Neural Plasticity Laboratory

L to R: Mari Kondo, Dr Jess Nithianantharajah and Dr Laura Gray are investigating how an enriched environment can cause changes in the brain.
L to R: Mari Kondo, Dr Jess Nithianantharajah and Dr Laura Gray are investigating how an enriched environment can cause changes in the brain.

Laboratory Head

A/Prof Anthony Hannan BSc (Hons) PhD (Syd)

Contact Details

Email:

anthony.hannan@florey.edu.au

Phone:

+61 (0)3 8344 7316

Fax:

+61 (0)3 9348 1707

Number of

Staff:        4
Students: 6

Research Interests

The Neural Plasticity Group is studying gene-environment interactions and mechanisms of experience-dependent plasticity in the healthy and diseased brain. Of particular interest are brain disorders that involve cognitive and psychiatric symptoms, including Huntington's disease, dementia, depression, schizophrenia and other neurodevelopmental disorders. The research utilises transgenic technology together with correlated behavioural, cellular and molecular analysis, so as to link brain and behaviour in normal and dysfunctional states.

Current Projects

Many brain disorders, including schizophrenia, mental retardation and autism, involve abnormal development and function of the cerebral cortex. The cortex contains many billions of neurons, which are interconnected by trillions of synapses, to form networks underlying our most complex brain functions. The different regions of the cortex gradually begin to differentiate in late embryonic development, but it is only after birth, when environmental stimuli induce patterned neural activity via the sensory pathways, that diverse cortical functions begin to emerge. We are interested in the mechanisms whereby the genetic program underlying maturation of the cortex is dynamically regulated by interaction with the environment. We are focusing on inter- and intra-neuronal signalling pathways that may regulate the way in which neurons are sculpted by sensory activity in the postnatal cortex and exploring whether related mechanisms mediate experience-dependent plasticity of the adult cortex.

We are also interested in understanding gene-environment interactions in the mature cortex and disorders that may involve disruption of normal cortical plasticity, such as Huntington’s disease (HD). HD involves cognitive deficits (dementia), psychiatric symptoms (eg. depression) and a movement disorder (eg. chorea). HD is one of an increasing number of fatal brain diseases known to be caused by expanding trinucleotide repeat sequences (dynamic mutations) in the disease genes. Despite the fact that HD is caused by this heritable mutation in a single gene, we previously discovered, in collaboration with colleagues at Oxford University, that environmental stimulation delays disease onset and progression in a transgenic mouse model of HD. We are currently using this experimental paradigm to identify molecular targets for ‘enviromimetics’: novel therapeutics which mimic or enhance the beneficial effects of environmental stimulation (Hannan, 2004, 2005). Further study of gene-environment interactions and experience-dependent neural plasticity may lead to new therapeutic approaches for HD and other brain disorders (reviewed by Nithianantharajah and Hannan, 2006).

Laboratory Techniques

Funding

Additional Information

Selected Recent Publications

Research Articles

McOmish, C.E., Burrows, E., Howard, M., Scarr, E., Kim, D., Shin, H.-S., Dean, B., van den Buuse, M., Hannan, A.J. (2007) Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration. Molecular Psychiatry [31 July 2007, Epub ahead of print].

Pang, T.Y.C, Stam, N.C, Nithianantharajah, J., Howard, M.L., Hannan, A.J. (2006) Enhanced physical exercise has differential effects on behavioural and BDNF expression deficits in Huntington’s disease transgenic mice. Neuroscience 141: 569-584.

Grote, H.E., Bull, N.D., Howard, M.L., van Dellen, A., Blakemore, C., Bartlett, P.F. and Hannan, A.J. (2005) Cognitive disorders and neurogenesis deficits in Huntington’s disease mice are rescued by fluoxetine. European Journal of Neuroscience 22: 2081-2088.

Mazarakis, N.K., Cybulska-Klosowicz, A., Grote, H., Pang, T., Van Dellen, A., Kossut, M., Blakemore, C. and Hannan, A.J. (2005) Deficits in experience-dependent cortical plasticity and sensory discrimination learning in presymptomatic Huntington’s disease mice. Journal of Neuroscience 25: 3059-3066.

Spires, T.L., Christoffers, K., Molnar, Z., Kind, P.C., Upton, A.L., Blakemore, C. and Hannan, A.J. (2005) Activity-dependent regulation of synapse and dendritic spine morphology in developing barrel cortex requires phospholipase C-β1 signaling. Cerebral Cortex 15: 385-393.

Spires, T.L., Grote, H.E., Varshney, N.K., Cordery, P.M., van Dellen, A., Ladwiniec, A., Blakemore, C. and Hannan, A.J. (2004a) Environmental enrichment rescues protein deficits in a mouse model of Huntington’s disease, indicating a possible disease mechanism. Journal of Neuroscience 24: 2270-2276.

Spires, T.L., Grote, H.E., Varshney, N.K., Garry, S., Cordery, P.M., van Dellen, A., Blakemore, C. and Hannan, A.J. (2004b) Dendritic spine pathology and deficits in experience-dependent dendritic plasticity in R6/1 Huntington’s disease transgenic mice. European Journal of Neuroscience 19: 2799-2807.

Hannan, A.J., Blakemore, C., Katsnelson, A., Vitallis, T., Huber, K., Bear, M., Kim, D., Shin, H-S. and Kind, P.C. (2001) PLC-β1, activated via mGluRs, mediates activity-dependent differentiation in the cerebral cortex. Nature Neuroscience 4: 282-288.

Van Dellen, A., Blakemore, C., Deacon, R., York, D. and Hannan, A.J. (2000a) Delaying the onset of Huntington’s in mice. Nature 404: 721-722.

Hannan, A.J., Servotte, S., Katsnelson, A., Sisodiya, S., Blakemore, C., Squier, M. and Molnar, Z. (1999) Characterization of nodular neuronal heterotopia in children. Brain 122: 219-238.

Review Articles

Nithianantharajah, J. and Hannan, A.J. (2007) Dynamic mutations as digital genetic modulators of brain development, function and dysfunction. Bioessays  29: 525-535.

McOmish, C.E. and Hannan, A.J. Enviromimetics: Exploring gene-environment interactions to identify therapeutic targets for brain disorders. Expert Opinion in Therapeutic Targets  11: 899-913.

Spires, T.L. and Hannan, A.J. (2007) Molecular mechanisms mediating pathological plasticity in Huntington’s disease and Alzheimer’s disease. Journal of Neurochemistry 100: 874-882.

Grote, H.E. and Hannan, A.J.  (2007) Regulators of adult neurogenesis in the healthy and diseased brain. Clinical and Experimental Pharmacology and Physiology 34: 533-545.

Nithianantharajah, J. and Hannan, A.J. (2006) Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nature Reviews Neuroscience 7: 697-709.

Spires, T.L. and Hannan, A.J. (2005) Nature, nurture and neurology: Gene-environment interactions in neurodegenerative disease. FEBS Journal 272: 2347-2361.

Van Dellen, A., Grote, H.E. and Hannan, A.J. (2005) Gene-environment interactions, neuronal dysfunction and pathological plasticity in Huntington’s disease. Clinical and Experimental Pharmacology and Physiology 32: 1007-1019.

Hannan, A.J. (2005) Novel therapeutic targets for Huntington’s disease. Expert Opinion on Therapeutic Targets 9: 639-650.

Research