Retrograde suppression of GABAergic currents in a subset of SCN neurons

Heinrich S. Gompf, Robert P. Irwin, Charles N. Allen

Research output: Contribution to journalArticle

5 Scopus citations

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 γ-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 GABAA 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.

Original languageEnglish (US)
Pages (from-to)3209-3216
Number of pages8
JournalEuropean Journal of Neuroscience
Volume23
Issue number12
DOIs
StatePublished - Jun 1 2006

Keywords

  • Calcium
  • Circadian rhythm
  • Dendrite
  • G-protein
  • Rat
  • Synaptic transmission

ASJC Scopus subject areas

  • Neuroscience(all)

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