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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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Related in: MedlinePlus

Increased impulsiveness and contact time with associated increased autonomic responses in Npbwr1−/− mice during resident-intruder test.(A) Male naive 8-week-old mice were housed individually for 4 weeks before the procedure. The behavior of mice was recorded with a CCD video camera. A randomly chosen male intruder (C57BL/6J) was used only once in each session. The intruder was introduced into the resident cage, and behavior was recorded for 10 min. A variety of social behaviors were scored including the latency to the first aggressive contact (left panel) and time spent in aggressive contact (sniffing, rattling, chasing, mounting, wrestling and fighting) (right panel). Npbwr1−/− mice showed a shorter latency time to contact with the intruder (F1,12 = 5.304, p = 0.040), and longer physical contact with the intruder compared with wild type mice (F1,12 = 6.068, p = 0.030). Data are presented as mean ± SEM (WT n = 6, KO n = 8). Also see movies S1 and S2, which show typical examples of behavior observed during this test. (B) Video tracking system shows traces of intruder (white) and resident (green) during 10 min session of resident-intruder test, showing that Npbwr1−/− mice exhibited more sustained and insistent contact and chasing behavior. Note that the trace of Npbwr1−/− mice is very similar to that of the intruder, reflecting the insistent chasing. (C) Locomotor and cardiovascular responses during resident-intruder test in radiotelemetry-implanted freely moving mice. Activity (upper panels), heart rate (HR; middle panels) and mean arterial pressure (MAP; lower panels) of resident mice (Npbwr1−/− or wild type littermates) during the time course of the resident-intruder test are shown. Intruders (male C57BL/6J mice) were put in the cages at 0 min. Horizontal solid bar indicates the presence of an intruder. Baseline values were defined as the average values of parameters obtained during 10 min immediately prior to the resident-intruder test. Data are presented as mean ± SEM (wild type; n = 4, Npbwr1−/−; n = 5) (*p<0.05, **p<0.01, compared to wild-type). (D) Real time PCR analysis showed that Neuropeptide B (NPB) and Neuropeptide W (NPW) mRNAs in whole brain were upregulated after the resident-intruder test for 60 min. Each level of expression was normalized by the level of Gapdh mRNA (wild type; n = 45, Npbwr1−/−; n = 5).
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pone-0016972-g001: Increased impulsiveness and contact time with associated increased autonomic responses in Npbwr1−/− mice during resident-intruder test.(A) Male naive 8-week-old mice were housed individually for 4 weeks before the procedure. The behavior of mice was recorded with a CCD video camera. A randomly chosen male intruder (C57BL/6J) was used only once in each session. The intruder was introduced into the resident cage, and behavior was recorded for 10 min. A variety of social behaviors were scored including the latency to the first aggressive contact (left panel) and time spent in aggressive contact (sniffing, rattling, chasing, mounting, wrestling and fighting) (right panel). Npbwr1−/− mice showed a shorter latency time to contact with the intruder (F1,12 = 5.304, p = 0.040), and longer physical contact with the intruder compared with wild type mice (F1,12 = 6.068, p = 0.030). Data are presented as mean ± SEM (WT n = 6, KO n = 8). Also see movies S1 and S2, which show typical examples of behavior observed during this test. (B) Video tracking system shows traces of intruder (white) and resident (green) during 10 min session of resident-intruder test, showing that Npbwr1−/− mice exhibited more sustained and insistent contact and chasing behavior. Note that the trace of Npbwr1−/− mice is very similar to that of the intruder, reflecting the insistent chasing. (C) Locomotor and cardiovascular responses during resident-intruder test in radiotelemetry-implanted freely moving mice. Activity (upper panels), heart rate (HR; middle panels) and mean arterial pressure (MAP; lower panels) of resident mice (Npbwr1−/− or wild type littermates) during the time course of the resident-intruder test are shown. Intruders (male C57BL/6J mice) were put in the cages at 0 min. Horizontal solid bar indicates the presence of an intruder. Baseline values were defined as the average values of parameters obtained during 10 min immediately prior to the resident-intruder test. Data are presented as mean ± SEM (wild type; n = 4, Npbwr1−/−; n = 5) (*p<0.05, **p<0.01, compared to wild-type). (D) Real time PCR analysis showed that Neuropeptide B (NPB) and Neuropeptide W (NPW) mRNAs in whole brain were upregulated after the resident-intruder test for 60 min. Each level of expression was normalized by the level of Gapdh mRNA (wild type; n = 45, Npbwr1−/−; n = 5).

Mentions: In the resident-intruder test, male Npbwr1−/− mice showed significantly shorter latency to initial physical contact with the intruder and a significantly longer time in contact with the intruder compared with wild type male mice (C57BL/6J) (Fig. 1A,B). The resident-intruder test also revealed that Npbwr1−/− mice showed characteristic behavior such as persistent chasing during the session (movies S1 and S2). They abandoned their normal caution and tendency to withdraw when confronted with a strange mouse. Instead, they impulsively approached the intruder and showed a greater frequency and duration of contact. When Npbwr1−/− mice were used as intruders, they again showed very fast contact with wild type resident mice and persistent chasing behavior (Fig. S1A).


