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Nature. 2018 Mar 8;555(7695):204-209. doi: 10.1038/nature25488. Epub 2018 Feb 28.

Hierarchical neural architecture underlying thirst regulation.

Author information

1
Computation and Neural Systems, California Institute of Technology, Pasadena, California, USA.
2
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
3
Department of Physiology and Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, California, USA.
4
Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK.
5
Howard Hughes Medical Institute, Stanford University, Stanford, California, USA.
6
Department of Bioengineering, Stanford University, Stanford, California, USA.

Abstract

Neural circuits for appetites are regulated by both homeostatic perturbations and ingestive behaviour. However, the circuit organization that integrates these internal and external stimuli is unclear. Here we show in mice that excitatory neural populations in the lamina terminalis form a hierarchical circuit architecture to regulate thirst. Among them, nitric oxide synthase-expressing neurons in the median preoptic nucleus (MnPO) are essential for the integration of signals from the thirst-driving neurons of the subfornical organ (SFO). Conversely, a distinct inhibitory circuit, involving MnPO GABAergic neurons that express glucagon-like peptide 1 receptor (GLP1R), is activated immediately upon drinking and monosynaptically inhibits SFO thirst neurons. These responses are induced by the ingestion of fluids but not solids, and are time-locked to the onset and offset of drinking. Furthermore, loss-of-function manipulations of GLP1R-expressing MnPO neurons lead to a polydipsic, overdrinking phenotype. These neurons therefore facilitate rapid satiety of thirst by monitoring real-time fluid ingestion. Our study reveals dynamic thirst circuits that integrate the homeostatic-instinctive requirement for fluids and the consequent drinking behaviour to maintain internal water balance.

PMID:
29489747
PMCID:
PMC6086126
DOI:
10.1038/nature25488
[Indexed for MEDLINE]
Free PMC Article

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