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Homeostatic bidirectional plasticity in upbound and downbound micromodules in a model of the olivocerebellar loop

Onderzoeksgroep De Zeeuw
Publicatiejaar 2025
Gepubliceerd in PLoS Computational Biology
Auteur(s) Elías M Fernández Santoro, Lennart P L Landsmeer, Said Hamdioui, Christos Strydis, Chris I De Zeeuw, Aleksandra Badura, Mario Negrello

Olivocerebellar learning is highly adaptable, unfolding over minutes to weeks depending on the task. However, the stabilizing mechanisms of the synaptic dynamics necessary for ongoing learning remain unclear. We constructed a model to examine plasticity dynamics under stochastic input and investigate the impact of inferior olive (IO) reverberations on Purkinje cell (PCs) activity and synaptic plasticity. We explored Upbound and Downbound cerebellar micromodules, which are organized loops of IO neurons, cerebellar nuclei neurons and microzones of PCs characterized by their unique molecular profiles and different levels of baseline firing. Our findings show synaptic weight convergence followed by stability of synaptic weights. In line with their relatively low and high intrinsic firing, we observed that Upbound and Downbound PCs have a propensity for potentiation and depression, respectively, with both PC types reaching stability at differential levels of overall strength of their parallel-fiber (PF) inputs. The oscillations and coupling of IO neurons participating in the Upbound and Downbound modules determine at which frequency band PFs can be stabilized optimally. Our results indicate that specific frequency components drive IO resonance and synchronicity, which, in turn, regulate temporal patterning across Upbound and Downbound zones, orchestrating their plasticity dynamics.

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