PRESYNAPTIC IONOTROPIC GLUTAMATE RECEPTORS MODULATE GABA RELEASE IN THE MOUSE DORSAL MOTOR NUCLEUS OF THE VAGUS

Regulation of GABA release in the dorsal motor nucleus of the vagus (DMV) potently influences vagal output to the viscera. The presence of functional ionotropic glutamate receptors (iGluRs) on GABAergic terminals that rapidly alter GABA release onto DMV motor neurons has been suggested previously, but the receptor subtypes contributing to the response are unknown. We examined the effect of selective activation and inhibition of iGluRs on tetrodotoxin-insensitive, miniature inhibitory postsynaptic currents (mIPSCs) in DMV neurons using patch-clamp recordings in brainstem slices from mice. Capsaicin, which activates transient receptor potential vanilloid type 1 (TRPV1) receptors and increases mIPSC frequency in the DMV via an iGluR-mediated, heterosynaptic mechanism, was also applied to assess GABA release subsequent to capsaicin-stimulated glutamate release. Application of glutamate, N-methyl-D-aspartate (NMDA), or kainic acid (KA), but not AMPA, resulted in increased mIPSC frequency in most neurons. Inhibition of AMPA/KA receptors reduced mIPSC frequency, but selective antagonism of AMPA receptors did not alter GABA release, implicating the presence of presynaptic KA receptors on GABAergic terminals. Whereas NMDA application increased mIPSC frequency, blocking NMDA receptors was without effect, indicating that presynaptic NMDA receptors were present, but not activated by ambient glutamate levels in the slice. The effect of NMDA was prevented by AMPA/KA receptor blockade, suggesting indirect involvement of NMDA receptors. The stimulatory effect of capsaicin on GABA release was prevented when AMPA/KA or NMDA, but not AMPA receptors were blocked. Results of these studies indicate that presynaptic NMDAR and KA receptors regulate GABA release in the DMV, representing a heterosynaptic arrangement for rapidly modulating parasympathetic output, especially when synaptic excitation is elevated. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.