Sensory processing in single cells, circuits and behaviour

Lead Research Organisation: MRC National Inst for Medical Research

Abstract

The brain has evolved to detect and process sensory information to produce appropriate behavioural outputs. To achieve this, the incoming sensory information must be placed in context. For example, the location of a sound or odor source can only be ascertained if the brain has an internal representation of the direction of the head in space, a process that relies on the coding properties of individual neurons and neuronal circuits. We are therefore investigating several aspects of the cellular and network mechanisms underlying sensory computation. In the olfactory bulb, a region of brain that processes odor information, we will determine whether the transmission of signals between specific subsets of connected cells influences a neurons intrinsic physiological and coding properties. Secondly, by recording large-scale network activity in the intact animal during rotation we are investigating how large populations of interconnected neurons use information from the vestibular system to encode the velocity and the direction of body motion.

Technical Summary

Knowing how the brain processes sensory information and performs the computations required for perception, cognition and memory is central to understanding its function during health and disease. In many brain regions, sensory stimulation evokes distributed activity across local and long-range networks. In some cases this activity can be confined to a particular region dedicated to processing a particular sense, but it can also often be distributed over multiple areas reflecting multi-modal higher order processes. Our program of work focuses on understanding how individual synaptic inputs, single cells and collections of neurons process sensory information. To achieve this we use in vitro electrophysiology together with in vivo electrophysiology and genetic tracing, two-photon imaging and behaviour. This allows us to explore the fundamental synaptic and cellular mechanisms of sensory processing while probing, at the systems level, the interplay between single cell computation and the functional dynamics and connectivity of neuronal networks. Our program of work falls along two complimentary themes that investigate the cellular and network mechanisms of representation of two modalites, the olfactory and vestibular senses that offer unique advantages. In the olfactory bulb, where functional networks can be visually identified, we ask two questions: are the biophysical properties of individual cells influenced by the neuronal networks they comprise and secondly, to what extent does sensory experience impact such properties? The second research program takes advantage of the quantitative nature of vestibular stimuli that can be used to explore a relatively large and defined region of sensory stimulus space. We are currently investigating the synaptic mechanisms of vestibular representation in the cerebellar granule cell where we can resolve the contribution of individdual synaptic inputs. In this model cell type we are determining the balance of vestibular-evoked synaptic excitation and inhibition and whether or not such signals are integrated with synaptic events arising from other, functionally distinct inputs. Thus at the single cell level, the fundamental synaptic mechanisms underlying sensory signalling are being determined. We also propose to explore vestibular sensory processing at the level of cortical networks. By targeting regions such as secondary visual cortex where our recent data indicate integration of vestibular information is likely to occur, we are undertaking experiments designed to understand sensory representation in the context of multi-modal processing. We are also investigating the relationsip between the function of an individual cortical cell and its connectivity within the network.

Publications

10 25 50
 
Description The function and connectivity of single cells and circuits
Amount £2,300,000 (GBP)
Funding ID 096436/B/11/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2012 
End 12/2018
 
Description Vestibular representation in the cerebellum
Amount £250,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2008 
End 12/2010
 
Title Novel method for single cell transfection in vivo 
Description Method enabling combined electrophysiological characterisation and genetic manipulation of single cells in vivo. 
Type Of Material Database/Collection of Data/Biological Samples 
Provided To Others? No  
Impact It provides read out of cell function and connectivity. 
 
Description The function and connectivity of cortical cells and circuits 
Organisation Cold Spring Harbor Laboratory (CSHL)
Country United States 
Sector Charity/Non Profit 
PI Contribution -
Collaborator Contribution -
Impact -
Start Year 2012
 
Description Viral Tracing of Neuronal Connectivity 
Organisation Columbia University Medical Center
Department Department of Neuroscience
Country United States 
Sector Academic/University 
PI Contribution Our collaborators co-designed viral and DNA constructs so that we may attempt to deliver DNA into single cells during electrophysiological recording in vivo. We executed all of the chronic recordings and performed all of the tracing here at NIMR.
Collaborator Contribution Provided us with research tools and disseminated information to assist in the ongoing development of such tools.
Impact Published manuscript. Title: Transfection via whole-cell recording in vivo: bridging single-cell physiology, genetics and connectomics Author(s): Rancz Ede A.; Franks Kevin M.; Schwarz Martin K.; et al. Source: NATURE NEUROSCIENCE Volume: 14 Issue: 4 Pages: 527-U169 DOI: 10.1038/nn.2765 Published: APR 2011
Start Year 2009
 
Description School Student Visit to Institute 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Primary Audience Schools
Results and Impact 50 students attended research talks.

School asked for lab visit for specific students to write essay on topics that interest them
Year(s) Of Engagement Activity 2009,2010