Limits...
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.

Show MeSH

Related in: MedlinePlus

nNOS-positive neurons in the SFO co-express Vglut2, an excitatory neuronal markernNOS antibody staining (green) of the SFO from a Slc17a6-Cre/Ai9 transgenic animal expressing tdTomato in Vglut2-positive neurons (red); the right panel shows a magnified view illustrating the overlap between tdTomato- and nNOS-positive signals. Scale bar, 50 μm.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4401619&req=5

Figure 6: nNOS-positive neurons in the SFO co-express Vglut2, an excitatory neuronal markernNOS antibody staining (green) of the SFO from a Slc17a6-Cre/Ai9 transgenic animal expressing tdTomato in Vglut2-positive neurons (red); the right panel shows a magnified view illustrating the overlap between tdTomato- and nNOS-positive signals. Scale bar, 50 μm.

Mentions: The subfornical organ (SFO) is one of several CVO nuclei activated by thirst-inducing stimuli (e.g. water-deprivation) 1,9. This nucleus lacks the normal blood brain barrier, and has been proposed to function as an osmolality sensor in the brain 1,14,15. We reasoned that if we could identify a selective population of neurons in the SFO that respond to dehydration, they might provide a genetic handle to explore the neural control of thirst and water-drinking behavior. Using Fos as a marker for neuronal activation, we found that approximately 30% of the SFO neurons are strongly labeled with Fos after a 48-hr water restriction regime (no Fos expression was observed under water-satiated conditions, Extended Data Figure 1b). Notably, essentially all of the Fos-labeled cells co-expressed Ca2+/calmodulin-dependent kinase II (CamKII; Figure 1a upper panel), a known marker of excitatory neurons (see Extended Data Figure 2), as well as neuronal nitric oxide synthase (nNOS; Figure 1a lower panel). If these SFO neurons function as key cellular switches in the circuit that drives water consumption, then their activation should trigger water-drinking responses.


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

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

nNOS-positive neurons in the SFO co-express Vglut2, an excitatory neuronal markernNOS antibody staining (green) of the SFO from a Slc17a6-Cre/Ai9 transgenic animal expressing tdTomato in Vglut2-positive neurons (red); the right panel shows a magnified view illustrating the overlap between tdTomato- and nNOS-positive signals. Scale bar, 50 μm.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: nNOS-positive neurons in the SFO co-express Vglut2, an excitatory neuronal markernNOS antibody staining (green) of the SFO from a Slc17a6-Cre/Ai9 transgenic animal expressing tdTomato in Vglut2-positive neurons (red); the right panel shows a magnified view illustrating the overlap between tdTomato- and nNOS-positive signals. Scale bar, 50 μm.
Mentions: The subfornical organ (SFO) is one of several CVO nuclei activated by thirst-inducing stimuli (e.g. water-deprivation) 1,9. This nucleus lacks the normal blood brain barrier, and has been proposed to function as an osmolality sensor in the brain 1,14,15. We reasoned that if we could identify a selective population of neurons in the SFO that respond to dehydration, they might provide a genetic handle to explore the neural control of thirst and water-drinking behavior. Using Fos as a marker for neuronal activation, we found that approximately 30% of the SFO neurons are strongly labeled with Fos after a 48-hr water restriction regime (no Fos expression was observed under water-satiated conditions, Extended Data Figure 1b). Notably, essentially all of the Fos-labeled cells co-expressed Ca2+/calmodulin-dependent kinase II (CamKII; Figure 1a upper panel), a known marker of excitatory neurons (see Extended Data Figure 2), as well as neuronal nitric oxide synthase (nNOS; Figure 1a lower panel). If these SFO neurons function as key cellular switches in the circuit that drives water consumption, then their activation should trigger water-drinking responses.

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