Medial Habenula Output Circuit Mediated by α5 Nicotinic Receptor-Expressing GABAergic Neurons in the Interpeduncular Nucleus
| Autor: | Aguan D. Wei, Lynne Tempest, Yun Wei A Hsu, Eric E. Turner, Lely A. Quina, Hongkui Zeng |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Habenula Interpeduncular nucleus Raphe General Neuroscience Mice Transgenic Articles Biology Receptors GABA-A Mice Inbred C57BL Mice Nicotinic acetylcholine receptor Organ Culture Techniques Nicotinic agonist Dorsal raphe nucleus Gene Expression Regulation Animals Cholinergic GABAergic Female GABAergic Neurons Nerve Net Cholinergic neuron Neuroscience Serotonergic Neurons |
| Zdroj: | The Journal of Neuroscience. 33:18022-18035 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2927-13.2013 |
| Popis: | TheChrna5gene encodes the α5 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, α5GFP, to examine the cellular phenotype, connectivity, and function of α5-expressing neurons. Although the medial habenula (MHb) has been proposed as a site of α5 function, α5GFPis not detectable in the MHb, and α5 mRNA is expressed there only at very low levels. However, α5GFPis 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 fluorescencein situhybridization reveals that these neurons are exclusively GABAergic. Transgenic and conventional tract tracing show that α5GFPneurons in the IP project principally to the MnR/PMnR and DTg/interfascicular dorsal raphe, both areas rich in serotonergic neurons. The α5GFPneurons 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 α5GFPIP neurons. Selective inhibitors of both α4β2- and α3β4-containing nicotinic receptors were able to reduce nicotine-evoked inward currents in α5GFPneurons in the IP, suggesting a mixed nicotinic receptor profile in these cells. Together, these findings show that the α5-GABAergic interneurons form a link from the MHb to serotonergic brain centers, which is likely to mediate some of the behavioral effects of nicotine. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|