Molecular and Physiological Diversity of Nicotinic Acetylcholine Receptors in the Midbrain Dopaminergic Nuclei

J Neurosci. 2001 Mar 1;21(5):1452-63. doi: 10.1523/JNEUROSCI.21-05-01452.2001.

Abstract

Nicotinic acetylcholine receptors (nAChRs) on dopaminergic (DA) and GABAergic (Gaba) projection neurons of the substantia nigra (SN) and ventral tegmental area (VTA) are characterized by single-cell RT-PCR and patch-clamp recordings in slices of rat and wild-type, beta2-/-, alpha4-/-, and alpha7-/- mice. The eight nAChR subunits expressed in these nuclei, alpha3-7 and beta2-4, contribute to four different types of nAChR-mediated currents. Most DA neurons in the SN and VTA express two nAChR subtypes. One is inhibited by dihydro-beta-erythroidine (2 microm), alpha-conotoxin MII (10 nm), and methyllycaconitine (1 nm) but does not contain the alpha7 subunit; it possesses a putative alpha4alpha6alpha5(beta2)(2) composition. The other subtype is inhibited by dihydro-beta-erythroidine (2 microm) and has a putative alpha4alpha5(beta2)(2) composition. Gaba neurons in the VTA exhibit a third subtype with a putative (alpha4)(2)(beta2)(3) composition, whereas Gaba neurons in the SN have either the putative (alpha4)(2)(beta2)(3) oligomer or the putative alpha4alpha6alpha5(beta2)(2) oligomer. The fourth subtype, a putative (alpha7)(5) homomer, is encountered in less than half of DA and Gaba neurons, in the SN as well as in the VTA. Neurons in the DA nuclei thus exhibit a diversity of nAChRs that might differentially modulate reinforcement and motor behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine / metabolism*
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / metabolism
  • In Vitro Techniques
  • Mice
  • Mice, Mutant Strains
  • Microinjections
  • Neurons / classification
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Antagonists / administration & dosage
  • Patch-Clamp Techniques
  • Protein Subunits
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Nicotinic / deficiency
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism*
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism*
  • alpha7 Nicotinic Acetylcholine Receptor
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Chrna7 protein, mouse
  • Chrna7 protein, rat
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Protein Subunits
  • RNA, Messenger
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • nicotinic acetylcholine receptor alpha4 subunit
  • nicotinic receptor beta2
  • gamma-Aminobutyric Acid
  • Tyrosine 3-Monooxygenase
  • Glutamate Decarboxylase
  • Dopamine