Stress and flexibility in serotonin signalling

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This NSERC research program will investigate the cellular mechanisms and behavioural consequences of stress-elicited plasticity in brain serotonergic signalling. We will probe the mechanisms that control the excitability of serotonin neurons in the raphe nuclei and those by which they exert their influence in the cerebral cortex. We will also examine how cortical serotonin release affects the performance of complex cognitive tasks. Serotonin plays key roles in cognitive and emotional responses, so we aim to understand its cell and circuit mechanisms and their sensitivity to the effects of stress at different developmental time points.Key foci of this grant are the flexibility of serotonin signalling, how this flexibility is altered by developmental stress, and implications for cognitive behaviour. Broadly, my laboratory investigates the cellular mechanisms of neuromodulation using rodent models, electrophysiological tools, optogenetics, multiphoton imaging, and behavioural and molecular assays. For this grant, we will start with the serotonergic neurons themselves and interrogate the signalling pathways that provide flexibility to respond with different firing patterns on behaviourally-relevant time frames. This work segues naturally into ongoing NSERC research in our lab examining whether mice exposed to prolonged social isolation show changes in serotonin receptor electrophysiological signalling in cerebral cortex and identifying the underlying receptors and channel effectors involved. Finally, we will investigate using in vivo optogenetics the role of cortical serotonin in disrupting performance on a complex attention task under acutely stressful or emotional conditions.This program of NSERC research will train students and postdocs in cutting-edge neuroscience techniques and will advance our understanding of the cellular mechanisms that regulate the serotonin system. The integrated experiments bring together mechanistic studies in the raphe and cortex to understand more fully the flexibility inherent in the serotonergic signalling and the lasting consequences of developmental perturbations. Our behavioural work aims to elucidate the relationship between the cellular and circuit effects of serotonin and its consequences for cognition. Overall, this NSERC program will probe the extent to which our personal history shapes the ability of serotonin to modulate our neural circuitry and behaviour.