Dr Kerrie Thomas
Reader, Operations Director Neuroscience and Mental Health Innovation Institute, Co-Director of the Hodge Centre for Neuropsychiatric Immunology in Cardiff
- ThomasKL5@caerdydd.ac.uk
- +44 29206 88344
- Adeilad Hadyn Ellis, Heol Maendy, Caerdydd, CF24 4HQ
Trosolwyg
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.
Cyhoeddiad
2024
- Wellard, N. L., Clifton, N. E., Rees, E., Thomas, K. L. and Hall, J. 2024. The association of hippocampal long-term potentiation-induced gene expression with genetic risk for psychosis. International Journal of Molecular Sciences 25(2), article number: 946. (10.3390/ijms25020946)
2023
- Griesius, S. et al. 2023. A mild impairment in reversal learning in a bowl-digging substrate deterministic task but not other cognitive tests in the Dlg2+/- rat model of genetic risk for psychiatric disorder. Genes, Brain and Behavior 22(6), article number: e12865. (10.1111/gbb.12865)
- Indrigo, M. et al. 2023. Nuclear ERK1/2 signaling potentiation enhances neuroprotection and cognition via Importinα1/KPNA2. EMBO Molecular Medicine 15(11), article number: e15984. (10.15252/emmm.202215984)
2022
- Moon, A. L., Clifton, N. E., Wellard, N., Thomas, K. L., Hall, J. and Brydges, N. M. 2022. Social interaction following prepubertal stress alters prefrontal gene expression associated with cell signalling and oligodendrocytes. Translational Psychiatry 12(1), article number: 516. (10.1038/s41398-022-02280-7)
- Griesius, S. et al. 2022. Reduced expression of the psychiatric risk gene DLG2 (PSD93) impairs hippocampal synaptic integration and plasticity. Neuropsychopharmacology 47, pp. 1367-1378. (10.1038/s41386-022-01277-6)
- Waldron, S. et al. 2022. Behavioural and molecular characterisation of the Dlg2 haploinsufficiency rat model of genetic risk for psychiatric disorder. Genes, Brain and Behavior 21(4), article number: e12797. (10.1111/gbb.12797)
- Pass, R., Haan, N., Humby, T., Wilkinson, L. S., Hall, J. and Thomas, K. L. 2022. Selective behavioural impairments in mice heterozygous for the cross disorder psychiatric risk gene DLG2. Genes, Brain and Behavior 21(4), article number: e12799. (10.1111/gbb.12799)
- Namkung, H., Thomas, K. L., Hall, J. and Sawa, A. 2022. Parsing neural circuits of fear learning and extinction across basic and clinical neuroscience: Towards better translation. Neuroscience and Biobehavioral Reviews 134, article number: 104502. (10.1016/j.neubiorev.2021.12.025)
2021
- Notter, T. et al. 2021. Neuronal activity increases translocator protein (TSPO) levels. Molecular Psychiatry 26, pp. 2025-2037. (10.1038/s41380-020-0745-1)
- Tigaret, C. M. et al. 2021. Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by hemizygosity of the psychiatric risk gene Cacna1c. Molecular Psychiatry 26, pp. 1748-1760. (10.1038/s41380-020-01001-0)
2020
- Moon, A. L., Brydges, N. M., Wilkinson, L. S., Hall, J. and Thomas, K. L. 2020. Cacna1c hemizygosity results in aberrant fear conditioning to neutral stimuli. Schizophrenia Bulletin 46(5), pp. 1231-1238. (10.1093/schbul/sbz127)
- Clifton, N. E., Thomas, K. L., Wilkinson, L. S., Hall, J. and Trent, S. 2020. FMRP and CYFIP1 at the synapse and their role in psychiatric vulnerability. Complex Psychiatry (10.1159/000506858)
- Brydges, N. M., Best, C. and Thomas, K. 2020. Female HPA axis displays heightened sensitivity to pre-pubertal stress. Stress 23(2), pp. 190-200. (10.1080/10253890.2019.1658738)
2019
- Brydges, N. M. et al. 2019. Childhood stress impairs social function through AVP-dependent mechanisms. Translational Psychiatry 9(1), article number: 330. (10.1038/s41398-019-0678-0)
