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Critical role of neuropeptides B/W receptor 1 signaling in social behavior and fear memory.

Nagata-Kuroiwa R, Furutani N, Hara J, Hondo M, Ishii M, Abe T, Mieda M, Tsujino N, Motoike T, Yanagawa Y, Kuwaki T, Yamamoto M, Yanagisawa M, Sakurai T - PLoS ONE (2011)

Bottom Line: These data suggest that NPBWR1 plays a critical role in limbic system function and stress responses.Histological and electrophysiological studies showed that NPBWR1 acts as an inhibitory regulator on a subpopulation of GABAergic neurons in the lateral division of the CeA and terminates stress responses.These findings suggest important roles of NPBWR1 in regulating amygdala function during physical and social stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Neuroscience and Integrative Physiology, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.

ABSTRACT
Neuropeptide B/W receptor 1 (NPBWR1) is a G-protein coupled receptor, which was initially reported as an orphan receptor, and whose ligands were identified by this and other groups in 2002 and 2003. To examine the physiological roles of NPBWR1, we examined phenotype of Npbwr1⁻/⁻ mice. When presented with an intruder mouse, Npbwr1⁻/⁻ mice showed impulsive contact with the strange mice, produced more intense approaches toward them, and had longer contact and chasing time along with greater and sustained elevation of heart rate and blood pressure compared to wild type mice. Npbwr1⁻/⁻ mice also showed increased autonomic and neuroendocrine responses to physical stress, suggesting that impairment of NPBWR1 leads to stress vulnerability. We also observed that these mice show abnormality in the contextual fear conditioning test. These data suggest that NPBWR1 plays a critical role in limbic system function and stress responses. Histological and electrophysiological studies showed that NPBWR1 acts as an inhibitory regulator on a subpopulation of GABAergic neurons in the lateral division of the CeA and terminates stress responses. These findings suggest important roles of NPBWR1 in regulating amygdala function during physical and social stress.

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Schematic model of regulatory mechanism by which neuropeptide B/W regulates activity of amygdala neurons.(A) NPB or NPW acts on NPBWR1 expressed on projection neurons in the CeAl, which could signal to the brain stem and BST to elicit emotion-related autonomic and neuroendocrine responses. Some GABAergic interneurons in the CeAl also express Npbwr1. Therefore, NPB/W signaling could modulate amygdala function in multiple pathways. (B) When the NPB/W system is activated, some of the projection neurons in the CeAl might be inhibited, while other projection neurons might be disinhibited through inhibition of GABAergic interneurons. For example, output to autonomic/neuroendocrine pathways could be inhibited, while behavioral output might be activated. (C) NPB/W system dysfunction may result in exaggerated autonomic/neuroendocrine responses along with impaired behavioral response.
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pone-0016972-g005: Schematic model of regulatory mechanism by which neuropeptide B/W regulates activity of amygdala neurons.(A) NPB or NPW acts on NPBWR1 expressed on projection neurons in the CeAl, which could signal to the brain stem and BST to elicit emotion-related autonomic and neuroendocrine responses. Some GABAergic interneurons in the CeAl also express Npbwr1. Therefore, NPB/W signaling could modulate amygdala function in multiple pathways. (B) When the NPB/W system is activated, some of the projection neurons in the CeAl might be inhibited, while other projection neurons might be disinhibited through inhibition of GABAergic interneurons. For example, output to autonomic/neuroendocrine pathways could be inhibited, while behavioral output might be activated. (C) NPB/W system dysfunction may result in exaggerated autonomic/neuroendocrine responses along with impaired behavioral response.

Mentions: Peptidergic neuromodulation is a relatively slow and sustained process as compared to the glutamatergic and GABAergic systems. We speculate that the NPB/W system might play a role in regulating amygdala function over a relatively longer time scale. Both Npb and Npw mRNAs were increased under stressful conditions induced by the resident-intruder paradigm, suggesting that this system might work as a feedback regulator of the amygdala by inhibiting projection neurons in the CeAl (Fig. 1D). In addition, some of the GABAergic interneurons within the CeAl also expressed Npbwr1 (Fig. 4C, D). This suggests an intriguing possibility that NPB/W regulates amygdala networks by inhibiting some specific outputs while disinhibiting others, thereby helping to select proper behavioral and neuroendocrine responses [14] (Fig. 5). This model may explain why Npbwr1−/− mice showed decreased fear-related behavioral responses to complex contexts such as social interaction and contextual fear, but showed increased sympathetic responses to various stresses. Russel and Mehrabian classified emotions into three dimensions of factors; valence (pleasure-displeasure), arousal (autonomic response), and dominance [21]. The NPB/W system might regulate emotions in the arousal and dominance scales according to the animal's environment which contains a relatively complex context.


