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The Journal of Neuroscience, December 3, 2003, 23(35):11045-11053

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Cellular/Molecular
The 3 Nicotinic Receptor Subunit: A Component of -Conotoxin MII-Binding Nicotinic Acetylcholine Receptors that Modulate Dopamine Release and Related Behaviors

Changhai Cui,^1,6 * T. K. Booker,^1 * Roberta S. Allen,^1 * Sharon R. Grady,² Paul Whiteaker,² Michael J. Marks,² Outi Salminen,² Theresa Tritto,² Christopher M. Butt,² W. R. Allen,¹ Jerry A. Stitzel,³ J. Michael McIntosh,⁴ Jim Boulter,⁵ Allan C. Collins,² and Stephen F. Heinemann¹

¹Salk Institute for Biological Studies, La Jolla, California 92037, ²Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado 80309, ³Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109-0930, ⁴Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah 84112, ⁵Department Psychiatry and Biobehavioral Science, University of California Los Angeles, Los Angeles, California 90024, and ⁶Blanchette Rockefeller Neuroscience Institute, Rockville, Maryland 20850

Nigrostriatal dopaminergic neurons express many nicotinic acetylcholine receptor (nAChR) subunits capable of forming multiple nAChR subtypes. These subtypes are expressed differentially along the neuron and presumably mediate diverse responses. 3 subunit mRNA has restricted expression but is abundant in the substantia nigra and ventral tegmental areas. To investigate the potential role(s) of nicotinic receptors containing the 3 subunit in dopaminergic tracts, we generated mice with a null mutation in the 3 gene. We were thereby able to identify a population of 3-dependent -conotoxin MII-binding nAChRs that modulate striatal dopamine release. Changes were also observed in locomotor activity and prepulse inhibition of acoustic startle, behaviors that are controlled, in part, by nigrostriatal and mesolimbic dopaminergic activity, respectively, suggesting that 3-containing nAChRs modulate these behaviors.

Key words: 3 neuronal nicotinic receptor; gene knock-out; striatal dopamine release; -conotoxin MII; locomotor activity; prepulse inhibition of acoustic startle

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Received April 1, 2003; revised September 3, 2003; accepted September 5, 2003.

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