Autophagy is dispensable for the maintenance of parvalbumin interneurons but required for their inhibitory neurotransmission and memory

ABSTRACT: Previous studies have demonstrated the requirement of autophagy for neuronal survival and synaptic function, mostly focusing on projection neurons and excitatory neurotransmission. Here, we examine the effects of conditional atg5 ablation in neurons expressing parvalbumin (PV-cKO), which in the forebrain mainly represent fast-spiking inhibitory interneurons. Contrary to the prevailing view, we show that autophagy-deficient PV neurons survive throughout the brain, with the exception of the projection Purkinje neurons in the cerebellum, which rapidly degenerate. While not affecting their maintenance, autophagy deficiency leads to aberrant proteostasis of key synaptic and other proteins, culminating to reduced inhibitory neurotransmission in hippocampal PV-interneurons. Consistently, PV-cKO animals exhibit associative and recognition memory deficits. Our findings demonstrate a neuronal type-specific vulnerability to autophagy deficiency, while also identifying PV-interneurons as the cellular substrates where autophagy is required for memory formation.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Patrice Waridel  

LAB HEAD: Vassiliki Nikoletopoulou

PROVIDER: PXD035264 | Pride | 2026-02-02

REPOSITORIES: Pride