Behavioral and molecular characterization of cell-type specific populations governing fear learning and behavior is a promising avenue for the rational identification of potential therapeutics for fear-related disorde...Behavioral and molecular characterization of cell-type specific populations governing fear learning and behavior is a promising avenue for the rational identification of potential therapeutics for fear-related disorders.Identification of cell-type specific changes in neuronal translation following fear learning allows for targeted pharmacological intervention during fear extinction learning,mirroring possible treatment strategies in humans.Here we identify the central amygdala(Ce A)Drd2-expressing population as a fear-supporting population that is molecularly distinct from other,previously identified fear-supporting CeA populations.Sequencing of actively translating transcripts of Drd2 neurons identifies m RNAs that are differentially regulated following fear learning including Npy5r,Rxrg,Sst5r,Fgf3,Erb B4,Fkbp14,Dlk1,Ssh3 and Adora2a.Direct pharmacological manipulation of NPY5R,RXR,and ADORA2A confirms their importance in fear behavior and validates the present approach of identifying pharmacological targets for the modulation of emotional learning.展开更多
The rat posterodorsal medial amygdala (MePD) is responsive to the orexigenic neuropeptide Y (NPY) and is a putative candidate to participate in neural circuits that modulate feeding behavior. Here, we studied the effe...The rat posterodorsal medial amygdala (MePD) is responsive to the orexigenic neuropeptide Y (NPY) and is a putative candidate to participate in neural circuits that modulate feeding behavior. Here, we studied the effects of intracerebroventricular (icv) microinjection of NPY on the appetitive and food intake behaviors of rats under the paradigm of the self-selection macronutrient isolated diets [high-carbohydrate (high-CHO), high-protein and high-lipid food pellets]. At the same time, Fos expression was also evaluated in the MePD as a marker of local cellular activation. Adult male rats received icv microinjections of NPY (1mg and10mg/5mL, n = 10 and 8, respectively) whereas the control groups either received icv microinjection of artificial cerebrospinal fluid (5mL, n = 8) or underwent sham procedure (n = 8). The data were obtained after a fasting protocol. Feeding behavior was evaluated during a 2 h test period of free access to the selective diets. Rats in all groups preferred the high-CHO diet. Compared to controls, both doses of NPY increased the appetitive behaviors (searching for food and the frequency of attempts to eat any diet) and the percentage of animals eating high-CHO diet. However, only NPY at a dose of 1 μg led to a significant increase in food intake and showed a strong positive correlation with Fos expression in the MePD (p 0.05 in all cases). These new data reveal a biphasic effect of NPY on the appetite and food intake behaviors and suggest that the MePD participates in the NPY-induced feeding behavior in rats.展开更多
