Study of hippocampal cell-ensembles and circuits during behaviour

Lead Research Organisation: MRC Anatomical Neuropharmacology Unit

Abstract

The hippocampus is a brain region which is involved in learning, memory and spatial navigation. It is also associated with certain mental diseases such as temporal lobe epilepsy and memory disorders. The anatomical structure of hippocampal circuits and the activity patterns of the neurons of which they are composed are well described. However, it is not yet understood how groups of neurons work together to contribute to behaviour, nor how disturbances in neuronal collaboration may contribute to mental diseases.||The proposed research programme aims to define the activity patterns of different types of hippocampal neurons during both waking activity and sleep. The goal is to decipher how these neurons work together to guide behaviour and to consolidate momentary experiences into long-term memory.||This work will increase our understanding of the function of the hippocampus and explain how behaviour-dependent neuronal activity is generated. A detailed understanding of hippocampal circuits is essential for relating their role in normal brain function, and for the treatment of mental diseases.

Technical Summary

The hippocampus is a cortical structure, which is involved in wide variety of functions, including spatial navigation and the encoding and consolidation of declarative/semantic memories. It is also associated with mental diseases such as temporal lobe epilepsy and certain memory disorders. The anatomy of hippocampal circuits is well described and there is a growing body of data concerning the physiological properties of hippocampal neurons. However, it is not yet understood how the collaborative responses of neurons in hippocampal circuits contribute to behaviour, nor how disturbances in circuit operations may contribute to mental disorders.||The aim of the research programme is to reveal how the cooperative activity of neuronal assemblies contributes to hippocampal function and whole-animal behaviour. The main objectives are (i) to define the network mechanisms contributing to the replay of waking activity patterns during sleep - a phenomenon associated with memory consolidation processes. (ii) to establish the mechanism and behavioural role of population patterns such as network oscillations (e.g. theta or gamma oscillations) and network burst patterns (e.g. sharp waves, dentate spikes). (iii) to determine some of the rules and underling mechanism of how the hippocampal representation of space (cognitive maps) are formed and maintained during spatial exploratory behaviour.||All these tasks require monitoring the simultaneous activity of many neurons from different hippocampal sub-circuits. To this end, we use multi-channel extracellular recording techniques in freely moving rats. Multi-site silicon microelectrodes and independently movable multi-site microelectrode arrays (e.g. tetrodes) are used to record neuronal activity during spatial exploration tasks and during sleep. Principal cells and different interneuron types are discriminated based on criteria that have been developed using dual intra and extracellular or juxtacellular recordings in acute in vivo recordings.||This work aims to increase our understanding of the function of hippocampal circuits and explain how behaviour-dependent neuronal responses emerge in these circuits. Such detailed investigation of hippocampal circuits and the resultant advances in the understanding of their function are essential to the development of novel strategies for treating mental diseases. For example, the functional definition of hippocampal circuits and their roles in memory consolidation may result in new ways to treat diseases that cause memory deficits.

Publications

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Description Schizophr Bull. 2008 Sep;34(5):974-80 PMID: 18559405
Geographic Reach National 
Policy Influence Type Citation in clinical reviews
Impact This review highlights for clinicians the role of oscillations in Schizophrenia, and the possible implication of my work in it.
URL http://europepmc.org/abstract/MED/18559405
 
Title Spike clustering 
Description I tool to differentiate the activity of different cells in extracellular multichannel recordings 
Type Of Material Data analysis technique 
Year Produced 2006 
Provided To Others? Yes  
Impact It enables the study of population of neurons during behaviour in the brain 
 
Title Spike data 
Description We have collected data and assembled a large database in which the activity of hippocampal CA1 neurons (pyramidal cells and interneurons) was recorded both in behaviour and anaesthesia. This work forms the D.Phil. thesis of one of my students. The database is not public yet as we have not published it. 
Type Of Material Database/Collection of Data/Biological Samples 
Provided To Others? No  
Impact We have collected data and assembled a large database in which the activity of hippocampal CA1 neurons (pyramidal cells and interneurons) was recorded both in behaviour and anaesthesia. This work forms the D.Phil. thesis of one of my students. The database has not released in public databases yet as we have not published it. 
 
Description Dedritic spike patterns using real data 
Organisation University of Bonn
Country Germany 
Sector Academic/University 
PI Contribution Provided spike data to test how action potetials propagate to dendrites of in vitro cells.
Collaborator Contribution Paper in Neuron
Impact PMID: 19323999
Start Year 2008
 
Description Open Day for local schools 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Primary Audience Schools
Results and Impact Several local schools have visitted the unit and learnt about research here.

Several letter of feedback from schools
Year(s) Of Engagement Activity 2006,2007,2008