Critical role of neuropeptides B/W receptor 1 signaling in social behavior and fear memory.

Nagata-Kuroiwa R, Furutani N, Hara J, Hondo M, Ishii M, Abe T, Mieda M, Tsujino N, Motoike T, Yanagawa Y, Kuwaki T, Yamamoto M, Yanagisawa M, Sakurai T - PLoS ONE (2011)

Schematic model of regulatory mechanism by which neuropeptide B/W regulates activity of amygdala neurons.(A) NPB or NPW acts on NPBWR1 expressed on projection neurons in the CeAl, which could signal to the brain stem and BST to elicit emotion-related autonomic and neuroendocrine responses. Some GABAergic interneurons in the CeAl also express Npbwr1. Therefore, NPB/W signaling could modulate amygdala function in multiple pathways. (B) When the NPB/W system is activated, some of the projection neurons in the CeAl might be inhibited, while other projection neurons might be disinhibited through inhibition of GABAergic interneurons. For example, output to autonomic/neuroendocrine pathways could be inhibited, while behavioral output might be activated. (C) NPB/W system dysfunction may result in exaggerated autonomic/neuroendocrine responses along with impaired behavioral response.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3044739&req=5

pone-0016972-g005: Schematic model of regulatory mechanism by which neuropeptide B/W regulates activity of amygdala neurons.(A) NPB or NPW acts on NPBWR1 expressed on projection neurons in the CeAl, which could signal to the brain stem and BST to elicit emotion-related autonomic and neuroendocrine responses. Some GABAergic interneurons in the CeAl also express Npbwr1. Therefore, NPB/W signaling could modulate amygdala function in multiple pathways. (B) When the NPB/W system is activated, some of the projection neurons in the CeAl might be inhibited, while other projection neurons might be disinhibited through inhibition of GABAergic interneurons. For example, output to autonomic/neuroendocrine pathways could be inhibited, while behavioral output might be activated. (C) NPB/W system dysfunction may result in exaggerated autonomic/neuroendocrine responses along with impaired behavioral response.
Mentions: Peptidergic neuromodulation is a relatively slow and sustained process as compared to the glutamatergic and GABAergic systems. We speculate that the NPB/W system might play a role in regulating amygdala function over a relatively longer time scale. Both Npb and Npw mRNAs were increased under stressful conditions induced by the resident-intruder paradigm, suggesting that this system might work as a feedback regulator of the amygdala by inhibiting projection neurons in the CeAl (Fig. 1D). In addition, some of the GABAergic interneurons within the CeAl also expressed Npbwr1 (Fig. 4C, D). This suggests an intriguing possibility that NPB/W regulates amygdala networks by inhibiting some specific outputs while disinhibiting others, thereby helping to select proper behavioral and neuroendocrine responses [14] (Fig. 5). This model may explain why Npbwr1−/− mice showed decreased fear-related behavioral responses to complex contexts such as social interaction and contextual fear, but showed increased sympathetic responses to various stresses. Russel and Mehrabian classified emotions into three dimensions of factors; valence (pleasure-displeasure), arousal (autonomic response), and dominance [21]. The NPB/W system might regulate emotions in the arousal and dominance scales according to the animal's environment which contains a relatively complex context.

Bottom Line: These data suggest that NPBWR1 plays a critical role in limbic system function and stress responses.Histological and electrophysiological studies showed that NPBWR1 acts as an inhibitory regulator on a subpopulation of GABAergic neurons in the lateral division of the CeA and terminates stress responses.These findings suggest important roles of NPBWR1 in regulating amygdala function during physical and social stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Neuroscience and Integrative Physiology, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.

ABSTRACT
Neuropeptide B/W receptor 1 (NPBWR1) is a G-protein coupled receptor, which was initially reported as an orphan receptor, and whose ligands were identified by this and other groups in 2002 and 2003. To examine the physiological roles of NPBWR1, we examined phenotype of Npbwr1⁻/⁻ mice. When presented with an intruder mouse, Npbwr1⁻/⁻ mice showed impulsive contact with the strange mice, produced more intense approaches toward them, and had longer contact and chasing time along with greater and sustained elevation of heart rate and blood pressure compared to wild type mice. Npbwr1⁻/⁻ mice also showed increased autonomic and neuroendocrine responses to physical stress, suggesting that impairment of NPBWR1 leads to stress vulnerability. We also observed that these mice show abnormality in the contextual fear conditioning test. These data suggest that NPBWR1 plays a critical role in limbic system function and stress responses. Histological and electrophysiological studies showed that NPBWR1 acts as an inhibitory regulator on a subpopulation of GABAergic neurons in the lateral division of the CeA and terminates stress responses. These findings suggest important roles of NPBWR1 in regulating amygdala function during physical and social stress.

Show MeSH
Related in: MedlinePlus