A synaptoid connectome differentiates tanycytic subpopulations and underlies neuroglial communication and neuroendocrine regulation

Abstract

Abstract Tanycytes are radial-glia-like cells that play important roles in regulating the neuroendocrine system and metabolism. Synapse-like (synaptoid) connections have previously been described between neurons and tanycytes, but their structure and function are unclear. Here, we report that neuron-tanycyte synaptoids are abundant and resemble typical neuronal synapses in shape and composition. Tanycytic subtypes receive specific inputs from a variety of hypothalamic as well as extrahypothalamic neuronal populations and respond to several neurotransmitters and neuromodulators. As proof-of-principle of their functional relevance, we demonstrate in mice, that two distinct populations of kisspeptin neurons, which stimulate the gonadotropic axis, innervate different tanycytic subsets of the mediobasal hypothalamus to control basal levels of the gonadotropin luteinizing hormone (LH) and its pulsatile release pattern, in a sex‑ and region‑specific manner. Neuron-tanycyte synaptoid connections are thus widespread, diverse and functionally specific elements of hypothalamic neural circuits that play a key role in finetuning hormonal axes.