N‐methyl D‐aspartate (NMDA) receptors endow dendrites of gonadotropin releasing‐hormone (GnRH) neurons with additional active properties

Abstract

Dendrites of GnRH neurons express tetrodotoxin‐sensitive voltage‐gated sodium channels and generate action potentials. Other dendrites exhibiting action potentials possess additional active properties such as NMDA‐mediated potentials. We tested the hypothesis that GnRH dendrites express R1 subunits of NMDA receptors and exhibit amplification of sub‐threshold, excitatory post‐synaptic potentials (EPSPs) via NMDA receptor activation. Immunochemistry indicated GnRH dendrites express R1 subunits. Stimulating living GnRH dendrites with simulated sub‐threshold EPSPs resulted in plateau potentials and individual action potentials. When GABAergic inputs were blocked with picrotoxin (100 μM), repetitive action potentials occurred. The NMDA receptor antagonist D‐2‐amino‐5‐phosphono‐valeric (50 μM) eliminated responses. In small diameter dendrites, NMDA receptors would have a pronounced impact. Activating simulated NMDA conductances (at 560 μm dendrite length) in our compartmental models of GnRH neurons resulted in repetitive action potentials. Activating proximal NMDA receptors (at 200 and 100 μm dendrite length) diminished the impact of NMDA receptors. Our findings indicate GnRH dendrites exhibit regionalized expression of the NMDA conductance thereby forming location‐dependent microdomains where estrogen‐sensitive GABAergic neurons can regulate local excitability.