Chaperone-mediated autophagy controls nerve cell activity by changing synapse proteins differently in males and females

CMA deficiency leads to increased seizure susceptibility and neuronal hyperactivity in mice.

• Neuronal hyperactivity and disrupted calcium balance are associated with loss of CMA.
• Enhanced pre-synaptic neurotransmitter release and NMDA receptor activity were observed in CMA-deficient female mice.
• Males with CMA deficiency exhibited increased post-synaptic AMPA receptor activity.
• Sexual dimorphism was noted in synaptic proteins degraded by CMA, with different remodeling patterns in females and males.
• Activation of CMA in older mice improved synaptic protein levels and reduced neuronal excitability.

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