Manipulating disrupted neuromodulator signalling to treat maladaptive cognitive behaviour in neurodevelopmental psychiatric disorders

The Synapse Biology & Cognition Laboratory is focused on understanding the critical role synaptic genes and proteins play in shaping excitatory/inhibitory wiring and connectivity in the brain, that enables complex cognition and higher order processing in the healthy brain, and in mental conditions where these processes go awry.

Human genetic studies continue to increasingly highlight that disruption of postsynaptic genes is a hub for a range of mental health disorders, namely neurodevelopmental and neuropsychiatric disorders. These include schizophrenia, anxiety and mood disorders (depression, bipolar) and autism spectrum disorders, that share overlapping symptom domains. While the importance of postsynaptic proteins in  synaptic function and plasticity are strongly appreciated, we know much less about the impact of postsynaptic gene mutations in regulating distinct components of cognition and higher order processing.

Modelling the complex cognitive processes routinely assessed in the clinical setting has been challenging in animal models. Using a unique touchscreen methodology provides an innovative tool for dissecting higher cognitive functions in rodents that is highly analogous to cognitive assessment of clinical populations.

Aims

This group use genetically modified mice as models to study how genes important for regulating synapse function and plasticity selectively modulate cognitive behaviour.

They aim to combine in-depth behavioural analysis with advanced in vivo molecular, cellular and imaging techniques. This project will involve cognitive assessment in the touchscreen system combined with in vivo recording of neuromodulators and manipulations (fibre photometry, optogenetics) to elucidate underlying processes.

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