目的:阐明下丘脑室旁核(the paraventricu lar nucleus of hypothalam us,PVN)兴奋后的心血管反应及杏仁中央核(the central nucleus of am ygdala,CeA)在此心血管反应中的地位。方法:电刺激SD大鼠中枢核团PVN或CeA,或用核团内微量注射0...目的:阐明下丘脑室旁核(the paraventricu lar nucleus of hypothalam us,PVN)兴奋后的心血管反应及杏仁中央核(the central nucleus of am ygdala,CeA)在此心血管反应中的地位。方法:电刺激SD大鼠中枢核团PVN或CeA,或用核团内微量注射0.5 m o l/L L-谷氨酸(L-Sod iumG lutam ate,L-G lu)方法。同时记录大鼠股动脉血压、平均动脉压(m ean arterial pressure,MAP)、心电图及心率(heart rate,HR)。结果:电刺激一侧PVN后,MAP升高,HR变化不一,以下降为主。大鼠PVN电刺激或微量注射L-G lu均诱发升压反应,心率变化不一。待作用消失后,同侧CeA微量注射L-G lu100n l,注射后平均动脉压上升(10.27±1.80)mmHg,心率变化为(-10.66±8.11)次/m in。待作用消失后,在CeA微量注射0.02 m o l/L的红藻氨酸(KA)100 n l,10 m in后刺激PVN,血压升高(13.78±3.18)mmHg,较注射KA前削弱了(6.57±1.56)mmHg(P<0.05)。结论:PVN兴奋后引起以升压效应为主的心血管反应。杏仁中央核部分介导了其升压反应。展开更多
目的观察完全弗氏佐剂(complete Freund′s adjuvant,CFA)诱导的小鼠慢性炎症性疼痛模型中,单核细胞趋化因子(monocyte chemoattractant protein-1,MCP-1)及其受体CCR2在杏仁核脑区(the central nucleus of the amygdala,CeA)中的表达...目的观察完全弗氏佐剂(complete Freund′s adjuvant,CFA)诱导的小鼠慢性炎症性疼痛模型中,单核细胞趋化因子(monocyte chemoattractant protein-1,MCP-1)及其受体CCR2在杏仁核脑区(the central nucleus of the amygdala,CeA)中的表达变化以及细胞定位情况。方法足底皮下注射CFA 20μL,制作慢性炎症性疼痛模型,用行为学方法检测小鼠的机械性刺激缩爪阈值和热刺激缩爪潜伏期的变化;用real-time PCR法检测造模后不同时间点CeA中MCP-1/CCR2mRNA的表达变化;用Western blot法检测造模后不同时间点CeA中CCR2蛋白的表达变化;选择CFA 7天组,用免疫荧光染色来观察CeA中MCP-1/CCR2蛋白的表达情况,并用双标染色来定位表达MCP-1/CCR2的细胞类型。结果造模1h后小鼠同侧后爪机械性缩爪阈值和热缩爪潜伏期显著降低(P<0.001),并能维持7天以上;造模1天后,CeA中MCP-1mRNA表达量增加(P<0.05),7天达高峰(P<0.01),一直持续到14天(P<0.05);CCR2mRNA从造模6h起表达增加(P<0.05);Western blot结果显示CeA中CCR2蛋白在造模后各个时间点均有表达上调,7天达高峰(P<0.01),一直持续到14天(P<0.01);免疫荧光染色显示,CFA 7天组CeA中MCP-1/CCR2蛋白的表达与生理盐水对照组相比均有增加,而且荧光双标染色显示MCP-1/CCR2蛋白主要与神经元核标记物(NeuN)共标。结论足底皮下注射CFA能诱导小鼠产生机械性触诱发痛和热痛觉过敏,CeA中MCP-1/CCR2mRNA和蛋白表达均增加,且均在神经元表达,提示该部位表达增加的MCP-1/CCR2可能参与炎症性疼痛的维持过程。展开更多
目的:观察降钙素基因相关肽(calcitonin-gene-related peptide,CGRP)样阳性终末在中央杏仁核(cen-tral nucleus of amygdala,CeA)内形成的突触的超微结构。方法:应用免疫荧光组织化学和包埋前免疫电镜等方法,观察CGRP样阳性终末在CeA内...目的:观察降钙素基因相关肽(calcitonin-gene-related peptide,CGRP)样阳性终末在中央杏仁核(cen-tral nucleus of amygdala,CeA)内形成的突触的超微结构。方法:应用免疫荧光组织化学和包埋前免疫电镜等方法,观察CGRP样阳性终末在CeA内所形成的突触分布形式及结构特点。结果:CGRP样阳性终末在中央杏仁核内可以与细胞体、树突干和树突棘等结构形成突触;轴-体突触几乎全为对称性突触,而轴-树突触和轴-棘突触则多为非对称性突触。在所有的非对称性突触里,轴-树突触占84.9%,而轴-棘突触占15.1%。CGRP样阳性轴-树的突触后致密带的平均长度为(790.77±313.55)nm,而轴-棘突触的突触后致密带的平均长度为(723.34±357.20)nm,两者之间没有显著性差异。结论:CGPR样阳性的兴奋性突触尤其是轴-树突触在伤害性信息传递以及痛相关情绪的产生中发挥了重要作用。展开更多
文摘Behavioral and molecular characterization of cell-type specific populations governing fear learning and behavior is a promising avenue for the rational identification of potential therapeutics for fear-related disorders.Identification of cell-type specific changes in neuronal translation following fear learning allows for targeted pharmacological intervention during fear extinction learning,mirroring possible treatment strategies in humans.Here we identify the central amygdala(Ce A)Drd2-expressing population as a fear-supporting population that is molecularly distinct from other,previously identified fear-supporting CeA populations.Sequencing of actively translating transcripts of Drd2 neurons identifies m RNAs that are differentially regulated following fear learning including Npy5r,Rxrg,Sst5r,Fgf3,Erb B4,Fkbp14,Dlk1,Ssh3 and Adora2a.Direct pharmacological manipulation of NPY5R,RXR,and ADORA2A confirms their importance in fear behavior and validates the present approach of identifying pharmacological targets for the modulation of emotional learning.
