Electrophysiological complexity in the rat dorsomedial hypothalamus and its susceptibility to daily rhythms and high-fat diet

Eur J Neurosci. 2022 Aug;56(4):4363-4377. doi: 10.1111/ejn.15759. Epub 2022 Jul 18.

Abstract

The dorsomedial hypothalamus (DMH) in amongst the most important brain structures involved in the regulation of feeding behaviour and metabolism. In contrast to other hypothalamic centres, its main role is related to the circadian rhythmicity of food intake and energy homeostasis; both reported to be disrupted in obesity. In modern world, overweight and obesity reached global epidemic proportions. Thus, not only is it important to study their negative implications but also the mechanism responsible for their development. Here, we exposed rats to short-term (2-4 weeks) high-fat diet (HFD)-not long enough to induce obesity. Next, we performed electrophysiological patch-clamp recordings ex vivo from neurons in the DMH either during the day or at night. Our results showed a day-to-night change in the firing frequency of DMH cells, with higher activity during the dark phase. This was abolished by HFD consumption, resulting in a decreased threshold for action potential generation during the day and therefore increased electrical activity at this phase. We propose this electrophysiological disturbance as a mechanism for the induction of abnormal daytime feeding, previously observed for HFD-fed animals, which might in turn contribute to the development of obesity. In addition, we provide an electrophysiological characteristic of DMH neurons with a separation into three anatomically and functionally distinct subpopulations, namely, the compact part, separating the structure into the ventral and dorsal divisions. Our study is the first to show electrophysiological complexity of the DMH with its sensitivity to diet and daily rhythms.

Keywords: chronobiology; food intake; metabolism; obesity; patch-clamp.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Rhythm* / physiology
  • Diet, High-Fat* / adverse effects
  • Hypothalamus* / physiology
  • Obesity
  • Rats