Endothelin-1 modulates hippocampal and hypothalamic neuronal network activity in mouse primary dissociated cultures and brain slices

May 28, 2026Peptides

Endothelin-1 changes nerve cell activity in mouse memory and hormone control brain areas

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Endothelin-1 (ET-1) significantly decreased firing frequency in hippocampal neurons while increasing it in histaminergic neurons of the caudal hypothalamus.

ET-1 is associated with reduced neuronal firing frequency in hippocampal pyramidal neurons.
In contrast, ET-1 increases firing frequency and synchrony in histaminergic neurons located in the tuberomammillary nucleus.
Higher expression of ET receptors is observed in the caudal hypothalamus compared to the hippocampus.
ET-1 induces a delayed increase in firing frequency of histaminergic neurons and a decrease in dentate gyrus granule cells.
The differential effects of ET-1 suggest its role in modulating neuronal excitability and network activity related to arousal.

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Endothelin-1 (ET-1) is known not only as a vasoconstrictor, but also as a neuromodulator. It can reset the circadian clock and we hypothesized that it modulates neuronal excitability and network activity in histaminergic neurons (HN). HN, located in the tuberomammillary nucleus (TMN) of the caudal hypothalamus (cHPT), fire spontaneously during waking and promote arousal. Previous studies have shown that ET-1 reduces firing frequency of hippocampal pyramidal neurons, whereas its effects on electrophysiological properties of HN remain unknown. We now studied the expression of ET-receptors (ETand ET) in the hippocampus (HPC) and caudal hypothalamus by single-cell RT-PCR and qPCR. The responses to ET-1 were studied in HN and dentate gyrus granule cells (DGgc) of brain slices using patch-clamp recordings and primary cultures of cHPT and HPC using Microelectrode Arrays (MEAs). ET-1 significantly decreased firing frequency in HPC and increased it in cHPT cultures with prevailing inhibition of individual MEA channels in HPC and excitation in cHPT. Neuronal synchrony and bursting were significantly increased in cHPT. Relative to HPC, cHPT displayed higher expression of ET. In brain slices, ET-1 induced a delayed bosentan-sensitive increase in HN and decrease in DGgc firing frequency. HN expressed ET(15 of 22 HN) and ET(4 of 15 ETpositive HN), whereas only ETwas expressed in 50% of DGgc. We conclude that ET-1 differentially modulates cHPT and HPC. By exciting HN and synchronizing neuronal network activity in cHPT, ET-1 may contribute to cellular and circuit-level mechanisms in the regulation of arousal and wakefulness. A B B B A B B

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Endothelin-1 modulates hippocampal and hypothalamic neuronal network activity in mouse primary dissociated cultures and brain slices

Abstract

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