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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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Activation of Vgat-positive neurons in the SFO suppresses thirst(a) Drinking behavior of a 24-hr water-deprived animal expressing ChR2 in Vgat-positive neurons. Trials were performed in the absence (trials1–5) or presence of photostimulation (trial 6–10). The solid arrowhead indicates the time of water presentation, and the open arrowheads mark the first lick; animals were allowed to lick for 5 s following the first lick in each trial. Light stimulation (blue shading) was started 10 s prior to water presentation, and maintained until the end of the 5 s licking window. The boxes on the right show an enlargement of these 10 trials, each aligned to the first lick. Note the strong suppression during photostimulation. (b) Graph quantifying the degree of suppression animals expressing AAV-flex-ChR2-EYFP in Vgat-positive neurons of the SFO (Slc32a1-Cre24) with or without light stimulation (Mann-Whitney test, P< 0.002; n=8). Also shown are wild type control mice infected with the same AAV-flex-ChR2-EYFP construct (n=5). Animals were tested for >5 trials each, and the total number of licks was averaged across trials. Photostimulation of the GFAP-positive population had no effect on drinking (data not shown). (c) Activation of Vgat-positive neurons suppresses drinking behavior even if animals were actively drinking. The plot illustrates the drinking response of a thirsty animal in 5 tests, before and during photostimulation (blue shading); the trials were aligned 3 s before photostimulation. (de) Photostimulation of Vgat-positive neurons did not suppress salt appetite in salt- depleted animals (150 mM NaCl), or sugar intake in hungry animals (300 mM sucrose); values are means ± s.e.m (n=7).
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Figure 4: Activation of Vgat-positive neurons in the SFO suppresses thirst(a) Drinking behavior of a 24-hr water-deprived animal expressing ChR2 in Vgat-positive neurons. Trials were performed in the absence (trials1–5) or presence of photostimulation (trial 6–10). The solid arrowhead indicates the time of water presentation, and the open arrowheads mark the first lick; animals were allowed to lick for 5 s following the first lick in each trial. Light stimulation (blue shading) was started 10 s prior to water presentation, and maintained until the end of the 5 s licking window. The boxes on the right show an enlargement of these 10 trials, each aligned to the first lick. Note the strong suppression during photostimulation. (b) Graph quantifying the degree of suppression animals expressing AAV-flex-ChR2-EYFP in Vgat-positive neurons of the SFO (Slc32a1-Cre24) with or without light stimulation (Mann-Whitney test, P< 0.002; n=8). Also shown are wild type control mice infected with the same AAV-flex-ChR2-EYFP construct (n=5). Animals were tested for >5 trials each, and the total number of licks was averaged across trials. Photostimulation of the GFAP-positive population had no effect on drinking (data not shown). (c) Activation of Vgat-positive neurons suppresses drinking behavior even if animals were actively drinking. The plot illustrates the drinking response of a thirsty animal in 5 tests, before and during photostimulation (blue shading); the trials were aligned 3 s before photostimulation. (de) Photostimulation of Vgat-positive neurons did not suppress salt appetite in salt- depleted animals (150 mM NaCl), or sugar intake in hungry animals (300 mM sucrose); values are means ± s.e.m (n=7).

Mentions: Given that the CamKII/ETV1-positive neurons provide a “thirst-ON” signal, we wondered whether one of the other cell classes might encode a “thirst-OFF” signal. Indeed, activation of the Vgat-positive neurons significantly suppressed water intake in thirsty animals (>80% lick suppression); the effect was time-locked to the laser stimulation, and observed in all Vgat ChR2-expressing animals tested (Figures 4a and b). Significantly, the suppression was as effective in thirsty animals that were actively drinking water, as it was in thirsty animals that have not yet sampled water (compare Figures 4a and 4c)


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

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

Activation of Vgat-positive neurons in the SFO suppresses thirst(a) Drinking behavior of a 24-hr water-deprived animal expressing ChR2 in Vgat-positive neurons. Trials were performed in the absence (trials1–5) or presence of photostimulation (trial 6–10). The solid arrowhead indicates the time of water presentation, and the open arrowheads mark the first lick; animals were allowed to lick for 5 s following the first lick in each trial. Light stimulation (blue shading) was started 10 s prior to water presentation, and maintained until the end of the 5 s licking window. The boxes on the right show an enlargement of these 10 trials, each aligned to the first lick. Note the strong suppression during photostimulation. (b) Graph quantifying the degree of suppression animals expressing AAV-flex-ChR2-EYFP in Vgat-positive neurons of the SFO (Slc32a1-Cre24) with or without light stimulation (Mann-Whitney test, P< 0.002; n=8). Also shown are wild type control mice infected with the same AAV-flex-ChR2-EYFP construct (n=5). Animals were tested for >5 trials each, and the total number of licks was averaged across trials. Photostimulation of the GFAP-positive population had no effect on drinking (data not shown). (c) Activation of Vgat-positive neurons suppresses drinking behavior even if animals were actively drinking. The plot illustrates the drinking response of a thirsty animal in 5 tests, before and during photostimulation (blue shading); the trials were aligned 3 s before photostimulation. (de) Photostimulation of Vgat-positive neurons did not suppress salt appetite in salt- depleted animals (150 mM NaCl), or sugar intake in hungry animals (300 mM sucrose); values are means ± s.e.m (n=7).
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Related In: Results  -  Collection

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

Figure 4: Activation of Vgat-positive neurons in the SFO suppresses thirst(a) Drinking behavior of a 24-hr water-deprived animal expressing ChR2 in Vgat-positive neurons. Trials were performed in the absence (trials1–5) or presence of photostimulation (trial 6–10). The solid arrowhead indicates the time of water presentation, and the open arrowheads mark the first lick; animals were allowed to lick for 5 s following the first lick in each trial. Light stimulation (blue shading) was started 10 s prior to water presentation, and maintained until the end of the 5 s licking window. The boxes on the right show an enlargement of these 10 trials, each aligned to the first lick. Note the strong suppression during photostimulation. (b) Graph quantifying the degree of suppression animals expressing AAV-flex-ChR2-EYFP in Vgat-positive neurons of the SFO (Slc32a1-Cre24) with or without light stimulation (Mann-Whitney test, P< 0.002; n=8). Also shown are wild type control mice infected with the same AAV-flex-ChR2-EYFP construct (n=5). Animals were tested for >5 trials each, and the total number of licks was averaged across trials. Photostimulation of the GFAP-positive population had no effect on drinking (data not shown). (c) Activation of Vgat-positive neurons suppresses drinking behavior even if animals were actively drinking. The plot illustrates the drinking response of a thirsty animal in 5 tests, before and during photostimulation (blue shading); the trials were aligned 3 s before photostimulation. (de) Photostimulation of Vgat-positive neurons did not suppress salt appetite in salt- depleted animals (150 mM NaCl), or sugar intake in hungry animals (300 mM sucrose); values are means ± s.e.m (n=7).
Mentions: Given that the CamKII/ETV1-positive neurons provide a “thirst-ON” signal, we wondered whether one of the other cell classes might encode a “thirst-OFF” signal. Indeed, activation of the Vgat-positive neurons significantly suppressed water intake in thirsty animals (>80% lick suppression); the effect was time-locked to the laser stimulation, and observed in all Vgat ChR2-expressing animals tested (Figures 4a and b). Significantly, the suppression was as effective in thirsty animals that were actively drinking water, as it was in thirsty animals that have not yet sampled water (compare Figures 4a and 4c)

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