- Sykes, L. et al. 2019. Genetic variation in the psychiatric risk gene CACNA1C modulates reversal learning across species. Schizophrenia Bulletin 45(5), pp. 1024-1032. (10.1093/schbul/sby146)
- Moon, A., Brydges, N., Thomas, K. and Hall, J. 2019. Su13: Genetic variation in 'calcium voltage-gated channel subunit alpha1c (cacna1c): interactions with prepubertal stress and impact on hippocampal dependent learning. European Neuropsychopharmacology 29(S4), pp. S1274-S1275. (10.1016/j.euroneuro.2018.08.377)
- Clifton, N., Trent, S., Thomas, K. and Hall, J. 2019. Regulation and function of activity-dependent Homer in synaptic plasticity. Molecular Neuropsychiatry 5(3), pp. 147-161. (10.1159/000500267)
- Clifton, N. E. et al. 2019. Dynamic expression of genes associated with schizophrenia and bipolar disorder across development. Translational Psychiatry 9, article number: 74. (10.1038/s41398-019-0405-x)
2018
- Brydges, N. M., Moon, A., Rule, L., Watkin, H., Thomas, K. L. and Hall, J. 2018. Sex specific effects of pre-pubertal stress on hippocampal neurogenesis and behaviour. Translational Psychiatry 8, article number: 271. (10.1038/s41398-018-0322-4)
- Sykes, L., Clifton, N., Hall, J. and Thomas, K. L. 2018. Regulation of the expression of the psychiatric risk gene Cacna1c during associative learning. Molecular Neuropsychiatry 4, pp. 149-157. (10.1159/000493917)
- Moon, A. L., Haan, N., Wilkinson, L. S., Thomas, K. L. and Hall, J. 2018. CACNA1C: Association with pychiatric disorders, behavior, and neurogenesis. Schizophrenia Bulletin 44(5), pp. 958-965. (10.1093/schbul/sby096)
- Clifton, N., Thomas, K. and Hall, J. 2018. The effect of ketamine on the consolidation and extinction of contextual fear memory. Journal of Psychopharmacology 32(2), pp. 156-162. (10.1177/0269881117748903)
2017
- Clifton, N., Cameron, D., Trent, S., Sykes, L. H., Thomas, K. L. and Hall, J. 2017. Hippocampal regulation of postsynaptic density Homer1 by associative learning. Neural Plasticity 2017, article number: 5959182. (10.1155/2017/5959182)
- Clifton, N. E. et al. 2017. Schizophrenia copy number variants and associative learning. Molecular Psychiatry 22(2), pp. 178-182. (10.1038/mp.2016.227)
- Trent, S., Phillip, B., Hall, J. and Thomas, K. 2017. AMPA receptors control fear extinction through an Arc-dependent mechanism. Learning and Memory 24, pp. 375-380. (10.1101/lm.045013.117)
2016
- Frizzati, A., Milczarek, M. M., Sengpiel, F., Thomas, K. L., Dillingham, C. M. and Vann, S. D. 2016. Comparable reduction in Zif268 levels and cytochrome oxidase activity in the retrosplenial cortex following mammillothalamic tract lesions. Neuroscience 330, pp. 39-49. (10.1016/j.neuroscience.2016.05.030)
- Scholz, B., Doidge, A. N., Barnes, P., Hall, J., Wilkinson, L. S. and Thomas, K. L. 2016. The regulation of cytokine networks in hippocampal CA1 differentiates extinction from those required for the maintenance of contextual fear memory after recall. PLoS ONE 11(5), article number: e0153102. (10.1371/journal.pone.0153102)
2015
- Trent, S., Barnes, P., Hall, J. and Thomas, K. L. 2015. Rescue of long-term memory after reconsolidation blockade. Nature Communications 6, article number: 7897. (10.1038/ncomms8897)
- Hall, J., Trent, S., Thomas, K. L., O'Donovan, M. C. and Owen, M. J. 2015. Genetic risk for schizophrenia: convergence on synaptic pathways Involved in plasticity. Biological Psychiatry 77(1), pp. 52-68. (10.1016/j.biopsych.2014.07.011)
2012
