A developmental switch between electrical and neuropeptide communication in the ventromedial hypothalamus

Dissecting neural connectivity patterns within local brain regions is an essential step to understanding the function of the brain.¹ Neural microcircuits in brain regions, such as the neocortex and the hippocampus, have been extensively studied.² By contrast, the microcircuit in the hypothalamus remains largely uncharacterized. The hypothalamus is crucial for animals' survival and reproduction.³ Knowledge of how different hypothalamic nuclei coordinate with each other and outside brain regions for hypothalamus-related functions has been significantly advanced.^4-9 Although there are limited studies on the neural microcircuit in the lateral hypothalamus (LHA)^10,11 and the suprachiasmatic nucleus (SCN),^12,13 the patterns of neural microcircuits in most of the given hypothalamic nuclei remain largely unknown. This study applied combinatory approaches to address the local neural circuit pattern in the ventromedial hypothalamus (VMH) and other hypothalamic nuclei. We discovered a unique neural circuit design in the VMH. Neurons in the VMH were electrically coupled at the early postnatal stage like ones in the neocortex.¹⁴ However, unlike neocortical neurons,^14,15 they developed very few chemical synapses after the disappearance of electrical synapses. Instead, VMH neurons communicated with neuropeptides. The similar scarceness of synaptic connectivity found in other hypothalamic nuclei further indicated that the lack of synaptic connections is a unique feature for local neural circuits in most adult hypothalamic nuclei. Thus, our findings provide a solid synaptic basis at the cellular level to understand hypothalamic functions better.