Tatsuya Tsukahara

One of the most fascinating features of the living cells is the ability to modulate their functions based on experience. For example, in the nervous system, neurons that have been highly active attenuate their responses to stimuli, whereas recently inactive neurons boost responses. These forms of adaptation are not only essential for keeping individual cells within a healthy dynamic range but also for appropriate physiological and behavioral responses.

The Tsukahara lab seeks the logic of adaptation, by which neurons use the molecular language – in forms of altered gene and protein expression – to encode experience and optimize neural and circuit functions. By using the mouse olfactory system as a model, our recent study revealed a transcriptional form of adaptation in the peripheral sensory neurons over long timescales like hours to days. This contrasts with well-known forms of adaptation, which is achieved in the brain through the modulation of firing frequency and synaptic weights on relatively short timescales like minutes.

Based on this discovery, we pursue three fundamental questions by using techniques at the intersection of neuroscience and systems biology, such as single-cell and spatial omics, live imaging, optogenetics and chemogenetics, and computational behavioural analyses:

1) What are the molecular mechanisms that couple neural activity, gene expression, and neural functions?

2) How do peripheral sensory neurons respond to signals from inside of the body that signify internal states or life stages (hormones, peptides, and cytokines) and integrate them with the signals from the outside world?

3) How does the transcriptional adaptation in peripheral neurons impact the brain circuits and behaviour in healthy, aged, and disease conditions?