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 GABAAIonotropic Receptors

Feb 6, 2015The Journal of neuroscience : the official journal of the Society for Neuroscience

VIP-producing neurons in the brain's clock area send limited inhibitory signals that affect timing after receptor activation

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Abstract

VIP+ neurons provide input to 49% of VIP-negative neurons in the SCN.

GABAergic synaptic transmission is implicated in circadian rhythm modulation in the suprachiasmatic nucleus (SCN).
VIP+ afferents primarily target VIP-negative neurons, indicating a selective synaptic connection.
Responses from these connections are mediated by GABAA receptors.
For most aspects of VIP+ network output, there is no circadian regulation observed.
Excitability and spontaneous firing rates of VIP+ neurons do not change between day and night.
VIP+ input onto VIP- neurons becomes less inhibitory at night, suggesting changes in postsynaptic responses.

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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.

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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 GABAAIonotropic Receptors

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