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Brain mitochondria as key drivers of cognition and behaviour.

Created on 14 Jul 2026

Authors

Carmen Sandi, Mary Kay Lobo, Fiona Hollis, Yusuke Hirabayashi, Jaime de Juan-Sanz, Juan P Bolaños

Published in

Nature reviews. Neuroscience. Jul 13, 2026. Epub Jul 13, 2026.

Abstract

Cognition and behaviour arise from computations in neural circuits, which can differ in their readiness for recruitment or in the computations and behavioural outputs that they generate. Mitochondria contribute to both circuit properties and their variability by shaping the cellular processes on which circuit function depends. Across neurons and glia, mitochondria provide bioenergetic support, regulate Ca2+ dynamics and reactive oxygen species levels, influence neurotransmitter synthesis and turnover, and sustain quality control programmes that preserve cellular integrity. The capacity of mitochondria to provide this support and their plasticity have been linked to circuit architecture, engagement and adaptation, with implications for learning and memory, reward and reinforcement, state-trait anxiety and motivation. Here we describe two complementary modes of mitochondrial support: a baseline mode, in which mitochondria sustain circuit architecture and physiological properties over long timescales, and an activity-evoked mode, in which local mitochondrial outputs support synaptic transmission and plasticity. Distinguishing these two modes helps to explain how behavioural modulators, including stress hormones, immune activity and metabolic signals, can shape behaviour by altering either baseline mitochondrial control of circuit readiness or activity-evoked mitochondrial support during circuit engagement.

PMID:
42443461
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

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