Neuronal nicotinic acetylcholine receptors (nAChRs) are expressed throughout the central nervous system, and are active in a wide array of physiological phenomena including addiction, cognition, locomotion, autonomic function, and sensation. While a role for nAChRs in these activities is clear from the pharmacological action of cholinergic agonists, the physiological role of specific nAChR subtypes in these processes is often unresolved. Neuronal nAChRs are pentameric ion channels composed of a variety of alpha and beta subunits, and the specific subunit combination can have a dramatic impact on channel properties including agonist and antagonist selectivity profiles, as well as the kinetics of activation, inactivation, and desensitization. The proposed research plan describes a set of experiments designed to study nAChR subunit expression in dorsal root ganglia (DRG) and the spinal cord dorsal horn (SC). The experiments will also examine the physiological role of specific receptor subtypes in the modulation of nociceptive processing. Whole-cell patch clamp recordings of neurons will be used to characterize the functional nAChRs expressed in these cells. Corroborative evidence will come from single-cell RT-PCR analysis of mRNA expression in recorded neurons, as well as immunohistochemistry of neurons in culture and tissue slices. Finally, spinal cord slices and neuronal co-cultures will be used to directly assay the modulation of synaptic transmission between DRG and SC neurons.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30DA006033-03
Application #
6523243
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2002-08-15
Project End
Budget Start
2002-08-15
Budget End
2003-08-14
Support Year
3
Fiscal Year
2002
Total Cost
$51,179
Indirect Cost
Name
University of Chicago
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
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Genzen, Jonathan R; McGehee, Daniel S (2003) Short- and long-term enhancement of excitatory transmission in the spinal cord dorsal horn by nicotinic acetylcholine receptors. Proc Natl Acad Sci U S A 100:6807-12
Genzen, J R; Van Cleve, W; McGehee, D S (2001) Dorsal root ganglion neurons express multiple nicotinic acetylcholine receptor subtypes. J Neurophysiol 86:1773-82