Synapse Biology and Cognition Group

Our work aims to uncover the neural basis of complex behavior and cognition, with a specific focus on the critical role the molecular machinery at synapses play in regulating brain connectivity required for complex cognition and higher order processing. We investigate these processes in healthy brains and in mouse models for mental disorders where these processes go awry.

Research interests

  • Synapses
  • Cognition
  • Schizophrenia
  • Depression
  • Autism spectrum disorders

  • Rodent cognitive touchscreen testing
  • Fibre photometry
  • Miniscope cellular imaging
  • Optogenetics
  • Deep-learning

About our research

Bridging the gap between preclinical and clinical cognitive testing, we take a translation focused approach using touchscreen-based tests, an innovative tool for dissecting distinct cognitive domains in rodents that is highly analogous to cognitive assessment of clinical populations.

We combine detailed behavioural analysis with advanced in vivo imaging techniques to measure real time neural activity changes during behaviour. Additionally, we explore treatment strategies to restore cognitive and neural deficits.

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.

Research team

Research team head

Team members

PhD students

  • Marek Ellengerger
  • Ulysse Thivisol

Selected publications

  • 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, 317:114850, doi: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, 11(1):556, doi: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):4740, doi:10.3390/ijms22094740

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