Synapse Biology and Cognition Group
In our group, we are connecting the dots in wiring the brain. We explore how the molecular building blocks at synapses shape complex behaviour and cognition.
About our research
In a changing environment, a challenge for the brain is to adaptively guide behaviour towards survival which involves the processing of sensory information, selecting between actions that will result in a beneficial outcome, and executing these actions. These complex cognitive abilities emerge from the physical architecture of the brain: from circuits to neurons, and the molecular components that comprise the protein signalling complex at synapses. This hardware forms the basis to enable signalling and plasticity within and between brain regions, thus supporting the emergence of behaviour.
- Complex behaviour
- Psychiatric disorders
- Touchscreen tasks
- Fibre photometry
- Calcium imaging
Exploring the role of synaptic genes and plasticity in cognition and disease
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 role of postsynaptic gene mutation in mental conditions
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.
Using touchscreens to bridge the gap between mouse and human testing
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.
- Characterising novel drug therapies to target cognitive symptoms in schizophrenia
- Deep-learning based tracking of behaviour in preclinical models for mental illness
- Developing better treatments for mental illness: unravelling the molecular machinery at synapses to therapeutically target disruptions in complex behaviour and cognition
- Elucidating the molecular drivers underlying schizophrenia
- Manipulating disrupted neuromodulator signalling to treat maladaptive cognitive behaviour in neurodevelopmental psychiatric disorders
- Marek Ellengerger
- Ulysse Thivisol
- Mia Dore
- Juulke Castelijn
- Snelleksz, M., Rossell, S.L., Gibbons, A., Nithianantharajah, J. and Dean, B. (2022). Evidence that the frontal pole has a significant role in the pathophysiology of schizophrenia. Psychiatry Research, p.114850. doi:https://doi.org/10.1016/j.psychres.2022.114850.
- Choy, K.H.C., Luo, J.K., Wannan, C.M.J., Laskaris, L., Merritt, A., Syeda, W.T., Sexton, P.M., Christopoulos, A., Pantelis, C. and Nithianantharajah, J. (2021). Cognitive behavioral markers of neurodevelopmental trajectories in rodents. Translational Psychiatry, [online] 11(1), p.556. doi:https://doi.org/10.1038/s41398-021-01662-7.
- Kagan, B.J., Ermine, C.M., Frausin, S., Parish, C.L., Nithianantharajah, J. and Thompson, L.H. (2021). Focal Ischemic Injury to the Early Neonatal Rat Brain Models Cognitive and Motor Deficits with Associated Histopathological Outcomes Relevant to Human Neonatal Brain Injury. International Journal of Molecular Sciences, 22(9), p.4740. doi:https://doi.org/10.3390/ijms22094740