A novel approach to record, stimulate, and untangle the function of the serotonergic system in the primate brain.

Serotonin is a key neuromodulator in the primate brain. However, its role in cognition and behaviour remains unclear. This is because we lack appropriate methods for causal manipulation of the neuromodulatory systems in primates. This proposal aims to deliver a fundamental new understanding of the serotonin system using an emerging non-invasive technology: blood-brain-barrier opening and targeted drug delivery with transcranial ultrasound. Having established the feasibility and safety of this method for manipulating the serotonin system in non-human primates, I now aim to apply it to understand serotonin’s role in key cognitive functions. I will address the following questions:

1. How does targeted manipulation of the serotonin system in the primate frontal cortex influence behaviour?

2. How does it influence patterns of brain activity?

3. Where in the brain do any observed effects of serotonin on behaviour originate?

4. Does perturbing the serotonin system influence cellular-level representation of behaviour? I will answer these questions by measuring changes in behaviour and brain using behavioural modelling, functional magnetic resonance imaging and spectroscopy (fMRI/MRS), and single-unit recordings. This will provide an integrative account of serotonin function in the primate brain and can have a substantial impact given the role of serotonin in mental health.