Excitatory actions of vasoactive intestinal peptide on mouse thalamocortical neurons are mediated by VPAC2 receptors

Sang Hun Lee, Charles L. Cox

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish
Pages (from-to)858-871
Number of pages14
JournalJournal of Neurophysiology
Issue number2
StatePublished - 2006

ASJC Scopus subject areas

  • Neuroscience (all)
  • Physiology


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