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Differential modulation by nicotine of substantia nigra versus ventral tegmental area dopamine neurons.
J Neurophysiol. 2007 Dec; 98(6):3388-96.JN

Abstract

Midbrain dopamine (DA) neurons are found in two nuclei, the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). The SNc dopaminergic projections to the dorsal striatum are involved in voluntary movement and habit learning, whereas the VTA projections to the ventral striatum contribute to reward and motivation. Nicotine induces profound DA release from VTA dopamine neurons but substantially less from the SNc. Nicotinic acetylcholine receptor (nAChR) expression differs between these nuclei, but it is unknown whether there are differences in nAChR expression on the afferent projections to these nuclei. Here we have compared the nicotinic modulation of excitatory and inhibitory synaptic inputs to VTA and SNc dopamine neurons. Although nicotine enhances both the excitatory and inhibitory drive to SNc DA cells with response magnitudes similar to those seen in the VTA, the prevalence of these responses in SNc is much lower. We also found that a mixture of nAChR subtypes underlies the synaptic modulation in SNc, further distinguishing this nucleus from the VTA, where alpha7 nAChRs enhance glutamate inputs and non-alpha7 receptors enhance GABA inputs. Finally, we compared the nicotine sensitivity of DA neurons in these two nuclei and found larger response magnitudes in VTA relative to SNc. Thus the observed differences in nicotine-induced DA release from VTA and SNc are likely due to differences in nAChR expression on the afferent inputs as well as on the DA neurons themselves. This may explain why nicotine has a greater effect on behaviors associated with the VTA than the SNc.

Authors+Show Affiliations

Department of Neurobiology, Pharmacology, Physiology, University of Chicago, Chicago, IL 60637, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17942622

Citation

Keath, J Russel, et al. "Differential Modulation By Nicotine of Substantia Nigra Versus Ventral Tegmental Area Dopamine Neurons." Journal of Neurophysiology, vol. 98, no. 6, 2007, pp. 3388-96.
Keath JR, Iacoviello MP, Barrett LE, et al. Differential modulation by nicotine of substantia nigra versus ventral tegmental area dopamine neurons. J Neurophysiol. 2007;98(6):3388-96.
Keath, J. R., Iacoviello, M. P., Barrett, L. E., Mansvelder, H. D., & McGehee, D. S. (2007). Differential modulation by nicotine of substantia nigra versus ventral tegmental area dopamine neurons. Journal of Neurophysiology, 98(6), 3388-96.
Keath JR, et al. Differential Modulation By Nicotine of Substantia Nigra Versus Ventral Tegmental Area Dopamine Neurons. J Neurophysiol. 2007;98(6):3388-96. PubMed PMID: 17942622.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential modulation by nicotine of substantia nigra versus ventral tegmental area dopamine neurons. AU - Keath,J Russel, AU - Iacoviello,Michael P, AU - Barrett,Lindy E, AU - Mansvelder,Huibert D, AU - McGehee,Daniel S, Y1 - 2007/10/17/ PY - 2007/10/19/pubmed PY - 2008/3/6/medline PY - 2007/10/19/entrez SP - 3388 EP - 96 JF - Journal of neurophysiology JO - J. Neurophysiol. VL - 98 IS - 6 N2 - Midbrain dopamine (DA) neurons are found in two nuclei, the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). The SNc dopaminergic projections to the dorsal striatum are involved in voluntary movement and habit learning, whereas the VTA projections to the ventral striatum contribute to reward and motivation. Nicotine induces profound DA release from VTA dopamine neurons but substantially less from the SNc. Nicotinic acetylcholine receptor (nAChR) expression differs between these nuclei, but it is unknown whether there are differences in nAChR expression on the afferent projections to these nuclei. Here we have compared the nicotinic modulation of excitatory and inhibitory synaptic inputs to VTA and SNc dopamine neurons. Although nicotine enhances both the excitatory and inhibitory drive to SNc DA cells with response magnitudes similar to those seen in the VTA, the prevalence of these responses in SNc is much lower. We also found that a mixture of nAChR subtypes underlies the synaptic modulation in SNc, further distinguishing this nucleus from the VTA, where alpha7 nAChRs enhance glutamate inputs and non-alpha7 receptors enhance GABA inputs. Finally, we compared the nicotine sensitivity of DA neurons in these two nuclei and found larger response magnitudes in VTA relative to SNc. Thus the observed differences in nicotine-induced DA release from VTA and SNc are likely due to differences in nAChR expression on the afferent inputs as well as on the DA neurons themselves. This may explain why nicotine has a greater effect on behaviors associated with the VTA than the SNc. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/17942622/Differential_modulation_by_nicotine_of_substantia_nigra_versus_ventral_tegmental_area_dopamine_neurons_ L2 - http://www.physiology.org/doi/full/10.1152/jn.00760.2007?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -