Neuroanatomical, electrophysiological, and morphological characterization of melanin-concentrating hormone cells coexpressing cocaine- and amphetamine-regulated transcript

Abstract

Melanin-concentrating hormone (MCH) cells in the hypothalamus regulate fundamental physiological functions like energy balance, sleep, and reproduction. This diversity may be ascribed to the neurochemical heterogeneity among MCH cells. One prominent subpopulation of MCH cells coexpresses cocaine- and amphetamine-regulated transcript (CART), and as MCH and CART can have opposing actions, MCH/CART+ and MCH/CART− cells may differentially modulate behavioural outcomes. However, it is not known if there are differences in cellular properties underlying their functional differences, thus we compared the neuroanatomical, electrophysiological, and morphological properties of MCH cells in male and femaleMch-cre;L10-Egfpreporter mice. Half of MCH cells expressed CART and were most prominent in the medial hypothalamus. Whole-cell patch-clamp recordings revealed differences in their passive and active membrane properties in a sex-dependent manner. Female MCH/CART+ cells had lower input resistances, but male cells largely differed in their firing properties. All MCH cells increased firing when stimulated, but their firing frequency decreases with sustained stimulation. MCH/CART+ cells showed stronger spike rate adaptation than MCH/CART− cells. The kinetics of excitatory events at MCH cells also differed by cell type, as the rising rate of excitatory events was slower at MCH/CART+ cells. By reconstructing the dendritic arborization of our recorded cells, we found no sex differences, but male MCH/CART+ cells had less dendritic length and fewer branch points. Overall, distinctions in topographical division and cellular properties between MCH cells add to their heterogeneity and help elucidate their response to stimuli or effect on modulating their respective neural networks.

Inhibitory actions of melanin‐concentrating hormone in the lateral septum

“…Baseline RMP was sampled from MCH-sensitive and MCH-insensitive cells in Clampfit immediately prior to MCH puff application. Input resistance, capacitance and rheobase were recorded and analysed as described in Miller et al (2024).…”

“…Neurons that produce melanin-concentrating hormone (MCH) are found primarily within the lateral hypothalamic area (LHA) (Beekly et al, 2020;Broberger, 1999;Broberger et al, 1998;Croizier et al, 2010;Miller et al, 2024), but they can send widespread projections throughout the brain (Bittencourt et al, 1992;Skofitsch et al, 1985). MCH neurons can express additional neuropeptides (Harthoorn et al, 2005;Mickelsen et al, 2017) and neurotransmitters like GABA (Jego et al, 2013) and glutamate (Chee et al, 2015).…”