- Barnes, P. A., Kirtley, A. and Thomas, K. L. 2012. Quantitatively and qualitatively different cellular processes are engaged in CA1 during the consolidation and reconsolidation of contextual fear memory. Hippocampus 22(2), pp. 149-171. (10.1002/hipo.20879)
2010
- Amin, E., Wright, N. F., Poirier, G. L., Thomas, K. L., Erichsen, J. T. and Aggleton, J. P. 2010. Selective lamina dysregulation in granular retrosplenial cortex (area 29) after anterior thalamic lesions: an in situ hybridization and trans-neuronal tracing study in rats. Neuroscience 169(3), pp. 1255-1267. (10.1016/j.neuroscience.2010.05.055)
- Kirtley, A. and Thomas, K. L. 2010. The exclusive induction of extinction is gated by BDNF. Learning & Memory 17(12), pp. 612-619. (10.1101/lm.1877010)
- Cunha, C., Brambilla, R. and Thomas, K. L. 2010. A simple role for BDNF in learning and memory?. Frontiers in Molecular Neuroscience 3, article number: 1. (10.3389/neuro.02.001.2010)
2008
- Poirier, G. L., Shires, K. L., Sugden, D., Amin, E., Thomas, K. L., Carter, D. A. and Aggleton, J. P. 2008. Anterior thalamic lesions produce chronic and profuse transcriptional deregulation in retrosplenial cortex: A model of retrosplenial hypoactivity and covert pathology. Thalamus and Related Systems 4(1), pp. 59-77.
- Barnes, P. and Thomas, K. L. 2008. Proteolysis of proBDNF is a key regulator in the formation of memory. PLoS ONE 3(9), article number: e3248. (10.1371/journal.pone.0003248)
2006
- Thomas, K. L. 2006. Plot against pot. Nature Medicine 12(3), pp. 281-283. (10.1038/nm0306-281)
2005
- Lee, J. L. C., Di Ciano, P., Thomas, K. L. and Everitt, B. J. 2005. Disrupting reconsolidation of drug memories reduces cocaine-seeking behavior. Neuron, pp. 795-801. (10.1016/j.neuron.2005.08.007)
- Thomas, K. L. and Davies, A. 2005. Neurotrophins: a ticket to ride for BDNF. Current Biology 15(7), pp. R262-R264. (10.1016/j.cub.2005.03.023)
2004
- Lee, J. L., Everitt, B. J. and Thomas, K. L. 2004. Independent cellular processes for hippocampal memory consolidation and reconsolidation. Science Vol 30(5672), pp. 839-843. (10.1126/science.1095760)
2003
- Thomas, K. L., Arroyo, M. and Everitt, B. J. 2003. Induction of the learning and plasticity-associated gene Zif268 following exposure to a discrete cocaine-associated stimulus. European Journal of Neuroscience 17(9), pp. 1964-1972. (10.1046/j.1460-9568.2003.02617.x)
2002
- Thomas, K. L., Hall, J. and Everitt, B. J. 2002. Cellular imaging with zif268 expression in the rat nucleus accumbens and frontal cortex further dissociates the neural pathways activated following the retrieval of contextual and cued fear memory. European Journal of Neuroscience 16(9), pp. 1789-1796. (10.1046/j.1460-9568.2002.02247.x)
2001
- Thomas, K. L. and Everitt, B. 2001. Limbic-cortical-ventral striatal activation during retrieval of a discrete cocaine-associated stimulus: a cellular imaging study with gamma protein kinase C expression. Journal of Neuroscience Vol 21(7), pp. 2526-2535.
- Hall, J., Thomas, K. L. and Everitt, B. J. 2001. Cellular imaging of zif268 Expression in the hippocampus and amygdala during contextual and cued fear memory retrieval: selective activation of hippocampal CA1 neurons during the recall of contextual memories. Journal of Neuroscience Vol 21(6), pp. 2186-2193.
- Hall, J., Thomas, K. L. and Everitt, B. J. 2001. Cellular imaging of zif268 expression in the hippocampus and amygdala during contextual and cued fear memory retrieval: selective activation of hippocampal CA1 neurons during the recall of contextual memories.. Journal of Neuroscience 21(6), pp. 2186-2193.
