Limits...
Thirst Is Associated with Suppression of Habenula Output and Active Stress Coping: Is there a Role for a Non-canonical Vasopressin-Glutamate Pathway?

Zhang L, Hernández VS, Vázquez-Juárez E, Chay FK, Barrio RA - Front Neural Circuits (2016)

Bottom Line: We demonstrate a direct pathway from hypothalamic paraventricular VP-expressing, glutamatergic magnocellular neurons to the medial division of lateral habenula (LHbM), a region containing GABAergic neurons.In vivo recording and juxtacellular labeling revealed that GABAergic neurons in the LHbM had locally branching axons, and received VP-positive axon terminal contacts on their dendrites.Our results reveal a novel VP-expressing hypothalamus to the LHbM circuit that is likely to evoke GABA-mediated inhibition in the LHbM, which promotes escape behavior during stress coping.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México Ciudad de México, Mexico.

ABSTRACT
Water-homeostasis is a fundamental physiological process for terrestrial life. In vertebrates, thirst drives water intake, but the neuronal circuits that connect the physiology of water regulation with emotional context are poorly understood. Vasopressin (VP) is a prominent messenger in this circuit, as well as L-glutamate. We have investigated the role of a VP circuit and interaction between thirst and motivational behaviors evoked by life-threatening stimuli in rats. We demonstrate a direct pathway from hypothalamic paraventricular VP-expressing, glutamatergic magnocellular neurons to the medial division of lateral habenula (LHbM), a region containing GABAergic neurons. In vivo recording and juxtacellular labeling revealed that GABAergic neurons in the LHbM had locally branching axons, and received VP-positive axon terminal contacts on their dendrites. Water deprivation significantly reduced freezing and immobility behaviors evoked by innate fear and behavioral despair, respectively, accompanied by decreased Fos expression in the lateral habenula. Our results reveal a novel VP-expressing hypothalamus to the LHbM circuit that is likely to evoke GABA-mediated inhibition in the LHbM, which promotes escape behavior during stress coping.

No MeSH data available.


Related in: MedlinePlus

Differential neuronal activation of lateral habenula by cat exposure or forced swimming test (FST) in rats with or without 24 h of water deprivation (WD24) suggested AVP-glutamate pathway activates habenular internal inhibitory mechanisms. Representative photomicrographs of Fos expression patterns: panels (A) and (B) show the Fos expression patterns in the hypothalamic AVP containing paraventricular (PVN), supraoptic (SON) and suprachiasmatic (SCN) nuclei, as a consequence of either cat exposure alone (Aa,Ab) or cat exposure+WD24 (Ba,Bb). Panel Bc shows the Fos expression in PVN after WD24. PVNlmd: lateral magnocellular division of PVN; PVNmpd: medial parvocellular division of PVN; (Ca-c–Ha-c): representative photomicrographs of Fos expression corresponding to each group at each habenular rostro-caudal levels (lettered and framed with the same color code of the histogram). Color-coded histograms and statistical table show Fos+ nuclear counting in whole habenular sections, sampled at three rostro-caudal levels, namely, the rostral (blue), the middle (mid, red) and the caudal (green) of 6 experimental groups: basal (n = 4), WD24 (n = 4), cat exposure (n = 8), cat exposure+WD24 (n = 8), FST (n = 5), FST + WD24 (n = 7). Quantitative results and significance levels are provided in the adjacent table. Scale bars: 100 μm.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4814529&req=5

Figure 8: Differential neuronal activation of lateral habenula by cat exposure or forced swimming test (FST) in rats with or without 24 h of water deprivation (WD24) suggested AVP-glutamate pathway activates habenular internal inhibitory mechanisms. Representative photomicrographs of Fos expression patterns: panels (A) and (B) show the Fos expression patterns in the hypothalamic AVP containing paraventricular (PVN), supraoptic (SON) and suprachiasmatic (SCN) nuclei, as a consequence of either cat exposure alone (Aa,Ab) or cat exposure+WD24 (Ba,Bb). Panel Bc shows the Fos expression in PVN after WD24. PVNlmd: lateral magnocellular division of PVN; PVNmpd: medial parvocellular division of PVN; (Ca-c–Ha-c): representative photomicrographs of Fos expression corresponding to each group at each habenular rostro-caudal levels (lettered and framed with the same color code of the histogram). Color-coded histograms and statistical table show Fos+ nuclear counting in whole habenular sections, sampled at three rostro-caudal levels, namely, the rostral (blue), the middle (mid, red) and the caudal (green) of 6 experimental groups: basal (n = 4), WD24 (n = 4), cat exposure (n = 8), cat exposure+WD24 (n = 8), FST (n = 5), FST + WD24 (n = 7). Quantitative results and significance levels are provided in the adjacent table. Scale bars: 100 μm.

