Thirst recruits phasic dopamine signaling through subfornical organ neurons

Abstract

Thirst is a highly potent drive that motivates organisms to seek out and consume balance-restoring stimuli. The detection of dehydration is well understood and involves signals of peripheral origin and the sampling of internal milieu by first order homeostatic neurons within the lamina terminalis—particularly glutamatergic neurons of the subfornical organ expressing CaMKIIa (SFOCaMKIIa). However, it remains unknown whether mesolimbic dopamine pathways that are critical for motivation and reinforcement integrate information from these “early” dehydration signals. We used in vivo fiber photometry in the ventral tegmental area and measured phasic dopamine responses to a water-predictive cue. Thirst, but not hunger, potentiated the phasic dopamine response to the water cue. In euvolemic rats, the dipsogenic hormone angiotensin II, but not the orexigenic hormone ghrelin, potentiated the dopamine response similarly to that observed in water-deprived rats. Chemogenetic manipulations of SFOCaMKIIarevealed bidirectional control of phasic dopamine signaling during cued water reward. Taking advantage of within-subject designs, we found predictive relationships between changes in cue-evoked dopamine response and changes in behavioral responses—supporting a role for dopamine in motivation induced by homeostatic need. Collectively, we reveal a putative mechanism for the invigoration of goal-directed behavior: internal milieu communicates to first order, need state-selective circuits to potentiate the mesolimbic dopamine system’s response to cues predictive of restorative stimuli.

Rational regulation of water-seeking effort in rodents

“…This raises the question of where in the brain is computed. The recent explosion of progress in unraveling the neurobiology of thirst ( 13 – 29 ) provides an unprecedented opportunity to link behavioral motivation to known neural mechanisms within an economic theory framework.…”

Rattus economicus: A neural model for rational regulation of water-seeking effort in rodents

“…The recent explosion of progress in unravelling the neurobiology of thirst( 14–28 ) provides an unprecedented opportunity to link behavioral motivation to known neural mechanisms within an economic theory framework. We have proposed that marginal utility MU could be re-interpreted dynamically, and showed that this can further explain the timing of behavioral choices (Figure 5).…”

“…Dopamine circuits have long been implicated in response vigor and willingness to work (47)(48)(49), as well as in representation of marginal utility (50). The SFO GLUT neurons modulate phasic responses in dopamine circuits during drinking (28), so dopamine circuits that encode in this task could inherit this information from SFO. Signals in insular and cingulate cortex related to predicted water need or hedonic water value (24)(25)(26)(27) may also be downstream of computation of in SFO.…”

Heat Stress Responses in Birds: A Review of the Neural Components

“…Hormonal control of thirst and drinking behaviors are primarily mediated by circulating angiotensin II [52], which is upregulated during heat stress [53]. Angiotensin II regulates thirst at the subfornical organ (SFO) [54] and it was hypothesized that thirst signaling occurs through SFO dopaminergic efferents, some of which terminate in the POA [55]. Simplified representation of the mammalian thermoregulatory system.…”