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

Junmei Fan, Hongkui Zeng, David P. Olson, Kimberly M. Huber, Jay R. Gibson, Joseph S. Takahashi

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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 theSCNneurons expressing vasoactive intestinal peptide (VIP+neurons). Focusing on the local projection within the ventromedial SCN,wefound that VIP+afferents provided input onto49%of neurons with a preference for VIP-negative (VIP+) neurons. Responses were mediated byGABAA-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 presynapticVIP+neuronswereunchangedbetweendayandnight,andtheirnetworkconnectivityandsynaptic functionupthroughtheevoked 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 outputupthroughGABAA-R opening are invariant during the circadian cycle, but the effectonaction potential firing is modulated by postsynaptic processes occurring after GABAA-R channel opening.

Original languageEnglish (US)
Pages (from-to)1905-1920
Number of pages16
JournalJournal of Neuroscience
Volume35
Issue number5
DOIs
StatePublished - 2015

Keywords

  • Circadian
  • GABA
  • Network
  • SCN
  • Synapse
  • VIP

ASJC Scopus subject areas

  • General Neuroscience

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