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Validating Neuro-Computational Models of Neurological and Psychiatric Disorders pp 189–220Cite as

Computational Modeling of Neuronal Dysfunction at Molecular Level Validates the Role of Single Neurons in Circuit Functions in Cerebellum Granular Layer

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Part of the book series: Springer Series in Computational Neuroscience ((NEUROSCI,volume 14))

Abstract

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.

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Acknowledgments

This work derives direction and ideas from the Chancellor of Amrita University, Sri Mata Amritanandamayi Devi. SD would like to acknowledge Egidio D’Angelo and Sergio Solinas of University of Pavia, Thierry Nieus of IIT Genova and Bipin Nair, Krishnashree Achuthan, Harilal Parasuram, Chaitanya Medini, Nidheesh Melethadathil, Manjusha Nair, Asha Vijayan, Afila Yoosef, Chaitanya Kumar, Sandeep Bodda of Amrita University for their work and support in making this manuscript. This work is supported by Grants SR/CSI/49/2010, SR/CSI/60/2011 and Indo-Italy POC 2012–2014 from DST and BT/PR5142/MED/30/764/2012 from DBT, Government of India.

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  1. Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham (Amrita University), Amritapuri, 690525, Clappana P.O., Kerala, India

    Shyam Diwakar

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  1. Shyam Diwakar
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Correspondence to Shyam Diwakar .

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  1. School of Engineering, University of Lincoln, Lincoln, United Kingdom

    Basabdatta Sen Bhattacharya

  2. Office of Multidisciplinary Activities, National Science Foundation, Arlington, Virginia, USA

    Fahmida N. Chowdhury

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Diwakar, S. (2015). Computational Modeling of Neuronal Dysfunction at Molecular Level Validates the Role of Single Neurons in Circuit Functions in Cerebellum Granular Layer. In: Bhattacharya, B., Chowdhury, F. (eds) Validating Neuro-Computational Models of Neurological and Psychiatric Disorders. Springer Series in Computational Neuroscience, vol 14. Springer, Cham. https://doi.org/10.1007/978-3-319-20037-8_8

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