Synapse Biology and Cognition Group

A central research focus of the lab is to elucidate the role of synaptic genes in cognition and disease. To understand how the molecular building blocks at synapses that are critical for establishing and regulating the coordinated wiring and connectivity in the brain, shape complex behaviour, distinct components of cognition and higher order processing in the healthy brain, and in mental disorders where these processes go awry.

Vertebrate synapses have evolved to 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, formation and plasticity of circuits that underlie the regulation of behaviour.

The genetic architecture of mental disorders is complex and heterogenous, but there is mounting evidence for a convergence on disruption of genes that encode postsynaptic proteins, highlighting perturbations at the synapse or ‘synaptopathies’ represents the intersection that cuts across a range of neurodevelopmental and neuropsychiatric disorders. These disorders include anxiety and mood disorders (Depression, Bipolar), Autism Spectrum Disorders and schizophrenia, 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.

Towards bridging the gap between mouse and human cognitive testing, our lab employs innovative behavioural technologies, the touchscreen methodology that Associate Professor Nithianantharajah was involved with early during its development, application and commercialisation at the University of Cambridge. This behavioural tool allows the dissection of higher cognitive functions in rodents that is highly analogous to cognitive assessment of clinical populations, providing avenues to enhance the utility of preclinical animal models for medical translation towards personalised medicine.