An integrative study of neural coding in the vestibular cerebellum: from cellular physiology to models of network behaviour

Lead Research Organisation: University College London
Department Name: Physiology


We form representations of our surroundings using our primary senses: seeing, hearing, smelling, tasting and touching the world around us. To process this vast array of information brains have evolved specialized regions dedicated to specific types of sensory modalities. In mammals including humans we know when this information reaches the brain it is placed in context through multimodal integration within and between these different regions. The success of this kind of integration is highlighted, for example, by our ability to compute the location of an auditory or visual stimulus relative to head position. Vestibular information, the so-called sixth sense has perhaps the most dramatic and yet underappreciated influence throughout the central nervous system, contributing to functions such as vision, hearing, movement, cognition, sleep, digestion and even learning and memory. More specifically it is presumed to underlie an internal gravity model in humans as well as an intrinsic spatial coordinate system. Defects of the vestibular system result in impaired spatial perception and memory as well as failure to perceive self-motion. In fact disequilibrium affects almost half of the population by age 60 and is as prevalent as hypertension and angina. Recent clinical studies have reported that isolated cortical lesions in humans can cause recurrent episodes of vertigo and imbalance that are consistent with extracellular electrophysiological studies in primates and cats showing vestibular contributions to cortical activity. In this project we will elucidate the neural mechanisms of vestibular representation in the cerebellum- the primary structure know to be involved in maintaining balance, posture and the control of movement. We will combine cellular studies in brain slices that allow us to examine the microscopic mechanisms involved in regulating single cell excitability with a systems approach that uses natural stimulation in the intact animal. Computer simulations will allow us to explore the mechanisms of vestibular signalling on the large scale that the cerebellum is known to operate on. Findings from this provide an understanding of the neural basis of balance and movement and shed light on the underlying causes of disequilibrium and vertigo.

Technical Summary

Organised as networks of interconnected modules, cortices are the parallel distributed processors of the brain. We propose here to take a systems biology approach to breaking the cerebellar code, that is to use the power of systems neuroscience, computation and modelling to infer the properties of the cerebellar microcircuit from the properties of its parts. To reach this goal our consortium includes cellular neurophysiologists with a long-lasting interest in cerebellar microcircuits, in vivo electrophysiologists, specialists of neuronal computing and of statistical physics. By bringing together scientists with this broad spectrum of competence, we aim at developing an explicit model of the cerebellar cortex that will be tightly constrained by detailed morphological and physiological data. Because its anatomically well-defined and natural sensory stimuli (ie in the input stimuli) are readily quantifiable we will focus on signal processing in the vestibular cerebellum. To address this question we record intracellularly from cerebellar mossy fibers (input), uniploar brush cells (UBCs) and granule cells (GCs) in vivo during vestibular stimulation. We will then use analysis methods derived from information theory to quantify the amount of information that is transferred to GCs. We will then analyse and model information transfer synapse by synapse in vitro to understand how UBCs and GCs might integrate mossy fibers inputs. These data will serve to construct an explicit model of the granular layer in 3D using neuroConstruct. We will then use an in vitro model of triggered activity to constrain computer modelling by comparing patterns of activity evoked single cell activation in silico and in the slice. Gradually additional components of network processing such as inhibition and transmitter spillover will be added to generate a comprehensive model of vestibular cerebellum computation.
Description In this project we studied one of the simplest cortical brain areas: the cerebellum. We studied how sensory information about head position and movement is processed, allowing us to maintain posture and balance. To do this we combined experiments with sophisticated computer models of networks of neurons. The scientific discoveries in this project have lead to a better understanding of how the brain represents sensory information, and how networks of neurons coordinate their electrical activity.
Exploitation Route Understanding how information about the body and the surrounding world is represented in electrical signals flowing through complex networks of neurons in the brain, is one of the most exciting and challenging problems in science. This project provided a number of fundamental new insights into information processing in the brain. This knowledge provides a foundation of basic knowledge and concepts with which to understand what goes wrong during neurological disorders.
Sectors Education,Healthcare,Pharmaceuticals and Medical Biotechnology

