Hindbrain glutamatergic control of meal size: Evidence for participation of specific N-methyl- D-aspartate receptor (NMDAR) phenotypes on myelinated vagal afferent neurons.

Abstract

Previously published results from our laboratory indicate that injection of NMDA receptor antagonists into the dorsal hindbrain increase food intake and suggest that capsaicin-resistant (myelinated) vagal afferents terminals that express NMDA-type glutamate receptors participate in control of meal size. NMDA receptors are heteromeric ion channels incorporating distinct subunits, including NR1, NR2A, NR2B, NR2C and NR2D. The NMDA channel's electrical and signaling properties are determined by its NR2 subunit phenotype. In the present study we tested the hypothesis that myelinated vagal afferent neurons express different NMDAR NR2 subunits than non-myelinated neurons. Six-week-old male Sprague-Dawley rats received intraperitoneal injections of capsaicin or vehicle. Nodose ganglia were processed for with primary antibodies against the capsaicin receptor (VR1), and NR1, NR2B, NR2C, or NR2D NMDAR subunits. In vehicle-treated rats, at least 60% of all nodose vagal afferents were immunopositive for VR-1 and capsaicin treatment reduced VR1 immunoreactivity to 10%. Furthermore, capsaicin reduced the number of NMDA NR1 and NR2B subunit expressing neurons by at least 50%, while resulting in no detectable loss of NMDA NR2C or NR2D immunopositive neurons. Our results indicate that NMDA NR2C and NR2D subunit immunoreactivity in the nodose ganglia is limited to capsaicin-resistant myelinated vagal afferents. Taken collectively with previous behavioral findings, we hypothesize that NMDA NR2C and/or NR2D expressing vagal afferents may mediate increased food intake evoked by injection of NMDA antagonists into the hindbrain and may contribute to the control of meal size. Supported by NIH Grants DK52849 and NS20561 and Poncin Scholarship 2006.