| First Author | Hsu YW | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 46 | Pages | 18022-35 |
| PubMed ID | 24227714 | Mgi Jnum | J:250514 |
| Mgi Id | MGI:6100386 | Doi | 10.1523/JNEUROSCI.2927-13.2013 |
| Citation | Hsu YW, et al. (2013) Medial habenula output circuit mediated by alpha5 nicotinic receptor-expressing GABAergic neurons in the interpeduncular nucleus. J Neurosci 33(46):18022-35 |
| abstractText | The Chrna5 gene encodes the alpha5 nicotinic acetylcholine receptor subunit, an "accessory" subunit of pentameric nicotinic receptors, that has been shown to play a role in nicotine-related behaviors in rodents and is genetically linked to smoking behavior in humans. Here we have used a BAC transgenic mouse line, alpha5(GFP), to examine the cellular phenotype, connectivity, and function of alpha5-expressing neurons. Although the medial habenula (MHb) has been proposed as a site of alpha5 function, alpha5(GFP) is not detectable in the MHb, and alpha5 mRNA is expressed there only at very low levels. However, alpha5(GFP) is strongly expressed in a subset of neurons in the interpeduncular nucleus (IP), median raphe/paramedian raphe (MnR/PMnR), and dorsal tegmental area (DTg). Double-label fluorescence in situ hybridization reveals that these neurons are exclusively GABAergic. Transgenic and conventional tract tracing show that alpha5(GFP) neurons in the IP project principally to the MnR/PMnR and DTg/interfascicular dorsal raphe, both areas rich in serotonergic neurons. The alpha5(GFP) neurons in the IP are located in a region that receives cholinergic fiber inputs from the ventral MHb, and optogenetically assisted circuit mapping demonstrates a monosynaptic connection between these cholinergic neurons and alpha5(GFP) IP neurons. Selective inhibitors of both alpha4beta2- and alpha3beta4-containing nicotinic receptors were able to reduce nicotine-evoked inward currents in alpha5(GFP) neurons in the IP, suggesting a mixed nicotinic receptor profile in these cells. Together, these findings show that the alpha5-GABAergic interneurons form a link from the MHb to serotonergic brain centers, which is likely to mediate some of the behavioral effects of nicotine. |
