a6-Containing nicotinic @entity934 receptors in midbrain XXXX neurons are poised to govern @entity935 -mediated behaviors and synaptic plasticity.

@entity286 @entity935 @entity19 @entity71 @entity1239 @entity191 @entity161 @entity3451 @entity15683 @entity934
UNASSIGNED: @entity934 ( @entity3451 ) acts through nicotinic and muscarinic @entity3451 receptors in the ventral midbrain and striatal areas to influence @entity935 (DA) transmission. This cholinergic control of DA transmission is important for processes such as attention and motivated behavior, and is manipulated by @entity1239 in @entity286 products. Identifying and characterizing the key @entity3451 receptors involved in cholinergic control of DA transmission could lead to small molecule therapeutics for treating disorders involving @entity71 , @entity191 , and @entity161 . a6-Containing nicotinic @entity934 receptors (nAChRs) are highly and specifically expressed in midbrain DA neurons, making them an attractive drug target. Here, we used genetic, pharmacological, behavioral, and biophysical approaches to study this @entity15683 subtype. For many experiments, we used @entity19 expressing mutant a6 nAChRs ("a6L9S" @entity19 ) that increase the sensitivity of these receptors to agonists such as @entity3451 and @entity1239 . Taking advantage of a simple behavioral phenotype exhibited by a6L9S @entity19 , we compared the ability of full versus partial a6(   ) @entity15683 agonists to activate a6(   ) nAChRs in vivo. Using local infusions of both agonists and antagonists into the brain, we demonstrate that neurons and nAChRs in the midbrain are sufficient to account for this behavioral response. To complement these behavioral studies, we studied the ability of in vivo a6(   ) @entity15683 activation to support plasticity changes in midbrain DA neurons that are relevant to behavioral sensitization and addiction. By coupling local infusion of drugs and brain slice patch-clamp electrophysiology, we show that activating a6(   ) nAChRs in midbrain DA areas is sufficient to enhance glutamatergic transmission in ventral tegmental area (VTA) DA neurons. Together, these results from in vivo studies strongly suggest that a6(   ) nAChRs expressed by VTA DA neurons are positioned to strongly influence both DA-mediated behaviors and the induction of synaptic plasticity by @entity1239 .
