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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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Three distinct cell populations in the SFOUsing a combination of data from the Allen Brain Atlas (http://mouse.brain-map.org)32 and a candidate gene approach we identified three genetically separable, non-overlapping populations in the SFO. One population is defined by the expression of nNOS (red); also overlapping with CamKII- and ETV-1-positive cells (see Figures 3a and b). A second one is Vgat-expressing population visualized in a transgenic animal expressing ChR2-EYFP in Vgat-positive neurons (labeled with anti-GFP antibody, green). A third one is characterized by the expression of GFAP (white). Shown are double immunohistochemical staining of nNOS and Vgat-positive neurons (top panel), nNOS and GFAP (middle panel), and GFAP and Vgat-positive neurons (bottom panel). Scale bar, 50 μm.
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Figure 10: Three distinct cell populations in the SFOUsing a combination of data from the Allen Brain Atlas (http://mouse.brain-map.org)32 and a candidate gene approach we identified three genetically separable, non-overlapping populations in the SFO. One population is defined by the expression of nNOS (red); also overlapping with CamKII- and ETV-1-positive cells (see Figures 3a and b). A second one is Vgat-expressing population visualized in a transgenic animal expressing ChR2-EYFP in Vgat-positive neurons (labeled with anti-GFP antibody, green). A third one is characterized by the expression of GFAP (white). Shown are double immunohistochemical staining of nNOS and Vgat-positive neurons (top panel), nNOS and GFAP (middle panel), and GFAP and Vgat-positive neurons (bottom panel). Scale bar, 50 μm.

Mentions: We identified three genetically separable, non-overlapping populations in the SFO (Figures 3a-b and Extended Data Figure 6): an excitatory one defined by expression of CamKII/nNOS (see Extended Data Figure 2), and overlapping with expression of the transcription factor ETV-1, a second one defined by the expression of the vesicular GABA transporter (Vgat), and a third expressing the glial fibrillary acidic protein (GFAP, Figure 3a). As expected, optogenetic stimulation of the ETV-1-positive neurons mimics the effect of activating the CamKII-positive neurons and robustly triggered drinking behavior in water-satiated animals (Figure 3c). The Etv1-Cre mouse line18 used in these experiments is tamoxifen inducible19 (Cre-ER), and correspondingly, the behavior is fully dependent on tamoxifen induction. Photostimulation of the other two populations, did not stimulate drinking (Figure 3c and data not shown).


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

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

Three distinct cell populations in the SFOUsing a combination of data from the Allen Brain Atlas (http://mouse.brain-map.org)32 and a candidate gene approach we identified three genetically separable, non-overlapping populations in the SFO. One population is defined by the expression of nNOS (red); also overlapping with CamKII- and ETV-1-positive cells (see Figures 3a and b). A second one is Vgat-expressing population visualized in a transgenic animal expressing ChR2-EYFP in Vgat-positive neurons (labeled with anti-GFP antibody, green). A third one is characterized by the expression of GFAP (white). Shown are double immunohistochemical staining of nNOS and Vgat-positive neurons (top panel), nNOS and GFAP (middle panel), and GFAP and Vgat-positive neurons (bottom panel). Scale bar, 50 μm.
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Figure 10: Three distinct cell populations in the SFOUsing a combination of data from the Allen Brain Atlas (http://mouse.brain-map.org)32 and a candidate gene approach we identified three genetically separable, non-overlapping populations in the SFO. One population is defined by the expression of nNOS (red); also overlapping with CamKII- and ETV-1-positive cells (see Figures 3a and b). A second one is Vgat-expressing population visualized in a transgenic animal expressing ChR2-EYFP in Vgat-positive neurons (labeled with anti-GFP antibody, green). A third one is characterized by the expression of GFAP (white). Shown are double immunohistochemical staining of nNOS and Vgat-positive neurons (top panel), nNOS and GFAP (middle panel), and GFAP and Vgat-positive neurons (bottom panel). Scale bar, 50 μm.
Mentions: We identified three genetically separable, non-overlapping populations in the SFO (Figures 3a-b and Extended Data Figure 6): an excitatory one defined by expression of CamKII/nNOS (see Extended Data Figure 2), and overlapping with expression of the transcription factor ETV-1, a second one defined by the expression of the vesicular GABA transporter (Vgat), and a third expressing the glial fibrillary acidic protein (GFAP, Figure 3a). As expected, optogenetic stimulation of the ETV-1-positive neurons mimics the effect of activating the CamKII-positive neurons and robustly triggered drinking behavior in water-satiated animals (Figure 3c). The Etv1-Cre mouse line18 used in these experiments is tamoxifen inducible19 (Cre-ER), and correspondingly, the behavior is fully dependent on tamoxifen induction. Photostimulation of the other two populations, did not stimulate drinking (Figure 3c and data not shown).

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