title: Retrograde suppression of GABAergic currents in a subset of SCN neurons.
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.
authors.affiliation: Center for Research on Occupational and Environmental Toxicology and Department of Physiology and Pharmacology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Heinrich S
authors.initials: HS
authors.lastname: Gompf
authors.forename: Robert P
authors.initials: RP
authors.lastname: Irwin
authors.forename: Charles N
authors.initials: CN
authors.lastname: Allen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D004533:Egtazic Acid / Q000378:metabolism; D018755:GABA Agonists / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009118:Muscimol / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017440:Photoperiod; D051381:Rats; D017207:Rats, Sprague-Dawley; D013493:Suprachiasmatic Nucleus / Q000166:cytology*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D018755:GABA Agonists; D009118:Muscimol; D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; D002118:Calcium