Project 32.2: The neural mechanisms of sleep and migraine

Migraine is the 2nd most disabling disorder with over one billion sufferers globally. Attacks are

characterized by repeated bouts of intense pain that are associated with sleep-wake cycles. Changes in

sleep patterns can trigger attacks and sleep disorders are associated with increased migraine frequency.

Conversely, sleep itself is one of the most commonly reported strategies to relieve migraine attacks.

Migraineurs demonstrate hypersensitivity to light (photophobia) and light is a key regulator of sleep,

suggesting a potential shared mechanism. Herein, we will determine why sleep stops migraine and how

sleep disruption can lead to increased attack susceptibility. Our hypothesis is that dysregulation of light-

mediated hypothalamic arousal networks leads to an increased migraine susceptibility. It additionally

proposes that during an attack sleep acts to reset these dysfunctional networks, normalizing the attack.

The project will map the interactions between arousal and head pain networks in-vivo using mouse

genetics and viral tracing (0-12 months). Using a combination of optogenetic/chemogenetic approaches

with preclinical behavioural and electrophysiological models of sleep disruption and migraine, the project

will characterise the functional consequences of their modulation (10-24 months). Finally, we will explore

novel therapeutic targets to modulate these dysfunctional networks (24-36 months) and where

appropriate these will be translated into the clinic.

The study consists of detailed in-vivo approaches and would benefit from a 0+3.5 PhD; however, a 1+3

option is available. The student will develop in-vivo skills including surgical, optogenetic/chemogenetic,

electrophysiology and behavioural approaches, mastering a number of highly desirable specialist skills

above and beyond standard laboratory procedures.