Thirst-associated preoptic neurons encode an aversive motivational drive

Allen, William E.; DeNardo, Laura A; Chen, Michael Z.; Liu, CD; Loh, Kyle M.; Fenno, Lief E.; Ramakrishnan, Charu; Deisseroth, Karl; Luo, Liqun

doi:10.1126/science.aan6747

Cited by 272 publications

(272 citation statements)

References 51 publications

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“…In our analysis, MnPO nNOS neurons project to various areas including the hypothalamus and the midbrain (Extended Data Fig. 9a; see also ref. 18).…”

Section: Discussionmentioning

confidence: 91%

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Hierarchical neural architecture underlying thirst regulation

Augustine

Gökçe

Lee

et al. 2018

Nature

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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.

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“…In our analysis, MnPO nNOS neurons project to various areas including the hypothalamus and the midbrain (Extended Data Fig. 9a; see also ref. 18).…”

Section: Discussionmentioning

confidence: 91%

“…It has been shown that water intake rapidly suppresses the activity of thirst neurons in the lamina terminalis 10,18 (Extended Data Fig. 4).…”

Section: Mnpoglp1r → Sfonnos Inhibitory Inputmentioning

confidence: 94%

Hierarchical neural architecture underlying thirst regulation

Augustine

Gökçe

Lee

et al. 2018

Nature

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121

139

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“…The activity of glutamatergic hypothalamic thirst-related neurons establishes a persistent, aversive motivational drive that animals can reduce in real time by consuming water (19, 20). The brainwide activity mode we identify appears to represent the direct effects of this thirst neuron activity that is broadcast to downstream circuits.…”

Section: Discussionmentioning

confidence: 99%

Thirst regulates motivated behavior through modulation of brainwide neural population dynamics

Allen

Chen

Pichamoorthy

et al. 2019

Science

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Neuron activity across the brain How is it that groups of neurons dispersed through the brain interact to generate complex behaviors? Three papers in this issue present brain-scale studies of neuronal activity and dynamics (see the Perspective by Huk and Hart). Allen et al. found that in thirsty mice, there is widespread neural activity related to stimuli that elicit licking and drinking. Individual neurons encoded task-specific responses, but every brain area contained neurons with different types of response. Optogenetic stimulation of thirst-sensing neurons in one area of the brain reinstated drinking and neuronal activity across the brain that previously signaled thirst. Gründemann et al. investigated the activity of mouse basal amygdala neurons in relation to behavior during different tasks. Two ensembles of neurons showed orthogonal activity during exploratory and nonexploratory behaviors, possibly reflecting different levels of anxiety experienced in these areas. Stringer et al. analyzed spontaneous neuronal firing, finding that neurons in the primary visual cortex encoded both visual information and motor activity related to facial movements. The variability of neuronal responses to visual stimuli in the primary visual area is mainly related to arousal and reflects the encoding of latent behavioral states. Science , this issue p. eaav3932 , p. eaav8736 , p. eaav7893 ; see also p. 236

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“…27,28 Although ablation of the subfornical organ did not impair drinking responses to systemic infusion of hypertonic saline in rats and sheep, 7,29 if it was ablated together with the OVLT in sheep, drinking to this stimulus was impaired compared to animals in which the OVLT alone was ablated. [36][37][38][39] Furthermore, recent experiments in mice show that optogenetic stimulation of osmoresponsive neurones in the subfornical organ or OVLT (as indicated by their expression of c-Fos in response to hypertonicity or dehydration), immediately begin to drink water. These neurones express several genes that include neuronal nitric oxide synthase (nNOS), Ca/calmodulin-dependent protein kinase II, the transcription factor ETS translocation variant-1 and the angiotensin AT 1a receptor.…”

Section: Osmoregulatory Thirstmentioning

confidence: 99%

From sensory circumventricular organs to cerebral cortex: Neural pathways controlling thirst and hunger

McKinley

Denton

Ryan

et al. 2019

J Neuroendocrinology

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Much progress has been made during the past 30 years with respect to elucidating the neural and endocrine pathways by which bodily needs for water and energy are brought to conscious awareness through the generation of thirst and hunger. One way that circulating hormones influence thirst and hunger is by acting on neurones within sensory circumventricular organs (CVOs). This is possible because the subfornical organ and organum vasculosum of the lamina terminalis (OVLT), the sensory CVOs in the forebrain, and the area postrema in the hindbrain lack a normal blood‐brain barrier such that neurones within them are exposed to blood‐borne agents. The neural signals generated by hormonal action in these sensory CVOs are relayed to several sites in the cerebral cortex to stimulate or inhibit thirst or hunger. The subfornical organ and OVLT respond to circulating angiotensin II, relaxin and hypertonicity to drive thirst‐related neural pathways, whereas circulating amylin, leptin and possibly glucagon‐like peptide‐1 act at the area postrema to influence neural pathways inhibiting food intake. As a result of investigations using functional brain imaging techniques, the insula and anterior cingulate cortex, as well as several other cortical sites, have been implicated in the conscious perception of thirst and hunger in humans. Viral tracing techniques show that the anterior cingulate cortex and insula receive neural inputs from thirst‐related neurones in the subfornical organ and OVLT, with hunger‐related neurones in the area postrema having polysynaptic efferent connections to these cortical regions. For thirst, initially, the median preoptic nucleus and, subsequently, the thalamic paraventricular nucleus and lateral hypothalamus have been identified as likely sites of synaptic links in pathways from the subfornical organ and OVLT to the cortex. The challenge remains to identify the links in the neural pathways that relay signals originating in sensory CVOs to cortical sites subserving either thirst or hunger.

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Thirst-associated preoptic neurons encode an aversive motivational drive

Cited by 272 publications

References 51 publications

Hierarchical neural architecture underlying thirst regulation

Hierarchical neural architecture underlying thirst regulation

Thirst regulates motivated behavior through modulation of brainwide neural population dynamics

From sensory circumventricular organs to cerebral cortex: Neural pathways controlling thirst and hunger

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