Mandela Prashant, Yan Yan, LaRese Taylor, Eipper Betty A, Mains Richard E
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-3401, United States.
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-3401, United States.
Horm Behav. 2014 Jul;66(2):430-8. doi: 10.1016/j.yhbeh.2014.07.001. Epub 2014 Jul 9.
Kalirin, a Rho GDP/GTP exchange factor for Rac1 and RhoG, is known to play an essential role in the formation and maintenance of excitatory synapses and in the secretion of neuropeptides. Mice unable to express any of the isoforms of Kalrn in cells that produce POMC at any time during development (POMC cells) exhibited reduced anxiety-like behavior and reduced acquisition of passive avoidance behavior, along with sex-specific alteration in the corticosterone response to restraint stress. Strikingly, lack of Kalrn expression in POMC cells closely mimicked the effects of global Kalrn knockout on anxiety-like behavior and passive avoidance conditioning without causing the other deficits noted in Kalrn knockout mice. Our data suggest that deficits in excitatory inputs onto POMC neurons are responsible for the behavioral phenotypes observed.
Kalirin是Rac1和RhoG的一种Rho GDP / GTP交换因子，已知其在兴奋性突触的形成和维持以及神经肽分泌中起关键作用。在发育过程中的任何时候都无法在产生促肾上腺皮质激素原（POMC）的细胞（POMC细胞）中表达任何Kalrn亚型的小鼠，表现出焦虑样行为减少和被动回避行为的习得减少，以及对束缚应激的皮质酮反应的性别特异性改变。引人注目的是，POMC细胞中缺乏Kalrn表达与全局Kalrn基因敲除对焦虑样行为和被动回避条件反射的影响非常相似，而不会导致Kalrn基因敲除小鼠中出现的其他缺陷。我们的数据表明，POMC神经元上兴奋性输入的缺陷是观察到的行为表型的原因。
