Nesfatin‐1 Alters Synaptic Activity in Neurons in the Nucleus of the Solitary Tract

Abstract

Nesfatin‐1 (nes‐1) is a recently discovered neuropeptide that decreases food intake and is expressed in the medullary nucleus of the solitary tract (NTS). In order to begin elucidating the mechanisms of nes‐1 actions, we studied the effect of nes‐1 on synaptic activity in NTS neurons using whole‐cell voltage clamp recordings. Bath applied nes‐1 (10nM) did not influence the frequency (freq, 157±49 vs 163±48 events/100s, p=0.85) nor amplitude (amp, 29±4 vs 51±13 pA, p=0.11) of EPSCs recorded from rat medial NTS neurons (n=8) in slice. Nes‐1 did, however, induce an increase in freq (144±45 vs 224±53 events/100s, p=0.03) and amp (57±9 vs 74±12 pA, p=0.02) of IPSCs in 8/9 cells. We next used tetrodotoxin to study spontaneous miniature EPSCs and IPSCs. 10nM nes‐1 did not affect freq (305±68 vs 275±45 events/100s, p=0.37) nor amp (30±2 vs 34±4 pA, p=0.25) of mEPSCs (n=7). Neither the freq (335±102 vs 385±90 events/100s, p=0.41) nor amp (85±12 vs 92±12 pA, p=0.31) of mIPSCs was affected (n=9) by nes‐1. Our findings identify NTS as a site where nes‐1 acts to selectively enhance GABAergic tone and increase inhibitory synaptic events to potentially modify food intake.Research support: NSERC, FQRNT, CIHR.