科研之友
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摘要
Nicotinic acetylcholine receptors (nAChRs) containing alpha 6 subunits are expressed in only a few brain areas, including midbrain dopamine (DA) neurons, noradrenergic neurons of the locus ceruleus, and retinal ganglion cells. To better understand the regional and subcellular expression pattern of alpha 6-containing nAChRs, we created and studied transgenic mice expressing a variant alpha 6 subunit with green fluorescent protein (GFP) fused in-frame in the M3-M4 intracellular loop. In alpha 6-GFP transgenic mice, alpha 6-dependent synaptosomal DA release and radioligand binding experiments confirmed correct expression and function in vivo. In addition to strong alpha 6(star) nAChR expression in glutamatergic retinal axons, which terminate in superficial superior colliculus (sSC), we also found alpha 6 subunit expression in a subset of GABAergic cell bodies in this brain area. In patch-clamp recordings from sSC neurons in brain slices from mice expressing hypersensitive alpha 6(star) nAChRs, we confirmed functional, postsynaptic alpha 6(star) nAChR expression. Further, sSC GABAergic neurons expressing alpha 6(star) nAChRs exhibit a tonic conductance mediated by standing activation of hypersensitive alpha 6(star) nAChRs by ACh. alpha 6(star) nAChRs also appear in a subpopulation of SC neurons in output layers. Finally, selective activation of alpha 6(star) nAChRs in vivo induced sSC neuronal activation as measured with c-Fos expression. Together, these results demonstrate that alpha 6(star) nAChRs are uniquely situated to mediate cholinergic modulation of glutamate and GABA release in SC. The SC has emerged as a potential key brain area responsible for transmitting short-latency salience signals to thalamus and midbrain DA neurons, and these results suggest that alpha 6(star) nAChRs may be important for nicotinic cholinergic sensitization of this pathway.
- 出版日期2012-7-25