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)

Increased impulsiveness and contact time with associated increased autonomic responses in Npbwr1−/− mice during resident-intruder test.(A) Male naive 8-week-old mice were housed individually for 4 weeks before the procedure. The behavior of mice was recorded with a CCD video camera. A randomly chosen male intruder (C57BL/6J) was used only once in each session. The intruder was introduced into the resident cage, and behavior was recorded for 10 min. A variety of social behaviors were scored including the latency to the first aggressive contact (left panel) and time spent in aggressive contact (sniffing, rattling, chasing, mounting, wrestling and fighting) (right panel). Npbwr1−/− mice showed a shorter latency time to contact with the intruder (F1,12 = 5.304, p = 0.040), and longer physical contact with the intruder compared with wild type mice (F1,12 = 6.068, p = 0.030). Data are presented as mean ± SEM (WT n = 6, KO n = 8). Also see movies S1 and S2, which show typical examples of behavior observed during this test. (B) Video tracking system shows traces of intruder (white) and resident (green) during 10 min session of resident-intruder test, showing that Npbwr1−/− mice exhibited more sustained and insistent contact and chasing behavior. Note that the trace of Npbwr1−/− mice is very similar to that of the intruder, reflecting the insistent chasing. (C) Locomotor and cardiovascular responses during resident-intruder test in radiotelemetry-implanted freely moving mice. Activity (upper panels), heart rate (HR; middle panels) and mean arterial pressure (MAP; lower panels) of resident mice (Npbwr1−/− or wild type littermates) during the time course of the resident-intruder test are shown. Intruders (male C57BL/6J mice) were put in the cages at 0 min. Horizontal solid bar indicates the presence of an intruder. Baseline values were defined as the average values of parameters obtained during 10 min immediately prior to the resident-intruder test. Data are presented as mean ± SEM (wild type; n = 4, Npbwr1−/−; n = 5) (*p<0.05, **p<0.01, compared to wild-type). (D) Real time PCR analysis showed that Neuropeptide B (NPB) and Neuropeptide W (NPW) mRNAs in whole brain were upregulated after the resident-intruder test for 60 min. Each level of expression was normalized by the level of Gapdh mRNA (wild type; n = 45, Npbwr1−/−; n = 5).
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Related In: Results  -  Collection

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

pone-0016972-g001: Increased impulsiveness and contact time with associated increased autonomic responses in Npbwr1−/− mice during resident-intruder test.(A) Male naive 8-week-old mice were housed individually for 4 weeks before the procedure. The behavior of mice was recorded with a CCD video camera. A randomly chosen male intruder (C57BL/6J) was used only once in each session. The intruder was introduced into the resident cage, and behavior was recorded for 10 min. A variety of social behaviors were scored including the latency to the first aggressive contact (left panel) and time spent in aggressive contact (sniffing, rattling, chasing, mounting, wrestling and fighting) (right panel). Npbwr1−/− mice showed a shorter latency time to contact with the intruder (F1,12 = 5.304, p = 0.040), and longer physical contact with the intruder compared with wild type mice (F1,12 = 6.068, p = 0.030). Data are presented as mean ± SEM (WT n = 6, KO n = 8). Also see movies S1 and S2, which show typical examples of behavior observed during this test. (B) Video tracking system shows traces of intruder (white) and resident (green) during 10 min session of resident-intruder test, showing that Npbwr1−/− mice exhibited more sustained and insistent contact and chasing behavior. Note that the trace of Npbwr1−/− mice is very similar to that of the intruder, reflecting the insistent chasing. (C) Locomotor and cardiovascular responses during resident-intruder test in radiotelemetry-implanted freely moving mice. Activity (upper panels), heart rate (HR; middle panels) and mean arterial pressure (MAP; lower panels) of resident mice (Npbwr1−/− or wild type littermates) during the time course of the resident-intruder test are shown. Intruders (male C57BL/6J mice) were put in the cages at 0 min. Horizontal solid bar indicates the presence of an intruder. Baseline values were defined as the average values of parameters obtained during 10 min immediately prior to the resident-intruder test. Data are presented as mean ± SEM (wild type; n = 4, Npbwr1−/−; n = 5) (*p<0.05, **p<0.01, compared to wild-type). (D) Real time PCR analysis showed that Neuropeptide B (NPB) and Neuropeptide W (NPW) mRNAs in whole brain were upregulated after the resident-intruder test for 60 min. Each level of expression was normalized by the level of Gapdh mRNA (wild type; n = 45, Npbwr1−/−; n = 5).
Mentions: In the resident-intruder test, male Npbwr1−/− mice showed significantly shorter latency to initial physical contact with the intruder and a significantly longer time in contact with the intruder compared with wild type male mice (C57BL/6J) (Fig. 1A,B). The resident-intruder test also revealed that Npbwr1−/− mice showed characteristic behavior such as persistent chasing during the session (movies S1 and S2). They abandoned their normal caution and tendency to withdraw when confronted with a strange mouse. Instead, they impulsively approached the intruder and showed a greater frequency and duration of contact. When Npbwr1−/− mice were used as intruders, they again showed very fast contact with wild type resident mice and persistent chasing behavior (Fig. S1A).

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