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Thirst driving and suppressing signals encoded by distinct neural populations in the brain.

Oka Y, Ye M, Zuker CS - Nature (2015)

Bottom Line: The light-induced response is highly specific for water, immediate and strictly locked to the laser stimulus.In contrast, activation of a second population of subfornical organ neurons, marked by expression of the vesicular GABA transporter VGAT, drastically suppresses drinking, even in water-craving thirsty animals.These results reveal an innate brain circuit that can turn an animal's water-drinking behaviour on and off, and probably functions as a centre for thirst control in the mammalian brain.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Biochemistry and Molecular Biophysics, Columbia College of Physicians and Surgeons, Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA [2] Department of Neuroscience, Columbia College of Physicians and Surgeons, Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA.

ABSTRACT
Thirst is the basic instinct to drink water. Previously, it was shown that neurons in several circumventricular organs of the hypothalamus are activated by thirst-inducing conditions. Here we identify two distinct, genetically separable neural populations in the subfornical organ that trigger or suppress thirst. We show that optogenetic activation of subfornical organ excitatory neurons, marked by the expression of the transcription factor ETV-1, evokes intense drinking behaviour, and does so even in fully water-satiated animals. The light-induced response is highly specific for water, immediate and strictly locked to the laser stimulus. In contrast, activation of a second population of subfornical organ neurons, marked by expression of the vesicular GABA transporter VGAT, drastically suppresses drinking, even in water-craving thirsty animals. These results reveal an innate brain circuit that can turn an animal's water-drinking behaviour on and off, and probably functions as a centre for thirst control in the mammalian brain.

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Neural projections from Vgat- and Etv-1-positive SFO neuronsSlc32a1-Cre (Vgat-cre; left panel) and Etv1-CreER (right panel) mice were independently injected with AAV-flex-tdTomato in the SFO, and the axon-projections of Vgat-positive and ETV1-positive neurons examined using tdTomato reporter expression (red). Shown are the injection sites (top panels) and representative images of four brain regions receiving input from the SFO: OVLT, the organum vasculosum of the lamina terminalis; MnPO, the median preoptic nucleus; SO, the supraoptic nucleus; PVN, the paraventricular hypothalamic nucleus. Although we cannot preclude additional sites, these four areas exhibited the most prominently labeled projections from the SFO neurons. Scale bars, 200 μm.
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Figure 11: Neural projections from Vgat- and Etv-1-positive SFO neuronsSlc32a1-Cre (Vgat-cre; left panel) and Etv1-CreER (right panel) mice were independently injected with AAV-flex-tdTomato in the SFO, and the axon-projections of Vgat-positive and ETV1-positive neurons examined using tdTomato reporter expression (red). Shown are the injection sites (top panels) and representative images of four brain regions receiving input from the SFO: OVLT, the organum vasculosum of the lamina terminalis; MnPO, the median preoptic nucleus; SO, the supraoptic nucleus; PVN, the paraventricular hypothalamic nucleus. Although we cannot preclude additional sites, these four areas exhibited the most prominently labeled projections from the SFO neurons. Scale bars, 200 μm.

Mentions: In addition to the SFO, dehydration activates several other brain regions 8,15, including the organum vasculosum of the lamina terminalis1 (OVLT), another hypothalamic nucleus lacking the blood brain barrier. Notably, this nucleus has direct connections to the SFO 22,23. Indeed, as an entry to further dissect the circuit for thirst, we have surveyed the axonal projections from the ETV-1 and Vgat-expressing neurons in the SFO. Our results (Extended Data Figure 7) show that both classes of SFO neurons project to the OVLT and the median preoptic nucleus (MnPO). Interestingly, the glutamatergic neurons (i.e. excitatory), unlike the GABAergic neurons, also project to the supraioptic nucleus (SO) and the paravenrtricular hypothalamic nucleus (PVN). Future physiological and behavioral studies should help reveal the role of these nodes in the neural circuitry mediating thirst, and their association with brain centers involved in other motivational states.


