Professor Cliff Abraham, Our People, Brain Health Research Centre, University of Otago, New Zealand

Professor Cliff Abraham has played a leading role in promoting neuroscience research and teaching at the university. In 1997, he was elected Fellow of the Royal Society of New Zealand, and in 2007 he was awarded a Royal Society of New Zealand James Cook Fellowship. He chaired the Australasian Winter Conference on Brain Research, New Zealand’s annual neuroscience meeting for 12 years. He is the Otago-based Co-Director of Brain Research New Zealand, a national centre for research excellence.

Professor Abraham is interested in the neural mechanisms of memory and the rules and mechanisms governing synaptic plasticity and memory formation in the brain. His particular focus is on the cellular and molecular events in the hippocampus, a brain structure important for certain kinds of learning and memory. His lab has expertise in electrophysiological, behavioural and immunofluorescent microscopy approaches to studying the mechanisms mediating the induction and persistence of synaptic plasticity in vivo and in vitro, and their relevance to memory.

One of the most likely neural mechanisms mediating memory storage is long-lasting plasticity in the strength of synaptic transmission between neurons. This plasticity includes long-term potentiation (LTP) and long-term depression (LTD) of synaptic efficacy. In collaboration with Professor Warren Tate and Dr Joanna Williams, he is studying the cellular and molecular mechanisms of LTP and LTD in the hippocampus. His investigations of the molecular mechanisms of synaptic plasticity have focused on the roles that gene expression and changes in synaptic proteins, such as glutamate receptors, play in the maintenance of LTP and LTD across time. A further major focus is the mechanisms by which prior neural activity controls the subsequent induction of synaptic plasticity, a set of phenomena he has termed “metaplasticity”.

Professor Abraham also has growing interest in the mechanisms of plasticity disruption in neurological disorders characterized by memory deficits, such as Alzheimer’s disease and schizophrenia. The work on Alzheimer’s focuses on neuroprotective molecules such as secreted amyloid precursor protein-alpha and agmatine. In a related project, he is involved in research aimed at identifying blood biomarkers of Alzheimer’s to help with early diagnosis of the disease

His work is highly collaborative, with partners based locally, nationally and internationally, and he is funded by the New Zealand Health Research and Marsden Councils.

Find out more about Professor Abraham’s research.

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Publications

Abraham, W. C. (2008). Metaplasticity: Tuning synapses and networks for plasticity. Nature Reviews Neuroscience, 9(5), 387-399.

Ryan, M., Tan, V. T. Y., Thompson, N., Guévremont, D., Mockett, B. G., Tate, W. P., Abraham, W. C., Hughes, S. M., & Williams, J. (2021). Lentivirus-mediated expression of human secreted amyloid precursor protein-alpha promotes long-term induction of neuroprotective genes and pathways in a mouse model of Alzheimer’s disease. Journal of Alzheimer's Disease, 79, 1075-1090. doi: 10.3233/JAD-200757

Hegemann, R. U., & Abraham, W. C. (2021). Postsynaptic cell firing triggers bidirectional metaplasticity depending on the LTP induction protocol. Journal of Neurophysiology, 125, 1624-1635. doi: 10.1152/jn.00514.2020

Livingstone, R. W., Elder, M. K., Singh, A., Westlake, C. M., Tate, W. P., Abraham, W. C., & Williams, J. M. (2021). Secreted amyloid precursor protein-alpha enhances LTP through the synthesis and trafficking of Ca²⁺-permeable AMPA receptors. Frontiers in Molecular Neuroscience, 14, 660208. doi: 10.3389/fnmol.2021.660208

Vemula, P. K., Jing, Y., Cicolini, J., Zhang, H., Mockett, B. G., Abraham, W. C., & Liu, P. (2020). Altered brain arginine metabolism with age in the APP_swe/PSEN1_dE9 mouse model of Alzheimer's disease. Neurochemistry International, 140, 104798. doi: 10.1016/j.neuint.2020.104798

Abraham, W. C. (2008). Metaplasticity: Tuning synapses and networks for plasticity. Nature Reviews Neuroscience, 9(5), 387-399.

Journal - Research Article

Reuben, A., Elliott, M. L., Abraham, W. C., Broadbent, J., Houts, R. M., Ireland, D., Knodt, A. R., Poulton, R., Ramrakha, S., … Caspi, A., & Moffitt, T. E. (2020). Association of childhood lead exposure with MRI measurements of structural brain integrity in midlife. JAMA, 324(19), 1970-1979. doi: 10.1001/jama.2020.19998

Journal - Research Article

Kyrke-Smith, M., Logan, B., Abraham, W. C., & Williams, J. M. (2021). Bilateral histone deacetylase 1 and 2 activity and enrichment at unique genes following induction of long-term potentiation in vivo. Hippocampus, 31, 389-407. doi: 10.1002/hipo.23297

Journal - Research Article

Mathiesen, S. N., Lock, J. L., Schoderboeck, L., Abraham, W. C., & Hughes, S. M. (2020). CNS transduction benefits of AAV-PHP.eB over AAV9 are dependent on administration route and mouse strain. Molecular Therapy: Methods & Clinical Development, 19, 447-458. doi: 10.1016/j.omtm.2020.10.011

Journal - Research Article

Chiamulera, C., Piva, A., & Abraham, W. C. (2020). Glutamate receptors and metaplasticity in addiction. Current Opinion in Pharmacology, 56, 39-45. doi: 10.1016/j.coph.2020.09.005

Journal - Research Article

Sateesh, S., & Abraham, W. C. (2021). Neurophysiological and molecular approaches to understanding the mechanisms of learning and memory. Journal of the Royal Society of New Zealand, 51(1), 4-23. doi: 10.1080/03036758.2020.1796719

Journal - Research Other

Morrissey, J. A., Mockett, B. G., Singh, A., Kweon, D., Ohline, S. M., Tate, W. P., Hughes, S. M., & Abraham, W. C. (2019). A C-terminal peptide from secreted amyloid precursor protein-α enhances long-term potentiation in rats and a transgenic mouse model of Alzheimer's disease. Neuropharmacology, 157, 107670. doi: 10.1016/j.neuropharm.2019.107670

Journal - Research Article

Hegemann, R. U., & Abraham, W. C. (2019). Electrophysiological investigation of metabotropic glutamate receptor-dependent metaplasticity in the hippocampus. In C. Burger & M. J. Velardo (Eds.), Glutamate receptors: Methods and protocols: Methods in molecular biology (Vol. 1941). (pp. 79-91). New York, NY: Humana Press. doi: 10.1007/978-1-4939-9077-1_7

Chapter in Book - Research

Ohline, S. M., & Abraham, W. C. (2019). Environmental enrichment effects on synaptic and cellular physiology of hippocampal neurons [Invited]. Neuropharmacology, 145(A), 3-12. doi: 10.1016/j.neuropharm.2018.04.007

Journal - Research Other

Schoderboeck, L., Wicky, H. E., Abraham, W. C., & Hughes, S. M. (2019). Genetic targeting and chemogenetic inhibition of newborn neurons. Human Gene Therapy Methods, 29(6), 259-268. doi: 10.1089/hgtb.2018.182

Journal - Research Article

Mockett, B. G., Guévremont, D., Elder, M. K., Parfitt, K. D., Peppercorn, K., Morrissey, J., Singh, A., Hintz, T. J., … Tate, W. P., Williams, J. M., & Abraham, W. C. (2019). Glutamate receptor trafficking and protein synthesis mediate the facilitation of LTP by secreted amyloid precursor protein-alpha. Journal of Neuroscience, 39(17), 3188-3203. doi: 10.1523/jneurosci.1826-18.2019

Journal - Research Article

Abraham, W. C., Jones, O. D., & Glanzman, D. L. (2019). Is plasticity of synapses the mechanism of long-term memory storage? npj Science of Learning, 4, 9. doi: 10.1038/s41539-019-0048-y

Journal - Research Other

Livingstone, R. W., Elder, M. K., Barrett, M. C., Westlake, C. M., Peppercorn, K., Tate, W. P., Abraham, W. C., & Williams, J. M. (2019). Secreted amyloid precursor protein-alpha promotes arc protein synthesis in hippocampal neurons. Frontiers in Molecular Neuroscience, 12, 198. doi: 10.3389/fnmol.2019.00198

Journal - Research Article

Morrissey, J. A., Bigus, E., Necarsulmer, J. C., Srinivasan, V., Peppercorn, K., O'Leary, D. J., Mockett, B. G., Tate, W. P., Hughes, S. M., … Abraham, W. C. (2019). The tripeptide RER mimics secreted amyloid precursor protein-alpha in upregulating LTP. Frontiers in Cellular Neuroscience, 13, 459. doi: 10.3389/fncel.2019.00459

Journal - Research Article

Singh, A., Jones, O. D., Mockett, B. G., Ohline, S. M., & Abraham, W. C. (2019). Tumor necrosis factor-α-mediated metaplastic inhibition of LTP is constitutively engaged in an Alzheimer's disease model. Journal of Neuroscience, 39(46), 9083-9097. doi: 10.1523/jneurosci.1492-19.2019

Journal - Research Article

Ohline, S. M., Wake, K. L., Hawkridge, M.-V., Dinnunhan, M. F., Hegemann, R. U., Wilson, A., Schoderboeck, L., Logan, B. J., … Hughes, S. M., & Abraham, W. C. (2018). Adult-born dentate granule cell excitability depends on the interaction of neuron age, ontogenetic age and experience. Brain Structure & Function, 223(7), 3213-3228. doi: 10.1007/s00429-018-1685-2

Journal - Research Article

Ryan, M. M., Guévremont, D., Mockett, B. G., Abraham, W. C., & Williams, J. M. (2018). Circulating plasma microRNAs are altered with amyloidosis in a mouse model of Alzheimer's disease. Journal of Alzheimer's Disease, 66(2), 835-852. doi: 10.3233/jad-180385

Journal - Research Article

Tan, V. T. Y., Mockett, B. G., Ohline, S. M., Parfitt, K. D., Wicky, H. E., Peppercorn, K., Schoderboeck, L., Yahaya, M. F. b., Tate, W. P., Hughes, S. M., & Abraham, W. C. (2018). Lentivirus-mediated expression of human secreted amyloid precursor protein-alpha prevents development of memory and plasticity deficits in a mouse model of Alzheimer's disease. Molecular Brain, 11, 7. doi: 10.1186/s13041-018-0348-9

Journal - Research Article

Singh, A., & Abraham, W. C. (2017). Astrocytes and synaptic plasticity in health and disease. Experimental Brain Research, 235(6), 1645-1655. doi: 10.1007/s00221-017-4928-1

Journal - Research Article

Bilkey, D. K., Cheyne, K. R., Eckert, M. J., Lu, X., Chowdhury, S., Worley, P. F., … Abraham, W. C. (2017). Exposure to complex environments results in more sparse representations of space in the hippocampus. Hippocampus, 27(11), 1178-1191. doi: 10.1002/hipo.22762

Journal - Research Article

Mockett, B. G., Richter, M., Abraham, W. C., & Müller, U. C. (2017). Therapeutic potential of secreted amyloid precursor protein APPsα. Frontiers in Molecular Neuroscience, 10, 30. doi: 10.3389/fnmol.2017.00030

Journal - Research Article

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