Our Work

Critical Period Plasticity:

Neuronal circuits that process sensory information are shaped by patterns of cellular activity during early brain development called critical periods. The term ‘critical period’ (CP) refers to a specific developmental window during which target systems are sensitive to a specific environmental input. CPs are known to be present in several sensory systems in the brain, such as the barrel representation of whiskers in somatosensory cortex, tonotopic map refinement in auditory cortex and human language acquisition in the Bora’s area and the role of light on the development of the visual system. In this lab, we study on the CP in visual and barrel cortices.

The extraordinary changes during the CP of visual and barrel cortical circuits is maximal but this plasticity is lost by adulthood. This may reflect sequential locks placed on a molecular pathway as the visual and barrel cortices consolidates into a structurally elaborated circuitry. 

Over the years, we have linked the critical period plasticity in neurodevelopment using the mouse visual and barrel cortices. CP can be linked to a specific molecular logic of gene regulation fine-tuned by epigenetics. Epigenetics is a control system of molecular switches, consisting of histone modifications, microRNA, non-coding RNA and DNA methylation, that help fine-tune to the degree in which a gene is activated or repressed. The interaction between environment and epigenetics results in the formation of CP plasticity and impact one's phenotype later on in life.

Properly sequenced critical periods of circuit refinement build up complex cognitive functions, such as language, from more primary modalities. Even slight variation along any of these parameters may collectively inject individual differences in plasticity. These may be further magnified in the higher cognitive capacities of humans built upon a series of sequential CPs. If too narrow a time window is taken, long-lasting changes to system responsiveness may be missed. However, lengthening the considered time window at the expense of sampling rate means subtleties in temporal dynamics of the response are lost. 

Working with clinicians in Institute of Mental Health, we study on epigenetic and transcriptome biomarkers to determine severity of psychosis in schizophrenia and depression.

To expand on epigenetics and the loss of plasticity in neurodegeneration, we are part of the MOE Tier 3 project, "Defining the circuitry underlying dementia" led by Prof. George Augustine in a collaborative project between three leading institutes within Singapore, NTU, NUS and NNI. In this project, we cover three dementia models: Alzheimer's disease, Huntington's disease and Bilateral carotid artery stenosis (BCAS).