Insights into cognitive neural circuits and treatment of Alzheimer's symptoms
A key hallmark of Alzheimer’s disease is the loss of neurons in brain regions associated with the control of memory and emotion. Neurons in these areas form complex circuits with other brain regions, sending and receiving chemical messages that orchestrate cognitive activity. In order to increase our understanding of these neural networks, Mr Wykes’ research is focused on characterising the function, biochemistry and anatomical connectivity of neurons located in the brainstem area known as the nucleus incertus. These neurons have been shown to promote memory consolidation and cognitive processes by using the amino acid transmitter, GABA, and the neuropeptide, relaxin-3, to modulate the activity of important forebrain areas including the hippocampus. Mr Wykes' studies will provide further insight into how the relaxin-3/nucleus incertus and related systems function in healthy and Alzheimer’s disease-affected brain, and in doing so identify potential therapeutic targets and approaches that may benefit individuals with Alzheimer’s disease and dementia.
For more than a decade the Peptide Neurobiology Laboratory of the Neuropeptides Division at The Florey has studied a network of inhibitory brain neurons, best characterised by their expression of the evolutionarily conserved, neuromodulatory peptide transmitter, ‘relaxin-3’. Relaxin-3 is abundantly expressed in pontine nucleus incertus (NI) neurons, which send axonal projections to numerous other brain regions where relaxin-3 modulates neural communication via activation of the membrane receptor, ‘RXFP3’. These relaxin-3/NI neural networks are thought to represent an ascending arousal system, modulating interrelated affective and cognitive processes including motivated behaviour, stress responses, and spatial and emotional memory. In addition, recent investigations suggest an association between relaxin-3/NI networks and nerve-growth factor (NGF) systems in the brain, with NGF known to support the survival and function of key neuronal populations affected by Alzheimer’s disease. Mr Wykes' project will use a range of techniques to further characterise relaxin-3/NI and associated systems in the brain, including pharmacological approaches, models of neurodegeneration, and viral vector-mediated neuronal expression of engineered cell surface receptors in pharmaco/opto-genetic applications. The results of these studies will improve our current understanding of these important brain networks, which offer considerable potential as novel therapeutic targets in the treatment of Alzheimer’s disease and dementia.
Mr Wykes is currently enrolled as a PhD candidate at The University of Melbourne. He is conducting his thesis research in the Peptide Neurobiology Laboratory at The Florey Institute of Neuroscience and Mental Health, under the supervision of Associate Professor Andrew Gundlach, Professor Ross Bathgate and Dr Sherie Ma. He began his PhD in July 2016, and is currently conducting molecular studies to identify possible cell-specific gene promoters and undertaking training in histochemical and physiological techniques.