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Mesoscale simulations predict the role of synergistic cerebellar plasticity during classical eyeblink conditioning.
Geminiani, Alice; Casellato, Claudia; Boele, Henk-Jan; Pedrocchi, Alessandra; De Zeeuw, Chris I; D'Angelo, Egidio.
Affiliation
  • Geminiani A; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
  • Casellato C; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
  • Boele HJ; Digital Neuroscience Center, IRCCS Mondino Foundation, Pavia, Italy.
  • Pedrocchi A; Department of Neuroscience, Erasmus MC, Rotterdam, The Netherlands.
  • De Zeeuw CI; Neuroscience Institute, Princeton University, Washington Road, Princeton, New Jersey, United States of America.
  • D'Angelo E; NearLab, Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy.
PLoS Comput Biol ; 20(4): e1011277, 2024 Apr.
Article in En | MEDLINE | ID: mdl-38574161
ABSTRACT
According to the motor learning theory by Albus and Ito, synaptic depression at the parallel fibre to Purkinje cells synapse (pf-PC) is the main substrate responsible for learning sensorimotor contingencies under climbing fibre control. However, recent experimental evidence challenges this relatively monopolistic view of cerebellar learning. Bidirectional plasticity appears crucial for learning, in which different microzones can undergo opposite changes of synaptic strength (e.g. downbound microzones-more likely depression, upbound microzones-more likely potentiation), and multiple forms of plasticity have been identified, distributed over different cerebellar circuit synapses. Here, we have simulated classical eyeblink conditioning (CEBC) using an advanced spiking cerebellar model embedding downbound and upbound modules that are subject to multiple plasticity rules. Simulations indicate that synaptic plasticity regulates the cascade of precise spiking patterns spreading throughout the cerebellar cortex and cerebellar nuclei. CEBC was supported by plasticity at the pf-PC synapses as well as at the synapses of the molecular layer interneurons (MLIs), but only the combined switch-off of both sites of plasticity compromised learning significantly. By differentially engaging climbing fibre information and related forms of synaptic plasticity, both microzones contributed to generate a well-timed conditioned response, but it was the downbound module that played the major role in this process. The outcomes of our simulations closely align with the behavioural and electrophysiological phenotypes of mutant mice suffering from cell-specific mutations that affect processing of their PC and/or MLI synapses. Our data highlight that a synergy of bidirectional plasticity rules distributed across the cerebellum can facilitate finetuning of adaptive associative behaviours at a high spatiotemporal resolution.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Computer Simulation / Cerebellum / Conditioning, Eyelid / Models, Neurological / Neuronal Plasticity Limits: Animals Language: En Journal: PLoS Comput Biol Journal subject: BIOLOGIA / INFORMATICA MEDICA Year: 2024 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Computer Simulation / Cerebellum / Conditioning, Eyelid / Models, Neurological / Neuronal Plasticity Limits: Animals Language: En Journal: PLoS Comput Biol Journal subject: BIOLOGIA / INFORMATICA MEDICA Year: 2024 Document type: Article Affiliation country: Country of publication: