Alpha7 nicotonic receptor actions on GABAergic synapses

Lead Research Organisation: University College London
Department Name: UNLISTED

Abstract

Nicotine derived from tobacco acts on receptors in the brain, which are normally activated by the endogenous neurotransmitter acetylcholine. Although nicotine abuse is an important cause of premature death and disease, activation of nicotinic receptors enhances cognitive performance. How it does so is not known. We have recently discovered a powerful effect of activation of a subtype of nicotinic receptors on inhibitory transmission in a subset of neurons in the brain. We propose to explore the underlying mechanisms, and to investigate the consequences of this phenomenon for network function.

Technical Summary

Alpha7 nicotinic receptors enhance performance in cognitive tests, but their cellular roles are poorly understood. We have found that GABAergic transmission in hippocampal interneurons is profoundly down-regulated by agonists of alpha7 receptors. This action involves a change in GABAA receptors, rather than a presynaptic alteration in GABA release. Synaptically released ACh mimics the effect of exogenous agonists. This proposal focuses on the cell-type specificity of this phenomenon, its molecular mechanisms, and its consequences for network function. Understanding how ACh acts on cortical circuits will help to identify potential routes to mitigate the effects of degenerative disorders that affect cholinergic pathways, in particular Alzheimer s disease, and may also shed light on the mechanisms of nicotine addiction.
 
Description ART pilot grant
Amount £29,167 (GBP)
Funding ID ART-PPG2009B-6 
Organisation Alzheimer's Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2010 
End 05/2010
 
Description ERC grant
Amount £2,300,000 (GBP)
Organisation European Research Council (ERC) 
Sector Public
Country Belgium
Start 10/2009 
End 09/2012
 
Description Innovator Award: Glutamate-gated chloride channel treatment of epilepsy
Amount £456,266 (GBP)
Funding ID 209807/Z/17/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2018 
End 09/2020
 
Title Interneuron collection 
Description Systematic database of interneuron properties 
Type Of Material Database/Collection of Data/Biological Samples 
Year Produced 2007 
Provided To Others? Yes  
Impact None yet 
 
Description Nicotinic Receptors in Alzheimers Disease 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Pilot data obtained
Collaborator Contribution Pilot data for MRC grant application
Impact grant application submitted
Start Year 2009
 
Description Online research news 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact Research advances in plasticity of inhibition have featured in online releases on the Institute of Neurology homepage.

Public contact
Year(s) Of Engagement Activity 2007