Gutiérrez H, Miranda M I, Bermúdez-Rattoni F
Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 Mexico D. F., Mexico.
J Neurosci. 1997 May 15;17(10):3796-803. doi: 10.1523/JNEUROSCI.17-10-03796.1997.
Cholinergic basal forebrain (CBF ) neurons have been shown to respond in vivo to exogenous administration of NGF. Although neurotrophins and their receptors are widely expressed in the CNS, little data exist for the physiological significance of endogenous neurotrophin signaling in CNS neurons. To test directly whether cortically derived NGF is functionally required for the cholinergic functions mediated by the cerebral cortex, repeated injections of anti-NGF mAbs were locally applied into the insular cortex (IC) of rats. The biochemical results, using an in vivo microdialysis technique, showed a dramatic lack of extracellular release of acetylcholine after high potassium stimulation compared with controls. Furthermore, by using small injections of the neurotracer fluorogold, we found a corresponding disruption in the connectivity between the IC and the CBF. Behavioral experiments showed that the NGF antibodies applied into the IC produced a significant disruption on the acquisition of conditioned taste aversion and inhibitory avoidance learning. However, the same animals were able to recall the taste aversion when the conditioning trial was established before injections of NGF antibodies. Given these results, it seems that cortical cholinergic functions are actively dependent on locally derived NGF in the adult normal brain, and that the cholinergic activity from the CBF is not necessary for recalling aversive stimuli, but is necessary for the acquisition of aversively motivated conditionings.
胆碱能基底前脑（CBF）神经元已被证明在体内对外源性给予神经生长因子（NGF）有反应。尽管神经营养因子及其受体在中枢神经系统中广泛表达，但关于中枢神经系统神经元内源性神经营养因子信号传导的生理意义的数据却很少。为了直接测试皮质来源的NGF对于大脑皮质介导的胆碱能功能是否在功能上是必需的，将抗NGF单克隆抗体重复注射到大鼠的岛叶皮质（IC）中。使用体内微透析技术的生化结果显示，与对照组相比，高钾刺激后乙酰胆碱的细胞外释放显著缺乏。此外，通过微量注射神经示踪剂荧光金，我们发现IC和CBF之间的连接性相应受损。行为实验表明，注射到IC中的NGF抗体对条件性味觉厌恶和抑制性回避学习的获得产生了显著干扰。然而，当在注射NGF抗体之前建立条件性试验时，相同的动物能够回忆起味觉厌恶。鉴于这些结果，似乎在成年正常大脑中，皮质胆碱能功能积极依赖于局部产生的NGF，并且CBF的胆碱能活性对于回忆厌恶刺激不是必需的，但对于获得厌恶性动机的条件反射是必需的。
