IGF-1 receptor regulates upward firing rate homeostasis via the mitochondrial calcium uniporter.

ABSTRACT: Regulation of firing rate homeostasis constitutes a fundamental property of central neural circuits. While intracellular Ca²⁺ has long been hypothesized to be a feedback control signal, the molecular machinery enabling a network-wide homeostatic response remains largely unknown. We show that deletion of insulin-like growth factor-1 receptor (IGF-1R) limits firing rate homeostasis in response to inactivity, without altering the distribution of baseline firing rates. The deficient firing rate homeostatic response was due to disruption of both postsynaptic and intrinsic plasticity. At the cellular level, we detected a fraction of IGF-1Rs in mitochondria, colocalized with the mitochondrial calcium uniporter complex (MCUc). IGF-1R deletion suppressed transcription of the MCUc members

SUBMITTER: Katsenelson M 

PROVIDER: S-EPMC9388073 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature