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Title of project or programme
| Title of PI | Nicotine action on neuronal networks of the prefrontal cortex: targets for cognitive enhancement in neuropsychiatric disorders |
Principal Investigators of project/programme grant
| Title | Forname | Surname | Institution | Country |
| Dr | Huibert | Mansvelder | Vrije Universiteit Amsterdam, Center for Neurogenomics and Cognitive Research | Netherlands |
Address of institution of lead PI
| Institution | Vrije Universiteit Amsterdam, Center for Neurogenomics and Cognitive Research |
| Street Address | De Boelelaan 1015 |
| City | Amsterdam |
| Postcode | 1082 SB |
Country
- Netherlands
Source of funding information
Netherlands Organisation for Health Research and Development (ZonMw)
Total sum awarded (Euro)
600000
Start date of award
15-12-2006
Total duration of award in months
60
The project/programme is most relevant to
- Neurodegenerative disease in general
Keywords
Nicotine, Alzheimer’s disease, Parkinson’s disease, schizophrenia and ADHD, neuronal and synaptic mechanisms
Research abstract in English
Nicotine has been shown to improve cognitive function in humans. Nicotinic treatments are being developed as therapy for cognitive dysfunction in patients suffering from neuropsychiatric disorders such as Alzheimer’s disease, Parkinson’s disease, schizophrenia and ADHD. Critical for development of nicotinic therapeutics is an understanding of neuronal and synaptic mechanisms underlying nicotinic involvement in cognitive function. Nicotinic agonists act beneficial on several aspects of cognition including working memory, attention, learning and memory. Different brain areas and different nicotinic receptors are involved in these effects. Little is known of how nicotine enhances attention function and we understand little of the cellular and synaptic mechanisms involved. With the research proposed here, I aim to resolve which nicotinic receptor subtypes are involved in improving attention function and understand neuronal and synaptic mechanisms underlying this cognition enhancement in prefrontal cortex (PFC), which is involved in attention.
Nicotine also improves cognitive performance in primates and rodents. I will study short- and long-term effects mediated by different nicotinic receptor types on synaptic and cellular properties of neuronal networks in mouse PFC, using a combination of two-photon imaging and electrophysiology in living brain slices. To assess roles of distinct receptor types in modulating PFC circuitry and attention behaviour I will use transgenic mice with genetically altered functionality of specific nicotinic receptor subunits. I will study how nicotinic modulation of neuronal and synaptic activity is affected when a specific receptor subunit is lacking. By re-expression of specific subunits selectively in PFC of knock out mice lacking that particular subunit with lentiviral vectors, I will examine whether nicotinic modulation of neuronal networks and behavioural attention performance is restored. This research will increase our understanding of how nicotine acts as cognitive enhancer and identify specific nicotinic receptors as target for therapeutic treatments of patients suffering from cognitive dysfunction.
Lay Summary
In which category does this research fall?
- Basic research
Nicotine action on neuronal networks of the prefrontal cortex: targets for cognitive enhancement in neuropsychiatric disorders
Investments > €500k
Netherlands
Neurodegenerative disease in general
2011