Cell-type-specific regulation of neuronal intrinsic excitability by macroautophagy

eLife

Ai Yamamoto¹  Christopher J Griffey¹  Emanuela Santini²  Anders Borgkvist²  Ori J Lieberman³  Micah D Frier³  Avery F McGuirt³  David Sulzer³  Mu Yang⁴  Elizabeth Rafikian⁴ 

[1] Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, New York, United States;Department of Neuroscience, Karolinska Institute, Stockholm, Sweden;Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, United States;Mouse NeuroBehavior Core, Institute for Genomic Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, United States;

关键词: autophagy;    intrinsic excitability;    striatum;    basal ganglia;    neuronal activity;    potassium channel;   

DOI  :  10.7554/eLife.50843

来源: DOAJ

【 摘 要 】

The basal ganglia are a group of subcortical nuclei that contribute to action selection and reinforcement learning. The principal neurons of the striatum, spiny projection neurons of the direct (dSPN) and indirect (iSPN) pathways, maintain low intrinsic excitability, requiring convergent excitatory inputs to fire. Here, we examined the role of autophagy in mouse SPN physiology and animal behavior by generating conditional knockouts of Atg7 in either dSPNs or iSPNs. Loss of autophagy in either SPN population led to changes in motor learning but distinct effects on cellular physiology. dSPNs, but not iSPNs, required autophagy for normal dendritic structure and synaptic input. In contrast, iSPNs, but not dSPNs, were intrinsically hyperexcitable due to reduced function of the inwardly rectifying potassium channel, Kir2. These findings define a novel mechanism by which autophagy regulates neuronal activity: control of intrinsic excitability via the regulation of potassium channel function.

【 授权许可】

Unknown