Using mathematical modelling, we attempted to reconstruct the information transmission at the granular layer of the cerebellum, a circuit whose functions and dysfunctions remain yet to be explored in detail. Information transmission at the Mossy Fiber (MF)—Granule cell (GrC) synaptic relay is crucial to understand mechanisms of signal coding in the cerebellum and related impacts of connectivity mechanisms. Using biophysically detailed multi-compartmental models, simple spiking neurons we reconstructed granular layer micro-circuitry and estimated both single neuron behaviour and network activity in terms of center-surround patterns, as observed during sensory and tactile stimulation. The chapter also includes local field potential reconstructions to show plasticity mechanisms at the molecular level is reflected at the network activity level, indicating network LFP in the granular layer is a regulated activity signal arising from the underlying granule cells and the feed-forward inhibition from the Golgi cells. The role of selective inhibition by Golgi cells for coincidence detection is presented. Exploring the EPSP-spike complex in granular neurons revealed potential mechanisms for sparse recoding in cerebellum and quantification of information encoding in individual neurons of the cerebellar granular layer. We also look into two specific forms of neuronal dysfunction with ataxia-like behaviour in knockout mice models and in NMDAR-related autism. While network activity was severely affected, the amplitude of damage is critical of the mechanisms at the cellular or molecular level. The study further enhances our understanding of specific coding geometries in the cerebellum and spatio-temporal processing in a primary circuit of the cerebellum.
Dr. Shyam Diwakar, “Computational Modeling of Neuronal Dysfunction at Molecular Level Validates the Role of Single Neurons in Circuit Functions in Cerebellum Granular Layer”, in Validating Neuro-Computational Models of Neurological and Psychiatric Disorders, Springer, 2015, pp. 189–220.