Devine, Michael J;
Szulc, Blanka R;
Howden, Jack H;
López-Doménech, Guillermo;
Ruiz, Arnaud;
Kittler, Josef T;
(2022)
Mitochondrial Ca²⁺ Uniporter haploinsufficiency enhances long-term potentiation at hippocampal mossy fibre synapses.
Journal of Cell Science
10.1242/jcs.259823.
(In press).
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Abstract
Long-term changes in synaptic strength form the basis of learning and memory. These changes rely upon energy demanding mechanisms which are regulated by local Ca2+ signaling. Mitochondria are optimised for providing energy and buffering Ca2+. However, our understanding of the role of mitochondria in regulating synaptic plasticity is incomplete. Here we have used optical and electrophysiological techniques in cultured hippocampal neurons and ex vivo hippocampal slices from mice with haploinsufficiency of the mitochondrial Ca2+ uniporter (MCU+/-) to address whether reducing mitochondrial Ca2+ uptake alters synaptic transmission and plasticity. We found that cultured MCU+/- hippocampal neurons have impaired Ca2+ clearance, and consequently enhanced synaptic vesicle fusion at presynapses occupied by mitochondria. Furthermore, long-term potentiation (LTP) at mossy fibre (MF) synapses, a process which is dependent on presynaptic Ca2+ accumulation, is enhanced in MCU+/- slices. Our results reveal a previously unrecognized role for mitochondria in regulating presynaptic plasticity of a major excitatory pathway involved in learning and memory.
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