Description The aim of this award was to increase our understanding of how synapses, neurons and networks represent and process information. The main outcomes are therefore scientific discoveries that extend our knowledges of brain function. Although, at present, they do not have direct application outside neuroscience research they revealed several fundamental properties that are likely to be important for understanding network dysfunction during neurological disorders and disease states. Also, by improving standardization and the tools for modelling brain function this work is also contributing to future research in this area.
First Year Of Impact 2011
Sector Digital/Communication/Information Technologies (including Software),Education,Healthcare,Pharmaceuticals and Medical Biotechnology,Other
Impact Types Cultural

Description Wellcome Trust Biomedical resources Award (Development and standardization of biologically realistic neural network models through an open source database)
Amount £1,048,732 (GBP)
Funding ID 086699 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2008 
End 11/2013
Description Wellcome Trust Principal Research Fellowship
Amount £2,700,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2011 
End 08/2016
Title NeuroML: a language for describing data driven models of neurons and networks 
Description Biologically detailed single neuron and network models are important for understanding how ion channels, synapses and anatomical connectivity underlie the complex electrical behavior of the brain. NeuroML ( is an XML based language for specifying data driven models of neurons and networks with a high degree of biological detail. NeuroML facilitates the exchange of complex neural models across specialist simulators, allowing greater transparency, validation and accessibility of models. There are a growing number of applications with support for NeuroML. 
Type Of Material Technology assay or reagent 
Year Produced 2010 
Provided To Others? Yes  
Impact NeuroML is an international collaborative effort that has been recognized by the INCF as a potential standard for computational neuroscience. We have built a website for this open source project, which provides information and validation tools for this initiative. The development of NeuroML is actively ongoing. The first version of NeuroML can be used to define and store a wide range of existing computational neuroscience models. We are also currently working with simulator developers to make their software NeuroML complaint. 
Description Determinants of information processing in Cerebellum 
Organisation Hungarian Academy of Sciences (MTA)
Department Institute of Experimental Medicine
Country Hungary 
Sector Academic/University 
PI Contribution Provide electrophysiology, imaging and modelling to the project.
Collaborator Contribution Contibute quantitative anatomical studies.
Impact Rapid desynchronization of an electrically coupled interneuron network with sparse excitatory synaptic input. Neuron. 2010 Aug 12;67(3):435-51. Gap junctions compensate for sublinear dendritic integration in an inhibitory network. Science. 2012 Mar 30;335(6076):1624-8.
Start Year 2006
Description Development of NeuroML 
Organisation Arizona State University
Country United States 
Sector Academic/University 
PI Contribution We have been the main contributor and developer of the NeuroML initiative.
Collaborator Contribution The Crook Lab collaborates with my Lab on the open source NeuroML project (, which is developing a model description language for single neuron and network models in computational neuroscience.
Impact A description of the part of NeuoML that deals with neuronal morphologies was published in 2007 (Pubmed ID 17873371). A website describing this initiative, together with software tools is available at ( NeuroML: a language for describing data driven models of neurons and networks with a high degree of biological detail. PLoS Comput Biol. 2010 Jun 17;6(6):e1000815.
Start Year 2006
Description Role of NMDARs in information transmission 
Organisation École Normale Supérieure, Paris
Country France 
Sector Academic/University 
PI Contribution We helped design experiments and performed mathematical modelling for a collaborative study examining the role of NMDARs in information transmission trough the input layer of the cerebellar cortex.
Collaborator Contribution Our partners at Ecole Normale Superieure Initiated the project and carried our experiments .
Impact NMDA receptors with incomplete Mg²? block enable low-frequency transmission through the cerebellar cortex. Schwartz EJ, Rothman JS, Dugué GP, Diana M, Rousseau C, Silver RA, Dieudonné S. J Neurosci. 2012 May 16;32(20):6878-93. doi: 10.1523/JNEUROSCI.5736-11.2012.
Start Year 2010