NMDA receptor - mediated modulation of excitatory 1

28 29 Activity of neurons in the dorsal motor nucleus of the vagus nerve (DMV) is 30 closely regulated by synaptic input, and regulation of that input by glutamate receptors 31 on presynaptic terminals has been proposed. Presynaptic NMDA receptors have been 32 identified in a number of brain regions and act to modulate neurotransmitter release, but 33 functional presynaptic NMDA receptors have not been adequately studied in the DMV. 34 This study identified the presence and physiological function of presynaptic NMDA 35 receptors on synaptic input to DMV neurons. Whole-cell patch-clamp recordings from 36 DMV neurons in acute slices from mice revealed prevalent miniature excitatory 37 postsynaptic currents (mEPSCs), which were significantly increased in frequency, but 38 not amplitude, by application of NMDA. Antagonism of NMDA receptors with DL-239 Amino-5phosphonopentanoic acid (AP-5; 100 μM) resulted in a decrease in mEPSC 40 frequency and an increase in the paired pulse ratio of responses following afferent 41 stimulation. No consistent effects of presynaptic NMDA receptor modulation were 42 observed on GABAergic inputs. These results suggest that presynaptic NMDA 43 receptors are present in the DVC and function to facilitate the release of glutamate 44 preferentially onto DMV neurons tonically, with little effect on GABA release. This type 45 of presynaptic modulation represents a potentially novel form of glutamate regulation in 46 the DMV, which may function to regulate glutamate-induced activity of central 47 parasympathetic circuits. 48 49