- Hall, J., Thomas, K. L. and Everitt, B. J. 2001. Fear memory retrieval induces CREB phosphorylation and Fos expression within the amygdala. European Journal of Neuroscience 13(7), pp. 1453-1458. (10.1046/j.0953-816x.2001.01531.x)
Erthyglau
- Wellard, N. L., Clifton, N. E., Rees, E., Thomas, K. L. and Hall, J. 2024. The association of hippocampal long-term potentiation-induced gene expression with genetic risk for psychosis. International Journal of Molecular Sciences 25(2), article number: 946. (10.3390/ijms25020946)
- Griesius, S. et al. 2023. A mild impairment in reversal learning in a bowl-digging substrate deterministic task but not other cognitive tests in the Dlg2+/- rat model of genetic risk for psychiatric disorder. Genes, Brain and Behavior 22(6), article number: e12865. (10.1111/gbb.12865)
- Indrigo, M. et al. 2023. Nuclear ERK1/2 signaling potentiation enhances neuroprotection and cognition via Importinα1/KPNA2. EMBO Molecular Medicine 15(11), article number: e15984. (10.15252/emmm.202215984)
- Moon, A. L., Clifton, N. E., Wellard, N., Thomas, K. L., Hall, J. and Brydges, N. M. 2022. Social interaction following prepubertal stress alters prefrontal gene expression associated with cell signalling and oligodendrocytes. Translational Psychiatry 12(1), article number: 516. (10.1038/s41398-022-02280-7)
- Griesius, S. et al. 2022. Reduced expression of the psychiatric risk gene DLG2 (PSD93) impairs hippocampal synaptic integration and plasticity. Neuropsychopharmacology 47, pp. 1367-1378. (10.1038/s41386-022-01277-6)
- Waldron, S. et al. 2022. Behavioural and molecular characterisation of the Dlg2 haploinsufficiency rat model of genetic risk for psychiatric disorder. Genes, Brain and Behavior 21(4), article number: e12797. (10.1111/gbb.12797)
- Pass, R., Haan, N., Humby, T., Wilkinson, L. S., Hall, J. and Thomas, K. L. 2022. Selective behavioural impairments in mice heterozygous for the cross disorder psychiatric risk gene DLG2. Genes, Brain and Behavior 21(4), article number: e12799. (10.1111/gbb.12799)
- Namkung, H., Thomas, K. L., Hall, J. and Sawa, A. 2022. Parsing neural circuits of fear learning and extinction across basic and clinical neuroscience: Towards better translation. Neuroscience and Biobehavioral Reviews 134, article number: 104502. (10.1016/j.neubiorev.2021.12.025)
- Notter, T. et al. 2021. Neuronal activity increases translocator protein (TSPO) levels. Molecular Psychiatry 26, pp. 2025-2037. (10.1038/s41380-020-0745-1)
- Tigaret, C. M. et al. 2021. Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by hemizygosity of the psychiatric risk gene Cacna1c. Molecular Psychiatry 26, pp. 1748-1760. (10.1038/s41380-020-01001-0)
- Moon, A. L., Brydges, N. M., Wilkinson, L. S., Hall, J. and Thomas, K. L. 2020. Cacna1c hemizygosity results in aberrant fear conditioning to neutral stimuli. Schizophrenia Bulletin 46(5), pp. 1231-1238. (10.1093/schbul/sbz127)
- Clifton, N. E., Thomas, K. L., Wilkinson, L. S., Hall, J. and Trent, S. 2020. FMRP and CYFIP1 at the synapse and their role in psychiatric vulnerability. Complex Psychiatry (10.1159/000506858)
- Brydges, N. M., Best, C. and Thomas, K. 2020. Female HPA axis displays heightened sensitivity to pre-pubertal stress. Stress 23(2), pp. 190-200. (10.1080/10253890.2019.1658738)
- Brydges, N. M. et al. 2019. Childhood stress impairs social function through AVP-dependent mechanisms. Translational Psychiatry 9(1), article number: 330. (10.1038/s41398-019-0678-0)
- Sykes, L. et al. 2019. Genetic variation in the psychiatric risk gene CACNA1C modulates reversal learning across species. Schizophrenia Bulletin 45(5), pp. 1024-1032. (10.1093/schbul/sby146)
- Moon, A., Brydges, N., Thomas, K. and Hall, J. 2019. Su13: Genetic variation in 'calcium voltage-gated channel subunit alpha1c (cacna1c): interactions with prepubertal stress and impact on hippocampal dependent learning. European Neuropsychopharmacology 29(S4), pp. S1274-S1275. (10.1016/j.euroneuro.2018.08.377)
- Clifton, N., Trent, S., Thomas, K. and Hall, J. 2019. Regulation and function of activity-dependent Homer in synaptic plasticity. Molecular Neuropsychiatry 5(3), pp. 147-161. (10.1159/000500267)