文摘The rat posterodorsal medial amygdala (MePD) is responsive to the orexigenic neuropeptide Y (NPY) and is a putative candidate to participate in neural circuits that modulate feeding behavior. Here, we studied the effects of intracerebroventricular (icv) microinjection of NPY on the appetitive and food intake behaviors of rats under the paradigm of the self-selection macronutrient isolated diets [high-carbohydrate (high-CHO), high-protein and high-lipid food pellets]. At the same time, Fos expression was also evaluated in the MePD as a marker of local cellular activation. Adult male rats received icv microinjections of NPY (1mg and10mg/5mL, n = 10 and 8, respectively) whereas the control groups either received icv microinjection of artificial cerebrospinal fluid (5mL, n = 8) or underwent sham procedure (n = 8). The data were obtained after a fasting protocol. Feeding behavior was evaluated during a 2 h test period of free access to the selective diets. Rats in all groups preferred the high-CHO diet. Compared to controls, both doses of NPY increased the appetitive behaviors (searching for food and the frequency of attempts to eat any diet) and the percentage of animals eating high-CHO diet. However, only NPY at a dose of 1 μg led to a significant increase in food intake and showed a strong positive correlation with Fos expression in the MePD (p 0.05 in all cases). These new data reveal a biphasic effect of NPY on the appetite and food intake behaviors and suggest that the MePD participates in the NPY-induced feeding behavior in rats.
文摘目的:阐明下丘脑室旁核(the paraventricu lar nucleus of hypothalam us,PVN)兴奋后的心血管反应及杏仁中央核(the central nucleus of am ygdala,CeA)在此心血管反应中的地位。方法:电刺激SD大鼠中枢核团PVN或CeA,或用核团内微量注射0.5 m o l/L L-谷氨酸(L-Sod iumG lutam ate,L-G lu)方法。同时记录大鼠股动脉血压、平均动脉压(m ean arterial pressure,MAP)、心电图及心率(heart rate,HR)。结果:电刺激一侧PVN后,MAP升高,HR变化不一,以下降为主。大鼠PVN电刺激或微量注射L-G lu均诱发升压反应,心率变化不一。待作用消失后,同侧CeA微量注射L-G lu100n l,注射后平均动脉压上升(10.27±1.80)mmHg,心率变化为(-10.66±8.11)次/m in。待作用消失后,在CeA微量注射0.02 m o l/L的红藻氨酸(KA)100 n l,10 m in后刺激PVN,血压升高(13.78±3.18)mmHg,较注射KA前削弱了(6.57±1.56)mmHg(P<0.05)。结论:PVN兴奋后引起以升压效应为主的心血管反应。杏仁中央核部分介导了其升压反应。
文摘目的:观察神经病理性痛条件下细胞外信号调节激酶(extracellular singal-regulated kinase,ERK)对疼痛引起的负性情绪反应的影响。方法:应用Western blot和行为药理学方法,观察腰5脊神经结扎(L5 spinalnerve ligation,SNL)大鼠中央杏仁核外侧囊状部(latero-capsular division of central nucleus of amygdala,CeC)内ERK及磷酸化-ERK(phosphorylated-ERK,p-ERK)的表达情况及ERK磷酸化抑制剂对疼痛引起的负性情绪反应的影响。结果:SNL模型大鼠CeC内p-ERK的表达水平明显升高,与对照组相比,有统计学差异(P<0.05),而总ERK的表达水平则未见组间差异;用超声波检测仪可以检测到SNL大鼠超声发声明显增多,但腹膜腔注射ERK磷酸化的抑制剂U0126后其超声发声被显著抑制。结论:中央杏仁核外侧囊状部内ERK的激活参与了神经病理性痛引起的突触可塑性,在痛相关情绪的产生中发挥了重要作用。
文摘目的:观察降钙素基因相关肽(calcitonin-gene-related peptide,CGRP)样阳性终末在中央杏仁核(cen-tral nucleus of amygdala,CeA)内形成的突触的超微结构。方法:应用免疫荧光组织化学和包埋前免疫电镜等方法,观察CGRP样阳性终末在CeA内所形成的突触分布形式及结构特点。结果:CGRP样阳性终末在中央杏仁核内可以与细胞体、树突干和树突棘等结构形成突触;轴-体突触几乎全为对称性突触,而轴-树突触和轴-棘突触则多为非对称性突触。在所有的非对称性突触里,轴-树突触占84.9%,而轴-棘突触占15.1%。CGRP样阳性轴-树的突触后致密带的平均长度为(790.77±313.55)nm,而轴-棘突触的突触后致密带的平均长度为(723.34±357.20)nm,两者之间没有显著性差异。结论:CGPR样阳性的兴奋性突触尤其是轴-树突触在伤害性信息传递以及痛相关情绪的产生中发挥了重要作用。
