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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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ChR2-dependent drinking requires activation of SFO CamKII positive neurons concurrently with water presentation(a) Representative raster plots illustrating drinking behavior in a wild type animal expressing ChR2-EYFP under the control of CamKII promoter. Trials were performed with photostimulation (blue shadings) delivered before (trials 1–5) or during (trials 6–10) water presentation. The solid arrowhead indicates the first lick in each trial. Each black bar denotes an individual licking event. Note that photostimulation in the absence of water does not lead to drinking after stimulation, even if water is presented a few seconds after the termination of the light stimulation. (b) Quantification of drinking responses in 6 animals expressing AAV-flex-ChR2-EYFP in CamKII-positive neurons before (red bar) and during (black bar) water presentation (Mann-Whitney test, P< 0.003). Animals were tested for 5 trials each, and the total number of licks was averaged across trials. Values are means ± s.e.m.
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Figure 9: ChR2-dependent drinking requires activation of SFO CamKII positive neurons concurrently with water presentation(a) Representative raster plots illustrating drinking behavior in a wild type animal expressing ChR2-EYFP under the control of CamKII promoter. Trials were performed with photostimulation (blue shadings) delivered before (trials 1–5) or during (trials 6–10) water presentation. The solid arrowhead indicates the first lick in each trial. Each black bar denotes an individual licking event. Note that photostimulation in the absence of water does not lead to drinking after stimulation, even if water is presented a few seconds after the termination of the light stimulation. (b) Quantification of drinking responses in 6 animals expressing AAV-flex-ChR2-EYFP in CamKII-positive neurons before (red bar) and during (black bar) water presentation (Mann-Whitney test, P< 0.003). Animals were tested for 5 trials each, and the total number of licks was averaged across trials. Values are means ± s.e.m.

Mentions: To directly test this hypothesis, we utilized an optogenetic approach 16,17. We introduced ChR2 into the SFO by stereotaxic injection of an AAV-ChR2-EYFP construct under the control of the CamkIIa-promoter (Extended Data Figure 4), and examined the effect of photostimulation in awake behaving animals (Figures 1b–e). Remarkably, photoactivation of the SFO CamKII-positive neurons in vivo triggered immediate water seeking behavior followed by intensive drinking (Supplementary Video 1 and Figure 1c). This response was tightly time-locked to the onset of laser stimulation, seen as long as the light stimulus was present, and could be reliably induced in over 90% of the trials (Figure 1d). Upon termination of photostimulation the behavior quickly ceased within a few seconds; light activation of the SFO in the absence of water had no effect on future drinking responses, even if the water was delivered just seconds after the light was switched off (Extended Data Figure 5). Importantly, the light-induced drive to consume water was independent of the internal state of the animal as it was reliably evoked in fully water-satiated mice (Supplementary Video 2). Indeed, during a prolonged regime of laser stimulation water-satiated mice continue to avidly consume water, and may drink nearly 8% of their body weight within 15 min; this is similar to the water consumption seen in the unstimulated animals after 48-hr water restriction (Figure 1e). We note that light stimulation of the SFO did not induce feeding (Supplementary Video 3)


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

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

ChR2-dependent drinking requires activation of SFO CamKII positive neurons concurrently with water presentation(a) Representative raster plots illustrating drinking behavior in a wild type animal expressing ChR2-EYFP under the control of CamKII promoter. Trials were performed with photostimulation (blue shadings) delivered before (trials 1–5) or during (trials 6–10) water presentation. The solid arrowhead indicates the first lick in each trial. Each black bar denotes an individual licking event. Note that photostimulation in the absence of water does not lead to drinking after stimulation, even if water is presented a few seconds after the termination of the light stimulation. (b) Quantification of drinking responses in 6 animals expressing AAV-flex-ChR2-EYFP in CamKII-positive neurons before (red bar) and during (black bar) water presentation (Mann-Whitney test, P< 0.003). Animals were tested for 5 trials each, and the total number of licks was averaged across trials. Values are means ± s.e.m.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 9: ChR2-dependent drinking requires activation of SFO CamKII positive neurons concurrently with water presentation(a) Representative raster plots illustrating drinking behavior in a wild type animal expressing ChR2-EYFP under the control of CamKII promoter. Trials were performed with photostimulation (blue shadings) delivered before (trials 1–5) or during (trials 6–10) water presentation. The solid arrowhead indicates the first lick in each trial. Each black bar denotes an individual licking event. Note that photostimulation in the absence of water does not lead to drinking after stimulation, even if water is presented a few seconds after the termination of the light stimulation. (b) Quantification of drinking responses in 6 animals expressing AAV-flex-ChR2-EYFP in CamKII-positive neurons before (red bar) and during (black bar) water presentation (Mann-Whitney test, P< 0.003). Animals were tested for 5 trials each, and the total number of licks was averaged across trials. Values are means ± s.e.m.
Mentions: To directly test this hypothesis, we utilized an optogenetic approach 16,17. We introduced ChR2 into the SFO by stereotaxic injection of an AAV-ChR2-EYFP construct under the control of the CamkIIa-promoter (Extended Data Figure 4), and examined the effect of photostimulation in awake behaving animals (Figures 1b–e). Remarkably, photoactivation of the SFO CamKII-positive neurons in vivo triggered immediate water seeking behavior followed by intensive drinking (Supplementary Video 1 and Figure 1c). This response was tightly time-locked to the onset of laser stimulation, seen as long as the light stimulus was present, and could be reliably induced in over 90% of the trials (Figure 1d). Upon termination of photostimulation the behavior quickly ceased within a few seconds; light activation of the SFO in the absence of water had no effect on future drinking responses, even if the water was delivered just seconds after the light was switched off (Extended Data Figure 5). Importantly, the light-induced drive to consume water was independent of the internal state of the animal as it was reliably evoked in fully water-satiated mice (Supplementary Video 2). Indeed, during a prolonged regime of laser stimulation water-satiated mice continue to avidly consume water, and may drink nearly 8% of their body weight within 15 min; this is similar to the water consumption seen in the unstimulated animals after 48-hr water restriction (Figure 1e). We note that light stimulation of the SFO did not induce feeding (Supplementary Video 3)

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