Award details

The neural basis of temporal processing in predictive learning

Reference	BB/M009440/1
Principal Investigator / Supervisor	Professor David Sanderson
Co-Investigators / Co-Supervisors
Institution	Durham University
Department	Psychology
Funding type	Research
Value (£)	395,066
Status	Completed
Type	Research Grant
Start date	01/03/2015
End date	14/03/2018
Duration	36 months

Abstract

Animals form associations between events when they are experienced in close temporal proximity. However, temporal contiguity is not sufficient for learning to occur. In addition there must be a contingency between events. Models of learning state that the processing of the temporal information provided by events is necessary for determining whether there is temporal contingency, but evidence has led to a number of differing accounts of how this is achieved. In recent years our knowledge of how contingency learning is achieved in the brain, through a prediction error learning mechanism, has greatly increased. In contrast, little is know about the neural basis of the temporal processing that allows prediction error learning to occur. However, my recent findings demonstrate that the GluA1 AMPA receptor subunit is important for temporal processing. Importantly, its role in temporal processing is dissociable from the role of hippocampal NMDA receptors suggesting that they contribute to separate mechanisms of temporal processing in the brain. The aim of the grant is to identify the neural basis of temporal processing in predictive learning. This will be achieved by behavioural experiments using genetically modified mice that lack GluA1 or have a selective knockout of the obligatory GluN1 NDMA receptor in the hippocampus. Mice will be tested on learning tasks that dissociate different components of temporal processing in predictive learning. The work will determine the precise contribution of GluA1 and hippocampal NMDA receptors to temporal processing in predictive learning.

Summary

Animals are able to anticipate the occurrence of important events in the environment, such as the availability of food or imminent danger, by learning that particular cues signals those events. Predictive learning is achieved most readily when events occur together in close temporal proximity. Theories of learning state that animals learn temporal contingencies between events by processing of the temporal information provided by those events. However, there are a number of ways in which temporal information can be used in predictive learning. For example, in addition to learning that events happened close together in time (coincidence detection), temporal information can be used to calculate the relative rate at which a particular event occurs, or can be used to form a temporal map of events such that one cue can provide information of when a particular event will occur. Currently, little is know about the neural basis of temporal processing that allows predictive learning to occur. However, my recent research suggests that the GluA1 subunit of the AMPA receptor for the excitatory neurotransmitter, glutamate plays a role in temporal processing. GluA1 is known to be important for the some functions of the hippocampus, a brain region that is vital for learning and memory. However, in contrast to the role of GluA1, the hippocampus, and in particular, hippocampal NMDA receptors appear to play a rather different role in temporal processing. The aim of the grant is to identify the neural basis of temporal processing in predictive learning. This will be achieved by testing different accounts of the function of GluA1 and hippocampal NMDA receptors in predictive learning. Genetically modified mice that lack the particular receptor subunits will be tested in learning tasks that assess different components of temporal processing. The work will provide a crucial advance in understanding of how learning is achieved in the brain. Importantly, by understanding the neural basisof learning this will then help to identify the causes of impaired learning and cognition that occur in aging and in disease states such as psychosis.

Impact Summary

Who will benefit from the research? The work will benefit the academic community interested in understanding the conditions of learning and the neural basis of learning. It will also benefit pharmaceutical companies in developing appropriate therapeutic treatments for impaired cognition in neuropsychiatric and neurodegenerative diseases. This, in turn, may benefit people who suffer from abnormal cognitive and behavioural processes. Finally, the research will benefit the general public by increasing understanding of psychology and neurobiology. How will they benefit from the research? The scientific community will benefit from the knowledge that we gain from the studies, that we will report in high profile journals and national and international conferences. The work will be of great importance for a wide range of disciplines and the knowledge that we will gain will aid the development of new empirical and theoretical work in understanding learning. Particularly, the question of how temporal information is used in learning is of fundamental importance for the field of synaptic plasticity in which there is an assumption that learning is a process of temporal coincidence detection. The proposed work directly tests this issue. The pharmaceutical industry will benefit from the research for two reasons. First, basic science in understanding the psychological and neurobiological basis of learning will aid the development of appropriate therapeutic treatments for disorders that lead to impaired learning. Second, and more specifically, the gene that encodes for GluA1 shows genome wide associations to schizophrenia (Ripke et al., 2013). Therefore, the project has crucial implications for understanding the potential causes and treatments of loss of cognitive ability in psychosis. The development of drug treatments may increase the economic competitiveness of the UK and will benefit sufferers of learning disorders in this country and overseas. What will be done to ensure that they have the opportunity to benefit from the research? The work will initially be reported at scientific meetings that attract researchers and clinicians. The work will then be reported in high profile journals, and will be made available through Durham Research Online, which provides green standard open access. We will also liaise with the Durham University communications team for reporting the results to the media. The other methods are described in the pathways to impact plan, but in brief we will liaise directly with pharmaceutical companies and clinicians to ensure that the potential benefit is maximized.

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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