Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons , New York, NY, USA.
Department of Pharmacology, Columbia University Vagelos College of Physicians and Surgeons , New York, NY, USA.
Autophagy. 2020 Jun;16(6):1148-1149. doi: 10.1080/15548627.2020.1743070. Epub 2020 Mar 23.
Macroautophagy/autophagy is implicated in the maintenance of normal neuronal activity through the regulation of synaptic function and plasticity. However, differences in autophagic degradation within different classes of neurons have not been examined. We have recently demonstrated that autophagy plays very different roles in the two closely related principal neurons of the striatum - the spiny projection neurons of the direct (dSPN) and indirect (iSPN) pathways. Behavioral and electrophysiological experiments revealed that the absence of autophagy in either of these SPN pathways produces unique effects on motor learning, dendritic length, and intrinsic excitability. Specifically, autophagy is required for the normal development of synaptic inputs onto dSPNs, while being required for intrinsic excitability in iSPNs. In iSPNs, this occurs through the regulation of the activity of the KCNJ/Kir2 ion channel, and provides a first demonstration of autophagic control of neuronal intrinsic excitability.
ASD: autism spectrum disorders; dSPNs: direct pathway spiny projection neurons; iSPNs: indirect pathway spiny projection neurons; Kir2: inwardly rectifying potassium channel 2.
自噬/自噬参与通过调节突触功能和可塑性来维持正常神经元活动。然而，不同类型神经元中的自噬降解差异尚未被检测到。我们最近证明，自噬在纹状体中两种密切相关的主要神经元——直接（dSPN）和间接（iSPN）通路的棘突投射神经元中发挥着非常不同的作用。行为和电生理实验表明，这些 SPN 通路中自噬的缺失对运动学习、树突长度和内在兴奋性产生独特的影响。具体而言，自噬对于 dSPN 上突触输入的正常发育是必需的，而对于 iSPN 中的内在兴奋性是必需的。在 iSPNs 中，这是通过调节内向整流钾通道 2（KCNJ/Kir2）的活性来实现的，这首次证明了自噬对神经元内在兴奋性的控制。
ASD：自闭症谱系障碍；dSPNs：直接通路棘突投射神经元；iSPNs：间接通路棘突投射神经元；Kir2：内向整流钾通道 2。
