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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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Angiotensin receptor AT1 is enriched in ETV-1+ neurons in the SFOQuantitative PCR analysis of gene expression in three groups of neurons: ETV-1+ neurons from the SFO, ETV-1+ from the cerebral cortex31, and Vgat+ neurons from the SFO. Individual data points were normalized to the levels of GAPDH. Shown are the qPCR results for ETV1, nNOS, Vgat and AT1 in the three different samples; data is presented for each gene as its relative abundance compared to the tissue with the lowest level of expression (for example nNOS is expressed 10x more abundantly in ETV1-positive neurons from the cortex than in Vgat neurons from the SFO, and 1000x more abundantly in ETV-1 positive neurons from the SFO than the cortex). Note, that AT1 is highly enriched in ETV-1+ SFO neurons. N.D.: not detected. Values are means ± s.e.m (n=3 technical replicates)
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Figure 7: Angiotensin receptor AT1 is enriched in ETV-1+ neurons in the SFOQuantitative PCR analysis of gene expression in three groups of neurons: ETV-1+ neurons from the SFO, ETV-1+ from the cerebral cortex31, and Vgat+ neurons from the SFO. Individual data points were normalized to the levels of GAPDH. Shown are the qPCR results for ETV1, nNOS, Vgat and AT1 in the three different samples; data is presented for each gene as its relative abundance compared to the tissue with the lowest level of expression (for example nNOS is expressed 10x more abundantly in ETV1-positive neurons from the cortex than in Vgat neurons from the SFO, and 1000x more abundantly in ETV-1 positive neurons from the SFO than the cortex). Note, that AT1 is highly enriched in ETV-1+ SFO neurons. N.D.: not detected. Values are means ± s.e.m (n=3 technical replicates)

Mentions: We used a combination of genetic and optogenetic tools in awake, behaving animals to demonstrate that the ETV-1- and Vgat-positive neurons of the SFO evoke or suppress the motivation to drink, respectively. We showed that activation of either population instantly triggered the behavior, be it water-seeking and drinking in normal or water-satiated animals, or strong suppression of drinking in thirsty animals; these responses are selective to water-drinking, with no effect on feeding or salt appetite. Significantly, most of the neurons in the SFO are either ETV-1 positive or VGAT-positive (Figure 3), strongly arguing that the SFO is a dedicated brain system for thirst, functioning possibly at the interface between the physiological/internal state of the organism and the motivation to drink water. Interestingly, the ETV-1 neuronal population selectively expresses the angiotensin receptor AT1 (Extended Data Figure 3), identifying them as a possible target of angiotensin-mediated drinking responses9–11.


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

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

Angiotensin receptor AT1 is enriched in ETV-1+ neurons in the SFOQuantitative PCR analysis of gene expression in three groups of neurons: ETV-1+ neurons from the SFO, ETV-1+ from the cerebral cortex31, and Vgat+ neurons from the SFO. Individual data points were normalized to the levels of GAPDH. Shown are the qPCR results for ETV1, nNOS, Vgat and AT1 in the three different samples; data is presented for each gene as its relative abundance compared to the tissue with the lowest level of expression (for example nNOS is expressed 10x more abundantly in ETV1-positive neurons from the cortex than in Vgat neurons from the SFO, and 1000x more abundantly in ETV-1 positive neurons from the SFO than the cortex). Note, that AT1 is highly enriched in ETV-1+ SFO neurons. N.D.: not detected. Values are means ± s.e.m (n=3 technical replicates)
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4401619&req=5

Figure 7: Angiotensin receptor AT1 is enriched in ETV-1+ neurons in the SFOQuantitative PCR analysis of gene expression in three groups of neurons: ETV-1+ neurons from the SFO, ETV-1+ from the cerebral cortex31, and Vgat+ neurons from the SFO. Individual data points were normalized to the levels of GAPDH. Shown are the qPCR results for ETV1, nNOS, Vgat and AT1 in the three different samples; data is presented for each gene as its relative abundance compared to the tissue with the lowest level of expression (for example nNOS is expressed 10x more abundantly in ETV1-positive neurons from the cortex than in Vgat neurons from the SFO, and 1000x more abundantly in ETV-1 positive neurons from the SFO than the cortex). Note, that AT1 is highly enriched in ETV-1+ SFO neurons. N.D.: not detected. Values are means ± s.e.m (n=3 technical replicates)
Mentions: We used a combination of genetic and optogenetic tools in awake, behaving animals to demonstrate that the ETV-1- and Vgat-positive neurons of the SFO evoke or suppress the motivation to drink, respectively. We showed that activation of either population instantly triggered the behavior, be it water-seeking and drinking in normal or water-satiated animals, or strong suppression of drinking in thirsty animals; these responses are selective to water-drinking, with no effect on feeding or salt appetite. Significantly, most of the neurons in the SFO are either ETV-1 positive or VGAT-positive (Figure 3), strongly arguing that the SFO is a dedicated brain system for thirst, functioning possibly at the interface between the physiological/internal state of the organism and the motivation to drink water. Interestingly, the ETV-1 neuronal population selectively expresses the angiotensin receptor AT1 (Extended Data Figure 3), identifying them as a possible target of angiotensin-mediated drinking responses9–11.

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