Hippocampal, Subcortical and Cortical Interactions in Memory and Plasticity

Lead Research Organisation: University of Edinburgh
Department Name: Biomedical Sciences

Abstract

There is enormous public interest in brain function and dysfunction. What factors determine how our brains develop? What do the different parts of the brain do? How do they work? Does it matter what we eat? What is the value and what are the risks of taking certain types of potentially addictive drugs? Interest in neuroscience has never been greater and, in particular, understanding more about how memory works is high on the list of topics that attracts public attention.

The neurobiological theory that we seek to evaluate in this programme of research has psychological, neurobiological, and molecular-genetic strands to it. These include the further development of novel tests of memory in animals, physiological studies of brain activity involved in making, storing, and retrieving memories, and work with genetically altered mice expressly engineered to mimic key aspects of Alzheimer?s Disease. Each of the applicants has had occasion to explain some of the ideas in public lectures or schools visits. These have provided opportunities to talk about the principles of multiple memory systems, of the distinct brain areas involved, of the importance of synaptic growth and change, and of the way that drugs can affect memory. We try to put these ideas across in a way that conveys the central concepts in a straightforward manner, while respecting the true complexity of the underlying science. One of us (RGMM) is President of FENS and a Council Member of the European Dana Alliance (EDAB). He has recently coordinated the revision of the British Neuroscience Association?s booklet on ?Neuroscience: the Science of the Brain? that has been distributed gratis to all secondary school science departments in the UK and, through BNA and IBRO, is translated into several languages (including Spanish and Mandarin).

We also recognise that the therapeutics aspect of our research much be treated with caution. We are privileged to be making a small contribution to what we hope could yet become a preventive treatment for Alzheimer?s Disease. However, such work should be reported to the public with great care for fear of raising hopes falsely, and well beyond what the current level of animal models of the disease can justify.

We are committed to the public communication of science in an informed but responsible manner.

Technical Summary

Understanding memory and memory dysfunction is a major goal of neuroscience. This programme of research, divided into four projects, tests a hypothesis about the neurobiology of memory with studies of hippocampal, subcortical and cortical interactions in encoding, consolidation and storage. Project 1 focuses on searching for the neural signatures of paired-associate encoding using a novel behavioural paradigm. Project 2 concerns cellular consolidation, focusing on the concept of synaptic tagging and its importance in protein synthesis-dependent long-term potentiation with research on signal transduction pathways relevant to tag-setting and plasticity proteins. Project 3 follows up exciting new work on schema learning and its relevance for systems-level consolidation using immediate early gene mapping. Project 4 builds on the other three projects by bringing modern concepts of the neuroscience of learning and memory to bear on the pressing problem of testing novel therapeutics for neurodegenerative diseases.

Publications

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Redondo RL (2010) Synaptic tagging and capture: differential role of distinct calcium/calmodulin kinases in protein synthesis-dependent long-term potentiation. in The Journal of neuroscience : the official journal of the Society for Neuroscience

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Yehuda R (2010) The memory paradox. in Nature reviews. Neuroscience

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Bethus I (2010) Dopamine and memory: modulation of the persistence of memory for novel hippocampal NMDA receptor-dependent paired associates. in The Journal of neuroscience : the official journal of the Society for Neuroscience

 
Description Caledonian Research Foundation
Amount £154,691 (GBP)
Organisation University of Edinburgh 
Department Caledonian Research Foundation
Sector Academic/University
Country United Kingdom
Start 01/2011 
End 04/2014
 
Description European Research Council
Amount £3,150,000 (GBP)
Funding ID 268800 
Organisation European Research Council (ERC) 
Sector Public
Country European Union (EU)
Start 06/2011 
End 05/2016
 
Description Mitsubishi Tanabe Pharmaceutical Company
Amount £127,000 (GBP)
Organisation Mitsubishi Tanabe Pharma Corporation 
Sector Private
Country Japan
Start 04/2010 
End 02/2012
 
Title Temperature controller for brain slice physiology 
Description We have developed temperature controller software that will monitor and control the full electrophysiology rig and provide the capability to run acute-slice experiments overnight. In a brain slice chamber the conventional heater can cause droplets of condensation from the fluid filled chamber to form on the cooler electrodes and consequently limit the time available to collect brain slice recording. Rather than controlling the heating of the slice chamber, the temperature software controller maintains the temperature of everything within the insulated rig. The temperature of the oxygenated air, the brain slice, the electrodes and the remaining rig equalise providing a stable environment for long-term recordings. Example: the temperature can be maintained at a constant 32 degrees and extend the length of slice viability to times that allow investigations of long-term changes in synaptic connectivity. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2010 
Provided To Others? Yes  
Impact Assisted with research projects 
 
Description GRIDMAP 
Organisation Norwegian University of Science and Technology (NTNU)
Department Medical Technical Institute; Norwegian Technical University of Trondheim
Country Norway 
Sector Academic/University 
PI Contribution Conducting joint experiments (from 2013 onwards)
Collaborator Contribution Conducting joint experiments (from 2013 onwards)
Impact None yet, grant received but not yet activated.
Start Year 2012
 
Description NEUROSCHEMA 
Organisation Radboud University Nijmegen
Department Donders Institute for Brain, Cognition and Behaviour
Country Netherlands 
Sector Academic/University 
PI Contribution Prepared major grant application.
Collaborator Contribution Together with Professor Guillen Fernandez, we have succesfully applied for ERC (European Research Council) grant that has recently been awarded for Euro 3.1 million.
Impact None yet.
Start Year 2010
 
Description University of Warwick 
Organisation University of Warwick
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaborative research with Professor Bruno Frenguelli
Collaborator Contribution Publications
Impact In publications list
Start Year 2007
 
Description Public Discussion Salon, Edinburgh 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact A total of 100 members of the public participated in a a discussion about memory, which resulted in a lengthy discussion session with many questions

Many members of the public repeatedly return to the Encounter discussions
Year(s) Of Engagement Activity 2009
 
Description Public Discussion Salon, Edinburgh 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact A total of 200 members of the public participated in discussions about neuronal circuits (event 1) and mental time travel (event 2), which resulted in a lengthy discussion session with many questions

Many members of the public repeatedly return to the Encounter discussions
Year(s) Of Engagement Activity 2010
 
Description School Activity, Edinburgh 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Schools
Results and Impact 180 pupils attended a workshop 'How we see the brain and what the brain sees' where they learnt about the structure of the brain, how we imaging it and how the brain processes visual information.


Pupils and teachers were very enthusiastic and have asked for similar events.
Year(s) Of Engagement Activity 2008,2009,2010
 
Description School Workshop, Edinburgh 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact A total of 117 pupils from 5 schools participated in the workshop which discussed how the brain stores memories and how this compares to computer memory storage.


Copies of the University student science magazine were distributed as part of the workshop and some pupils subsequently requested neuroscience work placements at the university.
Year(s) Of Engagement Activity 2009,2010