Dr Kerrie Thomas
Director of Postgraduate Education, Reader
Using contemporary techniques ranging from the genome-wide analysis of gene expression to the post-transcriptional gene silencing, my lab probes the molecular substrates of long-term memory. Focusing on hippocampal-dependent fear memory, we are particularly interested in understanding the cellular and neural processes supporting the formation of new memories and those supporting the maintenance of the memories after recall.
The post-retrieval processes are not a simple recapitulation of those engaged during the consolidation of the original memory. This research will contribute to knowledge of how the brain encodes behaviorally relevant information and how it is refined by experience. This knowledge is of vital importance for understanding the basis of disorders of memory and psychiatric conditions in humans.
Fresh memories need time to stabilise. The process of memory consolidation involves changes protein synthesis in a number of brain regions. These proteins contribute to the enduring synaptic and/or structural modifications that underlie the persistence of the memory trace in the face of an ever-changing brain. However, fully consolidated memories are far from being stable and resistant to disruption. When retrieved and reactivated, memories can be disrupted for a limited time and require reconsolidation to be maintained long term. With repeated recall stable memories can also undergo extinction leading to a decline a learned behavioural response. Like consolidation, reconsolidation and extinction are protein synthesis-dependent memory processes. The brain regions supporting the memory trace can also undergo reorganisation with time.
Using the inhibition of specific signalling proteins in the hippocampus, a structure important for memory in humans and animals, we were the first group to show that the molecular processes underlying long-term fear memory consolidation and reconsolidation are different. This leads us to consider for the first time that the emerging data showing dissociations between molecular events underlying the formation of new memories and the reconsolidation or extinction after recall may be controlled by a single regulatory mechanism. We showed that the neuroimmune system contributes to this regulatory system indicating a new physiological role for the neuroimmune system in memory, as an opposed to pathological roles normally attributed to the immune system in the brain.
Deficits in associative learning are known to be a central feature of psychiatric disorders. Understanding the molecular processes that support the formation of long-term memories and their maintenance after recall is a first key step in providing therapeutic targets for aberrant memory that can produce pathological behaviour in human psychiatric conditions. We have recently discovered that mutations in schizophrenia cases are enriched for genes expressed during fear extinction in the hippocampus, but not genes expressed following consolidation or retrieval. This suggests that the mutations act to impair inhibitory learning in schizophrenia, potentially contributing to the development of core symptoms of the disorder
Currently our work aims to:
- Identify the genes regulated during memory processing using of large throughput profiling and bioinformatics functional analysis.
- Determine the processes and signalling pathways that initiate the differential transcriptional programmes of the component memory processes.
- Investigate the role for several schizophrenia risk genes in normal memory formation using a combination of correlational analysis, targeted interference of protein expression with antisense and lentiviral technologies and novel rat transgenic models of schizophrenia to show a causal link between genes and behaviour.
- The Hodge Centre of Neuropsychiatric Immunology
- Neuroscience and Mental Health Research Institute (NMHRI)
- Prof John Aggleton, School of Psychology, Cardiff University
- Prof Jeremy Hall (Director of NMHRI)
- Prof Lawrence Wilkinson (School of Medicine & School of Psychology)
- Dr Seralynne Vann (School of Psychology)
- Prof Mike Owen (Director of MRC Centre for Neuropsychiatric Genetics and Genomics)
- Prof Mick O’Donovan ( Deputy Director/Clinical Professor, Division of Psychological Medicine and Clinical Neurosciences)
Members of the Thomas Hall Lab
- Caroline Best (Lab manager)
- Rachel Pass (PhD student)
- Anna Moon (PhD student)
- Dr Tzuching Lin (Postdoctoral associate)
- Dr Nicholas Clifton (Postdoctoral fellow)
- Dr Simon Trent (Postdoctoral fellow)