Structural and functional consequences of a human nicotinic receptor mutation

Funded Activity Summary

Identification of the defective gene underlying a particular form of inherited epilepsy in man, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), now provides the first opportunity to study the basic mechanisms of an inherited epilepsy in man. The responsible mutations affect a subunit of the nicotinic acetylcholine receptor. In this research project, quantitative methods of imaging the brain will be used bridge the gap in understanding which lies between the molecular defect and the clinical manifestations of ADNFLE. Involvement of a system of nerve pathways, the mesocortical dopaminergic system, is postulated to explain the preferential susceptibility of the frontal lobe to seizures in ADNFLE. Positron emission tomography will be used to examine changes in neurotransmitter release in the frontal lobe. The molecular defect in ADNFLE also provides a unique opportunity to examine the role of the nicotinic receptor in the development of the human brain and in important aspects of human cognition. Statistical mapping of anatomical variability and high resolution magnetic resonance scans will be used to detect alterations in the anatomical structure of the mesial frontal lobe. Evidence of deficient nicotinic receptor-mediated cognitive effects in ADNFLE will be sought using a battery of psychological tests shown to be sensitive to the effects of nicotine.

Funded Activity Details

Start Date: 01-01-2000

End Date: 01-01-2001

Funding Scheme: NHMRC Project Grants

Funding Amount: $112,809.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Neurology And Neuromuscular Diseases

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

Brain development | Dopamine | Epilepsy | Genetics | Magnetic resonance imaging | Nicotinic receptor | Positron emission tomography | Smoking

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