Thirst driving and suppressing signals encoded by distinct neural populations in the brain.

Oka Y, Ye M, Zuker CS - Nature (2015)

Neural projections from Vgat- and Etv-1-positive SFO neuronsSlc32a1-Cre (Vgat-cre; left panel) and Etv1-CreER (right panel) mice were independently injected with AAV-flex-tdTomato in the SFO, and the axon-projections of Vgat-positive and ETV1-positive neurons examined using tdTomato reporter expression (red). Shown are the injection sites (top panels) and representative images of four brain regions receiving input from the SFO: OVLT, the organum vasculosum of the lamina terminalis; MnPO, the median preoptic nucleus; SO, the supraoptic nucleus; PVN, the paraventricular hypothalamic nucleus. Although we cannot preclude additional sites, these four areas exhibited the most prominently labeled projections from the SFO neurons. Scale bars, 200 μm.
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Figure 11: Neural projections from Vgat- and Etv-1-positive SFO neuronsSlc32a1-Cre (Vgat-cre; left panel) and Etv1-CreER (right panel) mice were independently injected with AAV-flex-tdTomato in the SFO, and the axon-projections of Vgat-positive and ETV1-positive neurons examined using tdTomato reporter expression (red). Shown are the injection sites (top panels) and representative images of four brain regions receiving input from the SFO: OVLT, the organum vasculosum of the lamina terminalis; MnPO, the median preoptic nucleus; SO, the supraoptic nucleus; PVN, the paraventricular hypothalamic nucleus. Although we cannot preclude additional sites, these four areas exhibited the most prominently labeled projections from the SFO neurons. Scale bars, 200 μm.
Mentions: In addition to the SFO, dehydration activates several other brain regions 8,15, including the organum vasculosum of the lamina terminalis1 (OVLT), another hypothalamic nucleus lacking the blood brain barrier. Notably, this nucleus has direct connections to the SFO 22,23. Indeed, as an entry to further dissect the circuit for thirst, we have surveyed the axonal projections from the ETV-1 and Vgat-expressing neurons in the SFO. Our results (Extended Data Figure 7) show that both classes of SFO neurons project to the OVLT and the median preoptic nucleus (MnPO). Interestingly, the glutamatergic neurons (i.e. excitatory), unlike the GABAergic neurons, also project to the supraioptic nucleus (SO) and the paravenrtricular hypothalamic nucleus (PVN). Future physiological and behavioral studies should help reveal the role of these nodes in the neural circuitry mediating thirst, and their association with brain centers involved in other motivational states.

Bottom Line: The light-induced response is highly specific for water, immediate and strictly locked to the laser stimulus.In contrast, activation of a second population of subfornical organ neurons, marked by expression of the vesicular GABA transporter VGAT, drastically suppresses drinking, even in water-craving thirsty animals.These results reveal an innate brain circuit that can turn an animal's water-drinking behaviour on and off, and probably functions as a centre for thirst control in the mammalian brain.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Biochemistry and Molecular Biophysics, Columbia College of Physicians and Surgeons, Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA [2] Department of Neuroscience, Columbia College of Physicians and Surgeons, Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA.

ABSTRACT
Thirst is the basic instinct to drink water. Previously, it was shown that neurons in several circumventricular organs of the hypothalamus are activated by thirst-inducing conditions. Here we identify two distinct, genetically separable neural populations in the subfornical organ that trigger or suppress thirst. We show that optogenetic activation of subfornical organ excitatory neurons, marked by the expression of the transcription factor ETV-1, evokes intense drinking behaviour, and does so even in fully water-satiated animals. The light-induced response is highly specific for water, immediate and strictly locked to the laser stimulus. In contrast, activation of a second population of subfornical organ neurons, marked by expression of the vesicular GABA transporter VGAT, drastically suppresses drinking, even in water-craving thirsty animals. These results reveal an innate brain circuit that can turn an animal's water-drinking behaviour on and off, and probably functions as a centre for thirst control in the mammalian brain.

Show MeSH
Related in: MedlinePlus