Retrograde suppression of GABAergic currents in a subset of SCN neurons

Eur J Neurosci. 2006 Jun;23(12):3209-16. doi: 10.1111/j.1460-9568.2006.04850.x.

Abstract

Many postsynaptic neurons release a retrograde transmitter that modulates presynaptic neurotransmitter release. In the suprachiasmatic nucleus (SCN), retrograde signaling is suggested by the presence of dendritic dense-core vesicles. Whole-cell voltage-clamp recordings were made from rat SCN neurons to determine whether a retrograde messenger could modulate the activity of afferent gamma-aminobutyric acid (GABA)ergic inputs. The frequency and amplitude of spontaneous GABAergic currents was significantly reduced in a subpopulation of SCN neurons (eight out of 13) following a postsynaptic depolarization. Similarly, a postsynaptic depolarization significantly reduced the amplitude of evoked GABAergic currents during both day and night recordings. A postsynaptic depolarizing pulse eliminated paired-pulse inhibition of GABAergic currents consistent with a presynaptic mechanism. Muscimol-activated currents were not altered by postsynaptic depolarization, demonstrating that the activity of GABA(A) receptors was not altered. Depolarization-induced inhibition of the GABAergic currents was not observed when a Ca2+ chelator was included in the microelectrode. Postsynaptic depolarization significantly increased the Ca2+ concentration in both the soma and dendrites. The dendritic Ca2+ levels increased faster, to a higher concentration and decayed faster than in the soma. The depolarization-induced inhibition of the evoked GABAergic current was blocked by the G-protein uncoupling agent N-ethylmaleimide, suggesting that the retrograde messenger acts on a pertussis toxin-sensitive G-protein-coupled receptor. Because the majority of SCN neurons receive GABAergic input from neighboring cells, these results describe a retrograde signaling mechanism by which SCN neurons can modulate GABAergic synaptic input.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism
  • Chelating Agents / metabolism
  • Circadian Rhythm / physiology
  • Egtazic Acid / metabolism
  • GABA Agonists / metabolism
  • Male
  • Membrane Potentials / physiology
  • Muscimol / metabolism
  • Neurons / cytology
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Photoperiod
  • Rats
  • Rats, Sprague-Dawley
  • Suprachiasmatic Nucleus / cytology*
  • Synapses / physiology
  • Synaptic Transmission / physiology*
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Chelating Agents
  • GABA Agonists
  • Muscimol
  • Egtazic Acid
  • gamma-Aminobutyric Acid
  • Calcium