Rare cortical projection-neuron function in arousal, sleep and neuropathology

Research Opportunity
PhD students, Honours students, Master of Biomedical Science
Number of Honour Places Available
1
Number of Master Places Available
1
Primary Supervisor Email Number Webpage
Prof Andrew Gundlach andrew.gundlach@florey.edu.au Personal web page
Co-supervisor Email Number Webpage
Dr Laura Jacobson
Dr Mohsen Nategh

Summary My laboratory seeks to increase our understanding of the neurobiology of neuropeptide/G-protein-coupled receptor (GPCR) systems in health and disease, with the goal of identifying the physiological role of key neural networks in the brain, and developing novel therapeutics for neuropsychiatric disorders. A primary focus of current projects involving several international collaborations is the relaxin-3/RXFP3 system, and the inhibitory (GABA) projection- and inter-neurons that express the peptide and its receptor. New initiatives are targeting the unexplored relaxin/RXFP1 system in brain and its possible roles in neurovascular coupling and sensory/cognitive processing; and the role of the signalling enzyme, CaMKK2 in regulation of brain and behaviour. Projects on these topics will provide training in techniques such as neurochemical phenotyping of target neurons, cell signalling, neuropharmacology, physiology and behaviour.

Project Details

Experimental and in silico data suggest brain relaxin/RXFP1 signalling regulates neural networks that contribute to arousal, attention, memory, and sensory processing; and key characteristics of cortical 'relaxin' neurons and their RXFP1-positive target cells have been revealed. In mouse cortex, relaxin (not Rxfp1) mRNA is expressed by long-projecting (somatostatin/GABA) neurons, which we hypothesise are capable of morphological, neurochemical and synaptic plasticity in response to specific neural inputs and to acute and chronic brain injury. In contrast, Rxfp1 mRNA is expressed by topographically-distributed inhibitory and excitatory neurons in outer and deep cortical layers which are likely targeted by adjacent or distant relaxin neurons, but their nature and function are otherwise uncharacterised.
Thus, this project will investigate populations of cortical neurons that synthesize the peptide, relaxin, and their target neurons that express the neural membrane receptor, RXFP1. We propose relaxin/RXFP1 signalling in areas containing sensory, emotional and cognitive circuits regulates processes, including nerve growth and modification of synapses and the surrounding environment, with links to sleep/wake states, and responses to brain injury. We will assess the gene/protein expression profile of relaxin- and RXFP1-positive neurons in mouse brain (image), and the impact of perturbations such as sleep deprivation and brain pathology on this profile. In collaborative studies, we will also explore how relaxin alters the electrical activity of RXFP1-positive cortical neurons in mice. These studies should reveal the therapeutic potential of a specific brain receptor system for alleviating cognitive and emotional symptoms in neurological disorders.

Research Opportunities

PhD students, Honours students, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

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