Mentions: The observation of GABAergic interneurons in the LHbMC and their branching patterns prompted us to study the immediate early gene fos protein product Fos expression at three rostro-caudal levels in 6 different groups: basal, WD24, cat exposure, cat exposure+WD24, FST, FST+WD24 (n ≥ 4). Figure 8A showed the Fos activation patterns, due to cat exposure, in the three main vasopressin containing hypothalamic nuclei: PVN, Aa, with low expression in the PVN lateral magnocellular division (PVNlmd) and high expression in the medial parvocellular division (PVNmpd); there was some Fos expression in the SON and in the ventrolateral part of the SCN there was strong activation (this expression pattern was probably due to the circadian time of the rat); the dorsomedial part was mainly inactive (Figure 8Ab and insets). Cat exposure +WD24 activated both the PVNlmd and the PVNmpd (Figure 8Ba). The SON was highly activated so was the SCN (Figure 8Bb and insets). It is worth mentioning that the WD24 per se strongly upregulates the magnocellular vasopressin containing neuron's metabolic activity with an increase of VP plasma concentration from 3 to 7 fold (Dunn et al., 1973; Zhang et al., 2010). Figure 8Bc showed that WD24 alone induced Fos expression in almost all the magnocellular VP neurons. Habenular patterns of neuronal activation measured by Fos+ nuclear accounts were strikingly different between rats with and without WD24, after exposing to cat or to the FST. Under basal conditions, the habenular complex showed low Fos expression in the three rostro-caudal levels, (Figures 8Ca-c and histogram); WD24 activated mainly a selective neuronal population in the medio-central and medio-ventral parts of the lateral habenula (Figures 8Da-c and histogram); cat exposure (Figures 8Ea-c and histogram) or FST (Figures 8Ga-c and histogram) produced vast and diffuse neuronal activation shown as an increase of global Fos expression, whereas WD24 before the behavioral tests reduced the neuronal activation levels significantly (Figures 8Fa-c, Ha–c and histograms “Cat+WD24” and “FST+WD24”). The quantitative data for each group (media ± SEM) and ANOVA results are presented in the table next to the histograms in Figure 8. These significant reductions of global Fos+ nucleus counts in three rostro-caudal LHb levels (rostral, middle, and caudal) indicated that WD24 exerts potent suppression of the functional output of the lateral habenular complex.


Thirst Is Associated with Suppression of Habenula Output and Active Stress Coping: Is there a Role for a Non-canonical Vasopressin-Glutamate Pathway?

Zhang L, Hernández VS, Vázquez-Juárez E, Chay FK, Barrio RA - Front Neural Circuits (2016)

Differential neuronal activation of lateral habenula by cat exposure or forced swimming test (FST) in rats with or without 24 h of water deprivation (WD24) suggested AVP-glutamate pathway activates habenular internal inhibitory mechanisms. Representative photomicrographs of Fos expression patterns: panels (A) and (B) show the Fos expression patterns in the hypothalamic AVP containing paraventricular (PVN), supraoptic (SON) and suprachiasmatic (SCN) nuclei, as a consequence of either cat exposure alone (Aa,Ab) or cat exposure+WD24 (Ba,Bb). Panel Bc shows the Fos expression in PVN after WD24. PVNlmd: lateral magnocellular division of PVN; PVNmpd: medial parvocellular division of PVN; (Ca-c–Ha-c): representative photomicrographs of Fos expression corresponding to each group at each habenular rostro-caudal levels (lettered and framed with the same color code of the histogram). Color-coded histograms and statistical table show Fos+ nuclear counting in whole habenular sections, sampled at three rostro-caudal levels, namely, the rostral (blue), the middle (mid, red) and the caudal (green) of 6 experimental groups: basal (n = 4), WD24 (n = 4), cat exposure (n = 8), cat exposure+WD24 (n = 8), FST (n = 5), FST + WD24 (n = 7). Quantitative results and significance levels are provided in the adjacent table. Scale bars: 100 μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4814529&req=5

