Measuring how excitatory-inhibitory synapse imbalance disrupts neural activity underlying 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 disorders 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. Bridging the gap between preclinical and clinical cognitive testing, the touchscreen methodology that A/Prof Nithianantharajah was involved in early during its development, application and commercialisation at the University of Cambridge, provides an innovative tool for dissecting higher cognitive functions in rodents that is highly analogous to cognitive assessment of clinical populations.
This project aims to measure how excitatory-inhibitory synapse imbalance disrupts neural activity during decision making, flexible learning or mood behaviour in neurodevelopmental psychiatric disorders. It will involve cognitive assessment in the touchscreen system combined with in vivo calcium imaging of neural activity using miniscopes in behaving mice during cognitive behaviour.
This project will use genetically modified mice as models to study how genes important for regulating synapse function and plasticity selectively modulate cognitive behaviour.