Rejuve​​nation of the Aged Brain: Optical Inte​​rrogation of Cortical Dynamics

Improvements in our life expectancy have led to a substantial increase in the proportion of elderly population in developed societies.

In Singapore, approximately one fourth of the population will be 65 or older by 2030. The observation that almost all aged brains exhibit some characteristics related to neurodegeneration makes it critical to understand their mechanisms to prevent and reverse cognitive impairment. Recent animal studies have demonstrated that exchange of blood between young and old animals can reverse ageing-related dysfunctions in several organs. In particular, administration of blood plasma from young animals was shown to be sufficient to rejuvenate aged brains and improve learning and memory. Despite these remarkable results, it remains to be explored how these effects are mediated by activity of neural ensembles. Here we propose to uncover basic operation principles underlying the rejuvenation of cognitive abilities of aged mice by imaging activity of tens of thousands of neurons from multiple brain areas while the mouse is performing a cognitive task. Toward this aim, we set three major objectives.

Objective 1: To establish a behavioural paradigm to quantitatively measure learning impairment in aged mice and whether it is improved through plasma administration (brain rejuvenation).

Objective 2. To probe and compare neural population activity of the young and aged brain and understand how brain rejuvenation mitigates ageing-related abnormality in population dynamics.

Objective 3. To study differences in inhibitory circuits between the young and aged brain and investigate how brain rejuvenation affects their operation modes. By combining an emerging field of brain rejuvenation and state-of-the-art optical technologies in systems neuroscience, the proposed study will pave a unique and novel research avenue in neurobiology of ageing.