Excitatory actions of vasoactive intestinal peptide on mouse thalamocortical neurons are mediated by VPAC2 receptors.
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.
Lee
Sang-Hun
SH
Department of Molecular and Integrative Physiology, University of Illinois, Urbana, IL 61801, USA.
Cox
Charles L
CL
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*
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