Advancing understanding of anaesthesia and analgesia in the zebrafish
Award Number
BB/V000411/1Status / Stage
ActiveDates
1 September 2021 -31 August 2024
Duration (calculated)
02 years 11 monthsFunder(s)
BBSRC (UKRI)Funding Amount
£576,085.00Funder/Grant study page
BBSRC UKRIContracted Centre
University of ExeterPrincipal Investigator
Professor Charles TylerPI Contact
C.R.Tyler@exeter.ac.ukWHO Catergories
Understanding Underlying DiseaseDisease Type
Dementia (Unspecified)CPEC Review Info
| Reference ID | 729 |
|---|---|
| Researcher | Reside Team |
| Published | 07/07/2023 |
Data
| Award Number | BB/V000411/1 |
|---|---|
| Status / Stage | Active |
| Start Date | 20210901 |
| End Date | 20240831 |
| Duration (calculated) | 02 years 11 months |
| Funder/Grant study page | BBSRC UKRI |
| Contracted Centre | University of Exeter |
| Funding Amount | £576,085.00 |
Abstract
Each year millions of embryonic and larval (embryo-larval) zebrafish are used globally in laboratories, many of which undergo anaesthesia. Despite this, little information is available to guide anaesthetic or analgesic choices for fish, with even less data available for embryo-larvae. This knowledge gap is extensive, spanning an absence of basic information on appropriate dosing concentrations, to a lack of knowledge of the central circuitry involved in sedation or nociception. This project will fill these knowledge gaps via 3 main aims. Aim 1 will establish the efficacy of several anaesthetics/analgesics using functional brain imaging and electrophysiology. For the functional imaging we have developed a technique using zebrafish with pan-neuronally-expressed GCaMP6s that allows us to quantify brain-region specific responses to stimulation under conditions of anaesthesia and analgesia. Concentrations required to induce euthanasia will be confirmed using electrophysiology. Aim 2 will determine which agents inhibit neuromuscular activity, are aversive, or reduce avoidance of noxious stimuli using automated behavioural assessment. This includes quantifying the avoidance of each agent using a tank arena place preference assay for aversion, and the effect of analgesics on the amelioration of noxious simulation for nociception. Aim 3 is focussed on understanding mechanisms of action and central sedative and nociceptive processing in fish. For this we will undertake functional imaging in circuit-specific transgenic reporter lines and supplement this with immunohistochemistry to identify specific circuits responding to treatment with these agents. The same approach will be used following noxious stimulation in order to define the central circuitry involved in nociception, which is largely unknown in fish. This project will provide data to refine millions of animal experiments, and generate important mechanistic information on anaesthetic and analgesic action in fish.
Aims
Aim 1 will establish the efficacy of several anaesthetics/analgesics using functional brain imaging and electrophysiology. Aim 2 will determine which agents inhibit neuromuscular activity, are aversive, or reduce avoidance of noxious stimuli using automated behavioural assessment. Aim 3 is focussed on understanding mechanisms of action and central sedative and nociceptive processing in fish.