Vasoactive intestinal peptide selectively depolarizes thalamic relay neurons and attenuates intrathalamic rhythmic activity.

Abstract

The reciprocal synaptic relationship between the relay thalamus and surrounding thalamic reticular nucleus can lead to the generation of various rhythmic activities that are associated with different levels of behavioral states as well as certain pathophysiological conditions. Intrathalamic rhythmic activities may be attenuated by numerous neuromodulators that arise from a variety of brain stem nuclei. This study focuses on the potential role of a particular neuropeptide, vasoactive intestinal peptide (VIP). VIP and its receptors are localized within the thalamic circuit and thus may serve as an endogenous modulator of the rhythmic activity. Using extracellular multiple-unit recording techniques, we found that VIP strongly attenuated the slow, 2- to 4-Hz intrathalamic rhythm. This rhythm is similar to that observed during slow wave sleep and certain pathophysiological conditions such as generalized absence epilepsy. Using intracellular recording techniques, we found that VIP selectively depolarized relay neurons in the ventrobasal nucleus but had negligible actions on neurons in thalamic reticular nucleus. The VIP-mediated depolarization is produced via an enhancement of the nonselective cation conductance, Ih. The antioscillatory actions of VIP likely occur by shifting the membrane potential to decrease the probability of burst discharge by relay neurons, a requirement to maintain the rhythmic activity. Not only does VIP alter the intrathalamic rhythmic activity, this peptide that is endogenous to the thalamic circuit may also play a significant role in the regulation of information transfer through the thalamocortical circuit.