Thalamic nuclei can generate intrathalamic rhythms similar to those observed at various arousal levels and pathophysiological conditions such as absence epilepsy. These rhythmic activities can be altered by a variety of neuromodulators that arise from brain stem regions as well as those that are intrinsic to the thalamic circuitry. Vasoactive intestinal peptide (VIP) is a neuropeptide localized within the thalamus and strongly attenuates intrathalamic rhythms via an unidentified receptor subtype. We have used transgenic mice lacking a specific VIP receptor, VPAC2, to identify its role in VIP-mediated actions in the thalamus. VIP strongly attenuated both the slow, 2-4 Hz and spindle-like 5-8 Hz rhythmic activities in slices from wild-type mice (VPAC2+/+) but not in slices from VPAC2 receptor knock-out mice (VPAC2-/-), which suggests a major role of VPAC2 receptors in the antioscillatory actions of VIP. Intracellular recordings revealed that VIP depolarized all relay neurons tested from VPAC2+/+ mice. In VPAC2-/- mice, however, VIP produced no membrane depolarization in 80% of neurons tested. In relay neurons from VPAC2+/+ mice, VIP enhanced the hyperpolarization-activated mixed cation current, Ih, via cyclic AMP activity, but VIP did not alter IH in VPAC2-/- mice. In VPAC2-/- mice, pituitary adenylate cyclase activating-polypeptide (PACAP) depolarized the majority of relay neurons via IH enhancement presumably via PAC1 receptor activation. Our findings suggest that VIP-mediated actions are predominantly mediated by VPAC2 receptors, but PAC1 receptors may play a minor role. The excitatory actions of VIP and PACAP suggest these peptides may not only regulate intrathalamic rhythmic activities, but also may influence information transfer through thalamocortical circuits.
|Number of pages||14|
|Journal||Journal of Neurophysiology|
|State||Published - 2006|
ASJC Scopus subject areas
- Neuroscience (all)