title: Vasoactive intestinal polypeptide (VIP)-expressing neurons in the suprachiasmatic nucleus provide sparse GABAergic outputs to local neurons with circadian regulation occurring distal to the opening of postsynaptic GABAA ionotropic receptors.
abstract: GABAergic synaptic transmission plays an important role in resetting and synchronizing circadian rhythms in the suprachiasmatic nucleus (SCN). Although the circadian modulation of intrinsic membrane currents and biochemical signaling have been examined in the SCN, the modulation of specific synaptic pathways within the SCN is unexplored. In addition, little is known about the functional properties of these pathways, including which ones involve GABAA receptors (GABAA-Rs). In brain slices obtained from mice, we examined synaptic responses originating from the SCN neurons expressing vasoactive intestinal peptide (VIP+ neurons). Focusing on the local projection within the ventromedial SCN, we found that VIP+ afferents provided input onto 49% of neurons with a preference for VIP-negative (VIP-) neurons. Responses were mediated by GABAA-Rs. The projection was sparsely connected and preferentially targeted a subset of SCN neurons unrelated to postsynaptic VIP expression. For most aspects of VIP+ network output, there was no circadian regulation. Excitability and spontaneous firing of the presynaptic VIP+ neurons were unchanged between day and night, and their network connectivity and synaptic function up through the evoked synaptic conductance were also unchanged. On the other hand, VIP+ input onto VIP- neurons became less inhibitory at night suggesting a postsynaptic alteration in the coupling of GABAA-R conductances to action potential firing. These data suggest that components of the VIP network and its synaptic output up through GABAA-R opening are invariant during the circadian cycle, but the effect on action potential firing is modulated by postsynaptic processes occurring after GABAA-R channel opening.
authors: Department of Neuroscience and.
authors: Junmei
authors: J
authors: Fan
authors: Allen Institute for Brain Science, Seattle, Washington, 98103, and.
authors: Hongkui
authors: H
authors: Zeng
authors: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109.
authors: David P
authors: DP
authors: Olson
authors: Department of Neuroscience and.
authors: Kimberly M
authors: KM
authors: Huber
authors: Department of Neuroscience and Jay.Gibson@UTSouthwestern.edu Joseph.Takahashi@UTSouthwestern.edu.
authors: Jay R
authors: JR
authors: Gibson
authors: Department of Neuroscience and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, Jay.Gibson@UTSouthwestern.edu Joseph.Takahashi@UTSouthwestern.edu.
authors: Joseph S
authors: http://orcid.org/0000-0003-0384-8878
authors: JS
authors: Takahashi
mesh_terms: D000200:Action Potentials; D000818:Animals; D002940:Circadian Rhythm; D005260:Female; D059330:GABAergic Neurons / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D009475:Neurons, Afferent / Q000378:metabolism* / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D013569:Synapses / Q000378:metabolism / Q000502:physiology; D055366:Synaptic Potentials; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D011963:Receptors, GABA-A; D014660:Vasoactive Intestinal Peptide; D005680:gamma-Aminobutyric Acid
keywords: GABA; SCN; VIP; circadian; network; synapse
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