DMV extrasynaptic NMDA receptors regulate caloric intake in rats

Area of Science:

• Neuroscience
• Physiology
• Metabolic Regulation

Background:

• Acute high-fat diet (aHFD) exposure causes transient hyperphagia, followed by restored caloric balance.
• This regulation involves synaptic N-methyl-D-aspartate (NMDA) receptors in the dorsal motor nucleus of the vagus (DMV), enhancing vagal control of gastric functions.

Purpose of the Study:

• To investigate the hypothesis that extrasynaptic NMDA receptor activation precedes and triggers synaptic NMDA receptor activation in DMV neurons.
• To elucidate the role of NMDA receptor subtypes in the regulation of gastric function and caloric intake following aHFD exposure.

Main Methods:

• Whole-cell patch-clamp recordings from gastric-projecting DMV neurons in Sprague-Dawley rats.
• In vivo recordings of gastric motility, tone, compliance, and emptying.
• Food intake studies assessing the effects of NMDA receptor antagonism.

Main Results:

• Inhibition of extrasynaptic NMDA receptors blocked aHFD-induced increases in glutamatergic transmission to DMV neurons and elevated gastric tone and motility.
• Chronic extrasynaptic NMDA receptor inhibition attenuated the regulation of caloric intake after aHFD exposure.
• Regulation of food intake post-aHFD involved synaptic NMDA receptor currents triggered by extrasynaptic NMDA receptor activation.

Conclusions:

• Extrasynaptic NMDA receptor activation is a critical upstream event initiating synaptic NMDA receptor-mediated responses in DMV neurons.
• These findings provide a mechanistic understanding of diet-induced hyperphagia and suggest potential therapeutic targets for obesity.