Chemogenetic silencing of nociceptor populations (360G-Wellcome-109116_Z_15_A)
Nociceptors are heterogeneous sensory neurons and due to single cell sequencing, our understanding of their diversity is expanding. To understand which nociceptor populations are responsible for different pain-related behavioural phenotypes, we aim to employ a chemogenetic silencing tool to allow reversible inhibition of selected cells in vivo. Our chemogenetic tool of choice is the mutated glutamate-gated chloride channel (GluCl). Initially, we expressed the channel in cultured DRG neurons and using patch-clamp recordings observed dose dependent silencing upon application of the agonist ivermectin (IVM). We have optimised the channel and assessed channel functionality in vitro and in vivo following AAV-mediated delivery. Behavioural assays suggest IVM treated animals had significantly elevated pain thresholds compared to vehicle treated mice. Using rodent pain models (SNI, CCI) in conjunction with conditioned place preference tasks, we aim to further establish this method of nociceptor silencing as a potential therapeutic. Furthermore, to understand nociceptor heterogeneity our first target population will be the A-delta nociceptors. Using transgenic strategies we hope to selectively express GluCl in A-delta nociceptors and perform electrophysiological and sensitive behavioural assays pre and post IVM treatment. Ultimately this project aims to facilitate the discovery of novel nociceptor populations, their roles and their therapeutic potential.
Where is this data from?
This data was originally published by The Wellcome Trust. If you see something about your organisation or the funding it has received on this page that doesn't look right you can submit a grantee amendment request. You can hover over codes from standard codelists to see the user-friendly name provided by 360Giving.
Grant Details
Amount Awarded | 31040 |
Applicant Surname | Middleton |
Approval Committee | Internal Decision Panel |
Award Date | 2017-01-31T00:00:00+00:00 |
Financial Year | 2016/17 |
Grant Programme: Title | PhD Studentship (Basic) |
Internal ID | 109116/Z/15/A |
Lead Applicant | Mr Steven Middleton |
Partnership Value | 31040 |
Planned Dates: End Date | 2019-09-30T00:00:00+00:00 |
Planned Dates: Start Date | 2016-10-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | South East |