Figure 8: Differential neuronal activation of lateral habenula by cat exposure or forced swimming test (FST) in rats with or without 24 h of water deprivation (WD24) suggested AVP-glutamate pathway activates habenular internal inhibitory mechanisms. Representative photomicrographs of Fos expression patterns: panels (A) and (B) show the Fos expression patterns in the hypothalamic AVP containing paraventricular (PVN), supraoptic (SON) and suprachiasmatic (SCN) nuclei, as a consequence of either cat exposure alone (Aa,Ab) or cat exposure+WD24 (Ba,Bb). Panel Bc shows the Fos expression in PVN after WD24. PVNlmd: lateral magnocellular division of PVN; PVNmpd: medial parvocellular division of PVN; (Ca-c–Ha-c): representative photomicrographs of Fos expression corresponding to each group at each habenular rostro-caudal levels (lettered and framed with the same color code of the histogram). Color-coded histograms and statistical table show Fos+ nuclear counting in whole habenular sections, sampled at three rostro-caudal levels, namely, the rostral (blue), the middle (mid, red) and the caudal (green) of 6 experimental groups: basal (n = 4), WD24 (n = 4), cat exposure (n = 8), cat exposure+WD24 (n = 8), FST (n = 5), FST + WD24 (n = 7). Quantitative results and significance levels are provided in the adjacent table. Scale bars: 100 μm.
Mentions: The observation of GABAergic interneurons in the LHbMC and their branching patterns prompted us to study the immediate early gene fos protein product Fos expression at three rostro-caudal levels in 6 different groups: basal, WD24, cat exposure, cat exposure+WD24, FST, FST+WD24 (n ≥ 4). Figure 8A showed the Fos activation patterns, due to cat exposure, in the three main vasopressin containing hypothalamic nuclei: PVN, Aa, with low expression in the PVN lateral magnocellular division (PVNlmd) and high expression in the medial parvocellular division (PVNmpd); there was some Fos expression in the SON and in the ventrolateral part of the SCN there was strong activation (this expression pattern was probably due to the circadian time of the rat); the dorsomedial part was mainly inactive (Figure 8Ab and insets). Cat exposure +WD24 activated both the PVNlmd and the PVNmpd (Figure 8Ba). The SON was highly activated so was the SCN (Figure 8Bb and insets). It is worth mentioning that the WD24 per se strongly upregulates the magnocellular vasopressin containing neuron's metabolic activity with an increase of VP plasma concentration from 3 to 7 fold (Dunn et al., 1973; Zhang et al., 2010). Figure 8Bc showed that WD24 alone induced Fos expression in almost all the magnocellular VP neurons. Habenular patterns of neuronal activation measured by Fos+ nuclear accounts were strikingly different between rats with and without WD24, after exposing to cat or to the FST. Under basal conditions, the habenular complex showed low Fos expression in the three rostro-caudal levels, (Figures 8Ca-c and histogram); WD24 activated mainly a selective neuronal population in the medio-central and medio-ventral parts of the lateral habenula (Figures 8Da-c and histogram); cat exposure (Figures 8Ea-c and histogram) or FST (Figures 8Ga-c and histogram) produced vast and diffuse neuronal activation shown as an increase of global Fos expression, whereas WD24 before the behavioral tests reduced the neuronal activation levels significantly (Figures 8Fa-c, Ha–c and histograms “Cat+WD24” and “FST+WD24”). The quantitative data for each group (media ± SEM) and ANOVA results are presented in the table next to the histograms in Figure 8. These significant reductions of global Fos+ nucleus counts in three rostro-caudal LHb levels (rostral, middle, and caudal) indicated that WD24 exerts potent suppression of the functional output of the lateral habenular complex.

Bottom Line: We demonstrate a direct pathway from hypothalamic paraventricular VP-expressing, glutamatergic magnocellular neurons to the medial division of lateral habenula (LHbM), a region containing GABAergic neurons.In vivo recording and juxtacellular labeling revealed that GABAergic neurons in the LHbM had locally branching axons, and received VP-positive axon terminal contacts on their dendrites.Our results reveal a novel VP-expressing hypothalamus to the LHbM circuit that is likely to evoke GABA-mediated inhibition in the LHbM, which promotes escape behavior during stress coping.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México Ciudad de México, Mexico.

ABSTRACT
Water-homeostasis is a fundamental physiological process for terrestrial life. In vertebrates, thirst drives water intake, but the neuronal circuits that connect the physiology of water regulation with emotional context are poorly understood. Vasopressin (VP) is a prominent messenger in this circuit, as well as L-glutamate. We have investigated the role of a VP circuit and interaction between thirst and motivational behaviors evoked by life-threatening stimuli in rats. We demonstrate a direct pathway from hypothalamic paraventricular VP-expressing, glutamatergic magnocellular neurons to the medial division of lateral habenula (LHbM), a region containing GABAergic neurons. In vivo recording and juxtacellular labeling revealed that GABAergic neurons in the LHbM had locally branching axons, and received VP-positive axon terminal contacts on their dendrites. Water deprivation significantly reduced freezing and immobility behaviors evoked by innate fear and behavioral despair, respectively, accompanied by decreased Fos expression in the lateral habenula. Our results reveal a novel VP-expressing hypothalamus to the LHbM circuit that is likely to evoke GABA-mediated inhibition in the LHbM, which promotes escape behavior during stress coping.

No MeSH data available.


Related in: MedlinePlus