Carrillo-Reid Luis, Tecuapetla Fatuel, Vautrelle Nicolas, Hernández Adán, Vergara Ramiro, Galarraga Elvira, Bargas José
Departamento de Biofísica, Instituto de Fisiología Celular-Neurociencias, Universidad Nacional Autónoma de México, Mexico City, Federal District 04510, Mexico.
J Neurophysiol. 2009 Aug;102(2):682-90. doi: 10.1152/jn.00134.2009. Epub 2009 May 27.
Network dynamics denoted by synchronous firing of neuronal pools rely on synaptic interactions and intrinsic properties. In striatal medium spiny neurons, N-methyl-d-aspartate (NMDA) receptor activation endows neurons with nonlinear capabilities by inducing a negative-slope conductance region (NSCR) in the current-voltage relationship. Nonlinearities underlie associative learning, procedural memory, and the sequential organization of behavior in basal ganglia nuclei. The cholinergic system modulates the function of medium spiny projection neurons through the activation of muscarinic receptors, increasing the NMDA-induced NSCR. This enhancement is reflected as a change in the NMDA-induced network dynamics, making it more synchronous. Nevertheless, little is known about the contribution of intrinsic properties that promote this activity. To investigate the mechanisms underlying the cholinergic modulation of bistable behavior in the striatum, we used whole cell and calcium-imaging techniques. A persistent sodium current modulated by muscarinic receptor activation participated in the enhancement of the NSCR and the increased network synchrony. These experiments provide evidence that persistent sodium current generates bistable behavior in striatal neurons and contributes to the regulation of synchronous network activity. The neuromodulation of bistable properties could represent a cellular and network mechanism for cholinergic actions in the striatum.
由神经元群同步放电所表示的网络动力学依赖于突触相互作用和内在特性。在纹状体中等棘状神经元中，N-甲基-D-天冬氨酸（NMDA）受体激活通过在电流-电压关系中诱导负斜率电导区域（NSCR）赋予神经元非线性能力。非线性是基底神经节核团中联想学习、程序记忆和行为顺序组织的基础。胆碱能系统通过激活毒蕈碱受体来调节中等棘状投射神经元的功能，增加NMDA诱导的NSCR。这种增强表现为NMDA诱导的网络动力学变化，使其更加同步。然而，关于促进这种活动的内在特性的贡献知之甚少。为了研究纹状体中双稳态行为的胆碱能调制的潜在机制，我们使用了全细胞和钙成像技术。由毒蕈碱受体激活调制的持续性钠电流参与了NSCR的增强和网络同步性的增加。这些实验提供了证据，表明持续性钠电流在纹状体神经元中产生双稳态行为，并有助于调节同步网络活动。双稳态特性的神经调制可能代表了纹状体中胆碱能作用的细胞和网络机制。
