High‐Fat Diet Induced Modulation of Glutamatergic Currents in Neurons of the Dorsal Motor Nucleus of the Vagus

A high fat diet (HFD) has been shown to induce reactive gliosis in many areas of the central nervous system, including the brainstem. This gliosis, and particularly astrocyte activation, have been shown to modulate the properties of the synapse including synaptic strength. While we demonstrated previously that longer‐term exposure to a HFD affects synaptic transmission to neurons of the dorsal motor nucleus of the vagus (DMV) in rats, the effects of short‐term exposure have not been examined. The purpose of this study is to test the hypothesis that, following short periods of exposure to a HFD, astrocyte activation contributes to the modulation of synaptic transmission in the DMV. Whole cell patch clamp recordings of DMV neurons were made from thin (300mm) brainstem slices from Sprague‐Dawley rats 4–6 years of age. Rats were fed a control diet (14% kcal from fat) throughout the study, or a HFD (60% kcal from fat) for 3–7 days prior to experimentation. The effects of fluoroacetate (100μM), an astrocyte metabolism inhibitor, on glutamatergic miniature excitatory postsynaptic currents (mEPSCs) were examined. The short periods of exposure to HFD employed in the current study did not alter DMV neuronal properties. Since astrocytes are primarily responsible for glutamate uptake and clearance from the synapse, neurons were defined as responding to fluoroacetate if the drug induced a significant increase in mEPSC decay time. Accordingly, 7/13 HFD neurons responded to fluoroacetate, and in these neurons, both the amplitude and frequency of glutamatergic mEPSCs were decreased significantly (11.7 ± 0.85 pA in fluoroacetate vs 15.2 ± 0.85 pA in control; 0.5±0.09 vs 1.1±0.25 events per second; n=7; p<0.05 for both). In contrast, in control rats, neither the amplitude nor frequency of mEPSCs were affected by fluoroacetate, even in the 3/12 responding neurons (16.5 ± 0.55 pA vs 15.0 ± 0.1 pA; 0.8±0.25 vs 1.0±0.34 events per second; n=6; p>0.05 for both). This study suggests that even short periods of exposure to a HFD alter astrocyte activity that subsequently modulates synaptic transmission. Fluoroacetate‐induced alterations in both frequency and amplitude of glutamatergic synaptic events suggests that this modulation occurs both presynaptically and postsynaptically. Astrocytes are known to release glycine and D‐serine, which are essential co‐factors for the NMDA receptor. While the NMDA receptor appears not to be tonically active in the DMV under normal conditions, altered astrocyte function may contribute to the increase in glutamatergic mEPSC amplitude in HFD. In total, these results indicate that short‐term exposure to a high fat diet may alter the synaptic strength in the DMV, even in the absence of HFD‐induced weight gain or peripheral inflammation. These modulations of vagal circuitry may dysregulate gastrointestinal reflexes or disrupt gastric motility. Support or Funding Information Funded by NIH 078364 and NSF IOS1148978