circadian Rhythm / physiology
  • Excitatory Postsynaptic Potentials / drug effects
  • GABA-B Receptor Agonists / pharmacology
  • In Vitro Techniques
  • Male
  • Optic Nerve / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-B / physiology*
  • Retina / physiology*
  • Suprachiasmatic Nucleus / physiology*
  • Synapses / physiology*
  • Synaptic Transmission / drug effects


  • GABA-B Receptor Agonists
  • Receptors, GABA-B
  • Baclofen