- Clifton, N. E. et al. 2019. Dynamic expression of genes associated with schizophrenia and bipolar disorder across development. Translational Psychiatry 9, article number: 74. (10.1038/s41398-019-0405-x)
- Brydges, N. M., Moon, A., Rule, L., Watkin, H., Thomas, K. L. and Hall, J. 2018. Sex specific effects of pre-pubertal stress on hippocampal neurogenesis and behaviour. Translational Psychiatry 8, article number: 271. (10.1038/s41398-018-0322-4)
- Sykes, L., Clifton, N., Hall, J. and Thomas, K. L. 2018. Regulation of the expression of the psychiatric risk gene Cacna1c during associative learning. Molecular Neuropsychiatry 4, pp. 149-157. (10.1159/000493917)
- Moon, A. L., Haan, N., Wilkinson, L. S., Thomas, K. L. and Hall, J. 2018. CACNA1C: Association with pychiatric disorders, behavior, and neurogenesis. Schizophrenia Bulletin 44(5), pp. 958-965. (10.1093/schbul/sby096)
- Clifton, N., Thomas, K. and Hall, J. 2018. The effect of ketamine on the consolidation and extinction of contextual fear memory. Journal of Psychopharmacology 32(2), pp. 156-162. (10.1177/0269881117748903)
- Clifton, N., Cameron, D., Trent, S., Sykes, L. H., Thomas, K. L. and Hall, J. 2017. Hippocampal regulation of postsynaptic density Homer1 by associative learning. Neural Plasticity 2017, article number: 5959182. (10.1155/2017/5959182)
- Clifton, N. E. et al. 2017. Schizophrenia copy number variants and associative learning. Molecular Psychiatry 22(2), pp. 178-182. (10.1038/mp.2016.227)
- Trent, S., Phillip, B., Hall, J. and Thomas, K. 2017. AMPA receptors control fear extinction through an Arc-dependent mechanism. Learning and Memory 24, pp. 375-380. (10.1101/lm.045013.117)
- Frizzati, A., Milczarek, M. M., Sengpiel, F., Thomas, K. L., Dillingham, C. M. and Vann, S. D. 2016. Comparable reduction in Zif268 levels and cytochrome oxidase activity in the retrosplenial cortex following mammillothalamic tract lesions. Neuroscience 330, pp. 39-49. (10.1016/j.neuroscience.2016.05.030)
- Scholz, B., Doidge, A. N., Barnes, P., Hall, J., Wilkinson, L. S. and Thomas, K. L. 2016. The regulation of cytokine networks in hippocampal CA1 differentiates extinction from those required for the maintenance of contextual fear memory after recall. PLoS ONE 11(5), article number: e0153102. (10.1371/journal.pone.0153102)
- Trent, S., Barnes, P., Hall, J. and Thomas, K. L. 2015. Rescue of long-term memory after reconsolidation blockade. Nature Communications 6, article number: 7897. (10.1038/ncomms8897)
- Hall, J., Trent, S., Thomas, K. L., O'Donovan, M. C. and Owen, M. J. 2015. Genetic risk for schizophrenia: convergence on synaptic pathways Involved in plasticity. Biological Psychiatry 77(1), pp. 52-68. (10.1016/j.biopsych.2014.07.011)
- Barnes, P. A., Kirtley, A. and Thomas, K. L. 2012. Quantitatively and qualitatively different cellular processes are engaged in CA1 during the consolidation and reconsolidation of contextual fear memory. Hippocampus 22(2), pp. 149-171. (10.1002/hipo.20879)
- Amin, E., Wright, N. F., Poirier, G. L., Thomas, K. L., Erichsen, J. T. and Aggleton, J. P. 2010. Selective lamina dysregulation in granular retrosplenial cortex (area 29) after anterior thalamic lesions: an in situ hybridization and trans-neuronal tracing study in rats. Neuroscience 169(3), pp. 1255-1267. (10.1016/j.neuroscience.2010.05.055)
- Kirtley, A. and Thomas, K. L. 2010. The exclusive induction of extinction is gated by BDNF. Learning & Memory 17(12), pp. 612-619. (10.1101/lm.1877010)
- Cunha, C., Brambilla, R. and Thomas, K. L. 2010. A simple role for BDNF in learning and memory?. Frontiers in Molecular Neuroscience 3, article number: 1. (10.3389/neuro.02.001.2010)
- Poirier, G. L., Shires, K. L., Sugden, D., Amin, E., Thomas, K. L., Carter, D. A. and Aggleton, J. P. 2008. Anterior thalamic lesions produce chronic and profuse transcriptional deregulation in retrosplenial cortex: A model of retrosplenial hypoactivity and covert pathology. Thalamus and Related Systems 4(1), pp. 59-77.
