Thalamic Sensory Gating in Migraine

1 fully funded 4 year BBSRC CTP PhD studentship between IoPPN & Eli Lilly.

Migraine is the most common neurological disorder globally. There is a major unmet need for mechanistic insight to determine its underlying pathophysiology and novel therapeutic targets. While classically considered a pain condition, migraineurs experience multisensory hypersensitivity to light (photophobia), sound (phonophobia), smell (osmophobia) and touch (allodynia) that indicate a key role for the thalamus.

Understanding the role of the sensory thalamus in modulating migraine susceptibility and chronification is a key challenge. In this project we will build on our prior work highlighting the thalamus as a key relay for visual and sensory migraine-related processing as well as a potential target for anti-migraine therapies.

The broad aim is to determine the role of the thalamus in the abnormal processing of migraine-related multisensory information. It predicts that abnormal thalamic gating of sensory information results in aberrant activation of diverse thalamocortical networks giving rise to the diverse symptomatology of migraine.

The project will map the interactions between multisensory and trigeminal head pain networks in-vivo using state of the art viral tracing techniques (0-12 months). Using a combination of optogenetic/chemogenetic approaches with preclinical behavioural and electrophysiological (thalamic multi-channel electrode recording) models of 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 student will ideally have some experience of in in-vivo skills including surgical, optogenetic/chemogenetic, electrophysiology or behavioural approaches, however, training will be included allowing the student to master a number of highly desirable specialist skills above and beyond standard laboratory procedures.

The student will acquire cutting-edge in-vivo electrophysiological and behavioural techniques to include state of the art opto- and chemogenetic approaches. The project will join one of the world’s leading headache/migraine research laboratories in the department of basic and clinical neuroscience at the IoPPN, KCL with a key industrial partner in Eli Lilly. The student will be expected to conduct a short period of research with Eli Lilly.

The studentship will be part of the wider GERAS Collaborative Training Partnership, a BBSRC-funded Collaborative Training Partnership (CTP) established between Eli Lilly and Company Ltd, Exeter University and King’s College London. Between 2017 and 2023, the CTP will deliver 11 four-year studentships in priority areas of Bioscience for health, World class underpinning bioscience, and Exploiting new ways of working. The research area of GERAS is focused on the biological basis of lifespan and healthy ageing, particularly ageing and the brain. The primary objective is the data-driven generation of new knowledge on the development and maintenance of health across the life course with the long-term objective of promoting health in later life. The training focus of the CTP is on the skills needed to understand complex biological systems from a data perspective, with core training in Bioinformatics, Programming and Coding, Statistics, and Data Science alongside professional skills training. The CTP will provide PhD students with a first-rate, challenging research training experience within the context of mutually beneficial research collaborations.