Modulation of Voltage-Gated Calcium Channels by Group II Metabotropic Glutamate Receptors in the Paraventricular Nucleus of the Thalamus

Abstract

Compounds that interact with Group II metabotropic glutamate receptors (mGluRs) have antipsychotic effects in animal models. These drugs have also shown efficacy in the treatment of schizophrenia in humans. The mechanism of action is believed to arise from a reduction of glutamatergic transmission in limbic and forebrain regions commonly associated with this disorder. Previous anatomical tracer and lesion studies have revealed that neurons of the paraventricular nucleus of the thalamus (PVT) are an important source of the glutamatergic drive to these specific regions. However, the function of Group II mGluRs in the PVT remains to be determined. Whole-cell recordings from PVT neurons reveal that activation of these receptors has two interesting effects; it reduces calcium entry through voltage-gated calcium channels and it causes neurons to hyperpolarize. These two effects may contribute to affect the excitability of PVT neurons, an action that may underlie the effectiveness of Group II mGluR-activating compounds.