Developing better treatments for mental illness: unravelling the molecular machinery at synapses to therapeutically target disruptions in complex behaviour and cognition
Vertebrate synapses contain a large yet intricately organised signalling complex of proteins encompassing neurotransmitter receptors, scaffold proteins and cell adhesion proteins that are critical for synapse specification, function, and plasticity, thus the formation and plasticity of neural circuits that regulate complex behaviour.
Human genetic studies continue to increasingly highlight that disruption of the postsynaptic molecular machinery is a hub for a range of mental health disorders, namely neurodevelopmental and neuropsychiatric disorders. These include anxiety and mood disorders (Depression, Bipolar), schizophrenia and Autism Spectrum Disorders that share overlapping cognitive symptoms. While the importance of postsynaptic proteins in synaptic function and plasticity are strongly appreciated, we know much less about how disrupting the postsynaptic machinery selectively disrupts different components of cognition and higher order processing.
Aims
- Identifying neural circuit changes responsible for adaptive decision making and learning (Project 1).
- Characterising novel drug therapies to target cognitive symptoms in schizophrenia (Project 2).
Our group is focused on understanding the critical role synaptic molecules play in regulating connectivity in the brain that enables complex cognition and higher order processing in the healthy brain, and how these processes go awry in mental disorders.
Project 1 will interrogate decision making and reward-based learning in genetic mouse models to understand how these processes are impaired when excitatory-inhibitory connections in the brain are disrupted. Using novel rodent touchscreen tasks combined with in vivo manipulations (calcium imaging, fibre photometry, optogenetics, chemogenetics), these studies will elucidate disrupted neural processes that underlie impairments in these cognitive behaviours in mental disorders.
Project 2 will investigate the efficacy of novel drug targets to reverse cognitive and underlying neural changes in pharmacological and genetic models of schizophrenia, working in collaboration with Monash Institute of Pharmaceutical Sciences. Using rodent touchscreen tasks to probe selective cognitive constructs combined with pharmacology and in vivo manipulations (fibre photometry), these studies will elucidate the effectiveness of novel therapies to address cognitive dysfunction in mental disorders.
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