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Functional nicotinic acetylcholine receptors containing α6 subunits are on GABAergic neuronal boutons adherent to ventral tegmental area dopamine neurons.
J Neurosci. 2011 Feb 16; 31(7):2537-48.JN

Abstract

Diverse nicotinic acetylcholine receptor (nAChR) subtypes containing different subunit combinations can be placed on nerve terminals or soma/dendrites in the ventral tegmental area (VTA). nAChR α6 subunit message is abundant in the VTA, but α6*-nAChR cellular localization, function, pharmacology, and roles in cholinergic modulation of dopaminergic (DA) neurons within the VTA are not well understood. Here, we report evidence for α6β2*-nAChR expression on GABA neuronal boutons terminating on VTA DA neurons. α-Conotoxin (α-Ctx) MII labeling coupled with immunocytochemical staining localizes putative α6*-nAChRs to presynaptic GABAergic boutons on acutely dissociated, rat VTA DA neurons. Functionally, acetylcholine (ACh) induces increases in the frequency of bicuculline-, picrotoxin-, and 4-aminopyridine-sensitive miniature IPSCs (mIPSCs) mediated by GABA(A) receptors. These increases are abolished by α6*-nAChR-selective α-Ctx MII or α-Ctx PIA (1 nm) but not by α7 (10 nm methyllycaconitine) or α4* (1 μm dihydro-β-erythroidine)-nAChR-selective antagonists. ACh also fails to increase mIPSC frequency in VTA DA neurons prepared from nAChR β2 knock-out mice. Moreover, ACh induces an α-Ctx PIA-sensitive elevation in intraterminal Ca(2+) in synaptosomes prepared from the rat VTA. Subchronic exposure to 500 nm nicotine reduces ACh-induced GABA release onto the VTA DA neurons, as does 10 d of systemic nicotine exposure. Collectively, these results indicate that α6β2*-nAChRs are located on presynaptic GABAergic boutons within the VTA and modulate GABA release onto DA neurons. These presynaptic α6β2*-nAChRs likely play important roles in nicotinic modulation of DA neuronal activity.

Authors+Show Affiliations

Division of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013-4496, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21325521

Citation

Yang, Kechun, et al. "Functional Nicotinic Acetylcholine Receptors Containing Α6 Subunits Are On GABAergic Neuronal Boutons Adherent to Ventral Tegmental Area Dopamine Neurons." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 31, no. 7, 2011, pp. 2537-48.
Yang K, Buhlman L, Khan GM, et al. Functional nicotinic acetylcholine receptors containing α6 subunits are on GABAergic neuronal boutons adherent to ventral tegmental area dopamine neurons. J Neurosci. 2011;31(7):2537-48.
Yang, K., Buhlman, L., Khan, G. M., Nichols, R. A., Jin, G., McIntosh, J. M., Whiteaker, P., Lukas, R. J., & Wu, J. (2011). Functional nicotinic acetylcholine receptors containing α6 subunits are on GABAergic neuronal boutons adherent to ventral tegmental area dopamine neurons. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 31(7), 2537-48. https://doi.org/10.1523/JNEUROSCI.3003-10.2011
Yang K, et al. Functional Nicotinic Acetylcholine Receptors Containing Α6 Subunits Are On GABAergic Neuronal Boutons Adherent to Ventral Tegmental Area Dopamine Neurons. J Neurosci. 2011 Feb 16;31(7):2537-48. PubMed PMID: 21325521.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional nicotinic acetylcholine receptors containing α6 subunits are on GABAergic neuronal boutons adherent to ventral tegmental area dopamine neurons. AU - Yang,Kechun, AU - Buhlman,Lori, AU - Khan,Ghous M, AU - Nichols,Robert A, AU - Jin,Guozhang, AU - McIntosh,J Michael, AU - Whiteaker,Paul, AU - Lukas,Ronald J, AU - Wu,Jie, PY - 2011/2/18/entrez PY - 2011/2/18/pubmed PY - 2011/4/2/medline SP - 2537 EP - 48 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 31 IS - 7 N2 - Diverse nicotinic acetylcholine receptor (nAChR) subtypes containing different subunit combinations can be placed on nerve terminals or soma/dendrites in the ventral tegmental area (VTA). nAChR α6 subunit message is abundant in the VTA, but α6*-nAChR cellular localization, function, pharmacology, and roles in cholinergic modulation of dopaminergic (DA) neurons within the VTA are not well understood. Here, we report evidence for α6β2*-nAChR expression on GABA neuronal boutons terminating on VTA DA neurons. α-Conotoxin (α-Ctx) MII labeling coupled with immunocytochemical staining localizes putative α6*-nAChRs to presynaptic GABAergic boutons on acutely dissociated, rat VTA DA neurons. Functionally, acetylcholine (ACh) induces increases in the frequency of bicuculline-, picrotoxin-, and 4-aminopyridine-sensitive miniature IPSCs (mIPSCs) mediated by GABA(A) receptors. These increases are abolished by α6*-nAChR-selective α-Ctx MII or α-Ctx PIA (1 nm) but not by α7 (10 nm methyllycaconitine) or α4* (1 μm dihydro-β-erythroidine)-nAChR-selective antagonists. ACh also fails to increase mIPSC frequency in VTA DA neurons prepared from nAChR β2 knock-out mice. Moreover, ACh induces an α-Ctx PIA-sensitive elevation in intraterminal Ca(2+) in synaptosomes prepared from the rat VTA. Subchronic exposure to 500 nm nicotine reduces ACh-induced GABA release onto the VTA DA neurons, as does 10 d of systemic nicotine exposure. Collectively, these results indicate that α6β2*-nAChRs are located on presynaptic GABAergic boutons within the VTA and modulate GABA release onto DA neurons. These presynaptic α6β2*-nAChRs likely play important roles in nicotinic modulation of DA neuronal activity. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/21325521/Functional_nicotinic_acetylcholine_receptors_containing_α6_subunits_are_on_GABAergic_neuronal_boutons_adherent_to_ventral_tegmental_area_dopamine_neurons_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=21325521 DB - PRIME DP - Unbound Medicine ER -