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bioRxiv · 10.1101/2021.04.30.442089

mir124-dependent tagging of glutamatergic synapses by synaptopodin controls non-uniform and input-specific homeostatic synaptic plasticity

Dubes, S.·Soula, A.·Benquet, S.·Tessier, B.·Poujol, C.·Favereaux, A.·Thoumine, O.·Letellier, M.
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Abstract

Homeostatic synaptic plasticity (HSP) is a process by which neurons adjust synaptic strengths to compensate for various perturbations and which allows to stabilize neuronal activity. Yet, whether the highly diverse synapses harboring a neuron respond uniformly to a same perturbation is unclear and the underlying molecular determinants remain to be identified. Here, using patch-clamp recordings, immunolabeling and imaging approaches, we report that the ability of individual synapses to undergo HSP in response to activity-deprivation paradigms depends on the local expression of the spine apparatus related protein synaptopodin (SP) acting as a synaptic tag to promote AMPA receptor synaptic accumulation and spine growth. Gain and loss-of-function experiments indicate that this process relies on the local de-repression of SP translation by miR124 which supports both non-uniform and synapse-autonomous HSP induced by global or inputspecific activity deprivation, respectively. Our findings uncover an unexpected synaptic-tagging mechanism for HSP, whose molecular actors are intriguingly shared with Hebbian plasticity and linked to multiple neurological diseases.

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Dubes, S., Soula, A., Benquet, S., Tessier, B., Poujol, C., Favereaux, A., Thoumine, O., Letellier, M.. 2021-04-30. mir124-dependent tagging of glutamatergic synapses by synaptopodin controls non-uniform and input-specific homeostatic synaptic plasticity. https://doi.org/10.1101/2021.04.30.442089

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