- Barnes, P. and Thomas, K. L. 2008. Proteolysis of proBDNF is a key regulator in the formation of memory. PLoS ONE 3(9), article number: e3248. (10.1371/journal.pone.0003248)
- Thomas, K. L. 2006. Plot against pot. Nature Medicine 12(3), pp. 281-283. (10.1038/nm0306-281)
- Lee, J. L. C., Di Ciano, P., Thomas, K. L. and Everitt, B. J. 2005. Disrupting reconsolidation of drug memories reduces cocaine-seeking behavior. Neuron, pp. 795-801. (10.1016/j.neuron.2005.08.007)
- Thomas, K. L. and Davies, A. 2005. Neurotrophins: a ticket to ride for BDNF. Current Biology 15(7), pp. R262-R264. (10.1016/j.cub.2005.03.023)
- Lee, J. L., Everitt, B. J. and Thomas, K. L. 2004. Independent cellular processes for hippocampal memory consolidation and reconsolidation. Science Vol 30(5672), pp. 839-843. (10.1126/science.1095760)
- Thomas, K. L., Arroyo, M. and Everitt, B. J. 2003. Induction of the learning and plasticity-associated gene Zif268 following exposure to a discrete cocaine-associated stimulus. European Journal of Neuroscience 17(9), pp. 1964-1972. (10.1046/j.1460-9568.2003.02617.x)
- Thomas, K. L., Hall, J. and Everitt, B. J. 2002. Cellular imaging with zif268 expression in the rat nucleus accumbens and frontal cortex further dissociates the neural pathways activated following the retrieval of contextual and cued fear memory. European Journal of Neuroscience 16(9), pp. 1789-1796. (10.1046/j.1460-9568.2002.02247.x)
- Thomas, K. L. and Everitt, B. 2001. Limbic-cortical-ventral striatal activation during retrieval of a discrete cocaine-associated stimulus: a cellular imaging study with gamma protein kinase C expression. Journal of Neuroscience Vol 21(7), pp. 2526-2535.
- Hall, J., Thomas, K. L. and Everitt, B. J. 2001. Cellular imaging of zif268 Expression in the hippocampus and amygdala during contextual and cued fear memory retrieval: selective activation of hippocampal CA1 neurons during the recall of contextual memories. Journal of Neuroscience Vol 21(6), pp. 2186-2193.
- Hall, J., Thomas, K. L. and Everitt, B. J. 2001. Cellular imaging of zif268 expression in the hippocampus and amygdala during contextual and cued fear memory retrieval: selective activation of hippocampal CA1 neurons during the recall of contextual memories.. Journal of Neuroscience 21(6), pp. 2186-2193.
- Hall, J., Thomas, K. L. and Everitt, B. J. 2001. Fear memory retrieval induces CREB phosphorylation and Fos expression within the amygdala. European Journal of Neuroscience 13(7), pp. 1453-1458. (10.1046/j.0953-816x.2001.01531.x)
Ymchwil
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.
Local Affiliations
- The Hodge Centre of Neuropsychiatric Immunology
- Neuroscience and Mental Health Research Institute (NMHRI)
Collaborators
- 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)