Cell-type-specific regulation of neuronal intrinsic excitability by macroautophagy
Year: 2020
Type: article
Abstract: 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.
Source: eLife
DOI: 10.7554/elife.50843
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: G1833045553, STRIATAL SPECIFIC ALTERATIONS IN TRANSLATION, SYNAPTIC FUNCTION, AND BEHAVIOR IN, Regulation of striatal maturation by dopamine and macroautophagy: implications for neuropsychiatric disorders, G3027588297, Selective autophagy in Parkinson'sdisease, G3418609617, G3883639062, G5197149029, Medical Scientist Training Program, G8761209232
OpenAlex ID: W2999517587