title: Excitatory actions of vasoactive intestinal peptide on mouse thalamocortical neurons are mediated by VPAC2 receptors.
abstract: 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, VPAC(2), 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 (VPAC(2)(+/+)) but not in slices from VPAC(2) receptor knock-out mice (VPAC(2)(-/-)), which suggests a major role of VPAC(2) receptors in the antioscillatory actions of VIP. Intracellular recordings revealed that VIP depolarized all relay neurons tested from VPAC(2)(+/+) mice. In VPAC(2)(-/-) mice, however, VIP produced no membrane depolarization in 80% of neurons tested. In relay neurons from VPAC(2)+/+ mice, VIP enhanced the hyperpolarization-activated mixed cation current, I(h), via cyclic AMP activity, but VIP did not alter I(h) in VPAC(2)-/- mice. In VPAC(2)-/- mice, pituitary adenylate cyclase activating-polypeptide (PACAP) depolarized the majority of relay neurons via I(h) enhancement presumably via PAC(1) receptor activation. Our findings suggest that VIP-mediated actions are predominantly mediated by VPAC(2) receptors, but PAC(1) 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.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois, Urbana, IL 61801, USA.
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Charles L
authors.initials: CL
authors.lastname: Cox
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects*; D000242:Cyclic AMP / Q000502:physiology; D004594:Electrophysiology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000187:drug effects / Q000235:genetics; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000187:drug effects* / Q000235:genetics; D015290:Second Messenger Systems / Q000502:physiology; D013788:Thalamus / Q000166:cytology* / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP