P030 Synaptic Plasticity Mechanisms and Dynamics in the Cerebellar Spiking Microcircuit
Abdul H Butt*1, Marialaura De Grazia1, Emiliano Buttarazzi1 , Dimitri Rodarie1, Claudia Casellato1, D' Angelo Egidio1 1Department of Brain and Behavioural Science, University of Pavia, Pavia, Italy
*Email: abdulhaleembutt85@gmail.com
Introduction
Short-term plasticity (STP) is crucial for regulating excitatory and inhibitory information flow in the cerebellar cortex by modulating synaptic efficiency over seconds to minutes, acting as a dynamic filter for information processing. It shapes synaptic activity, alongside long-term plasticity (LTP) that arises from sustained stimulation. Both firing rates and spike timing affect plasticity, with distinct mechanisms across brain regions. This study introduces the Tsodyks-Markram STP model in cerebellar circuits reconstructed with detailed structural properties, and aims to integrate STP and LTP to explore their combined effects on cerebellar dynamics [1, 2].
Methods The canonical cerebellar circuit, reconstructed and simulated as a point neuron network using Brain Scaffold Builder (BSB) interfaced with NEST [3,4], has been enhanced by incorporating short-term plasticity (STP) [1,2]. This involved adjusting the utilization parametersU, u, x, τ_fac, and τ_recto ensure proper facilitation and depression. The synaptic models were tested in both in-vitro and awakecanonical models of the mouse olivocerebellar microcircuit, focusing on both baseline firing rates and responses under specific stimulation protocols inspired from Pavlovian paradigms a input at mossy fibers (mf) at 40 Hz within the time window [1000–1260] ms and an impulse on the climbing fibers originating from the inferior olive (IO) as a 500 Hz burst within the time interval [1250–1260] [5].
Results The single-cell pipeline confirmed that facilitation and depression function as expected. At high-frequency stimulation, facilitation prevails at the Glomeruli-Granule (Glom-GrC) synapses (Fig. 1A). The same phenomenon was investigated throughout the canonical circuit for each connection.Mean firing rates of each population show (Fig.1B-C) that STP plays a crucial role in the modulation of neuronal activity within the cerebellar cortical model. Purkinje cells (PCs) exhibit increased firing rates with STP, suggesting facilitation enhances their excitability.Basket cells and Deep Cerebellar Nuclei neurons (DCN, both _P (projecting) and _I (inhibitory)) exhibit reduced firing rates when STP is present, indicating synaptic depression reduces activity over time. Also the Inferior Olive neurons (IO) show a significant increase in their mean firing rate of IO stimulus when introducing STP.
Discussion The results show the significant impact of STP in terms of signal propagation. Future work will explore the combination of STP-LTP which operate on two diffeent time scales and their interactions in sensorimotor loops during motor learning protocols [6, 7]. Specifically, LTP plasticity rules have been introducedon synapses at parallel fibers to Purkinje cells and parallel fibers to Molecular Layer Interneurons [6], utilizing awake version of the canonical cerebellar circuit.
Figure 1. Figure 1 A) Single-synapse STP dynamics, B) Canonical circuit in-vitro and awake (with STP vs static), response at step-like mf stimulus. C) Raster plot of the awake circuit (with STP vs static) with mf-IO stimulus paradigm Acknowledgements ·The European Union’s Horizon Europe Programme under the Specific Grant Agreement No. 101147319 (EBRAINS 2.0 Project)
·“National Centre for HPC, Big Data and Quantum Computing” (Project CN00000013 PNRR MUR – M4C2 – Fund 1.4 - Call “National Centers” - law decree n. 3138 16 december 2021) References ● https://doi.org/10.1073/pnas.94.2.719 ● https://doi.org/10.1152/jn.00258.2001 ● https://doi.org/10.1038/s42003-022-04213-y ● https://doi.org/10.5281/zenodo.7243999 ● https://doi.org/10.1371/journal.pcbi.1011277 ● https://doi.org/10.1109/TBME.2015.2485301 ● https://doi.org/10.1371/journal.pcbi.1008265
