The hypothalamus contains the highest diversity of neurons in the brain. Many of these neurons can co-release neurotransmitters and neuropeptides in a use-dependent manner. Investigators have hitherto relied on candidate protein-based tools to correlate behavioral, endocrine and gender traits with hypothalamic neuron identity. Here we map neuronal identities in the hypothalamus by single-cell RNA sequencing. We distinguished 62 neuronal subtypes producing glutamatergic, dopaminergic or GABAergic markers for synaptic neurotransmission and harboring the ability to engage in task-dependent neurotransmitter switching. We identified dopamine neurons that uniquely coexpress the Onecut3 and Nmur2 genes, and placed these in the periventricular nucleus with many synaptic afferents arising from neuromedin S neurons of the suprachiasmatic nucleus. These neuroendocrine dopamine cells may contribute to the dopaminergic inhibition of prolactin secretion diurnally, as their neuromedin S inputs originate from neurons expressing Per2 and Per3 and their tyrosine hydroxylase phosphorylation is regulated in a circadian fashion. Overall, our catalog of neuronal subclasses provides new understanding of hypothalamic organization and function.

Balance in the body's hormonal axes depends on feedback onto neuroendocrine hypothalamic neurons. This phenomenon involves transcriptional and biosynthetic effects, yet less is known about the potential rapid modulation of electrical properties. Here, we investigated this issue in the lactotrophic axis, in which the pituitary hormone prolactin is tonically inhibited by tuberoinfundibular dopamine (TIDA) neurons located in the hypothalamic arcuate nucleus. Whole-cell recordings were performed on slices of the rat hypothalamus. In the presence of prolactin, spontaneously oscillating TIDA cells depolarized, switched from phasic to tonic discharge, and exhibited broadened action potentials. The underlying prolactin-induced current is composed of separate low-and high-voltage components that include the activation of a transient receptor potential-like current and the inhibition of a Ca 2ϩ -dependent BK-type K ϩ current, respectively, as revealed by ion substitution experiments and pharmacological manipulation. The two components of the prolactin-induced current appear to be mediated through distinct signaling pathways as the high-voltage component is abolished by the phosphoinositide 3-kinase blocker wortmannin, whereas the low-voltage component is not. This first description of the central electrophysiological actions of prolactin suggests a novel feedback mechanism. By simultaneously enhancing the discharge and spike duration of TIDA cells, increased serum prolactin can promote dopamine release to limit its own secretion with implications for the control of lactation, sexual libido, fertility, and body weight.

Electrical junctions are widespread within the mammalian CNS. Yet, their role in organizing neuronal ensemble activity remains incompletely understood. Here, in a functionally well-characterized system – neuroendocrine tuberoinfundibular dopamine (TIDA) neurons - we demonstrate a striking species difference in network behavior: rat TIDA cells discharge in highly stereotyped, robust, synchronized slow oscillations, whereas mouse oscillations are faster, flexible and show substantial cell-to-cell variability. We show that these distinct operational modes are explained by the presence of strong TIDA-TIDA gap junction coupling in the rat, and its complete absence in the mouse. Both species, however, encompass a similar heterogeneous range of intrinsic resonance frequencies, suggesting similar network building blocks. We demonstrate that gap junctions select and impose the slow network rhythm. These data identify a role for electrical junctions in determining oscillation frequency and show how related species can rely on distinct network strategies to accomplish adaptive control of hormone release.

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This qualitative review on rotavirus infection and its complications in the central nervous system (CNS) aims to understand the gut–brain mechanisms that give rise to CNS driven symptoms such as vomiting, fever, feelings of sickness, convulsions, encephalitis, and encephalopathy. There is substantial evidence to indicate the involvement of the gut–brain axis in symptoms such as vomiting and diarrhea. The underlying mechanisms are, however, not rotavirus specific, they represent evolutionarily conserved survival mechanisms for protection against pathogen entry and invasion. The reviewed studies show that rotavirus can exert effects on the CNS trough nervous gut–brain communication, via the release of mediators, such as the rotavirus enterotoxin NSP4, which stimulates neighboring enterochromaffin cells in the intestine to release serotonin and activate both enteric neurons and vagal afferents to the brain. Another route to CNS effects is presented through systemic spread via lymphatic pathways, and there are indications that rotavirus RNA can, in some cases where the blood brain barrier is weakened, enter the brain and have direct CNS effects. CNS effects can also be induced indirectly as a consequence of systemic elevation of toxins, cytokines, and/or other messenger molecules. Nevertheless, there is still no definitive or consistent evidence for the underlying mechanisms of rotavirus-induced CNS complications and more in-depth studies are required in the future.