Are striatal tyrosine hydroxylase interneurons dopaminergic?

Harry S. Xenias, Osvaldo Ibáñez-Sandoval, Tibor Koós, James M. Tepper*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Striatal GABAergic interneurons that express the gene for tyrosine hydroxylase (TH) have been identified previously by several methods. Although generally assumed to be dopaminergic, possibly serving as a compensatory source of dopamine (DA) in Parkinson’s disease, this assumption has never been tested directly. In TH–Cre mice whose nigrostriatal pathway had been eliminated unilaterally with 6-hydroxydopamine, we injected a Cre-dependent virus coding for channelrhodopsin-2 and enhanced yellow fluorescent protein unilaterally into the unlesioned midbrain or bilaterally into the striatum. Fast-scan cyclic voltammetry in striatal slices revealed that both optical and electrical stimulation readily elicited DA release in control striata but not from contralateral striata when nigrostriatal neurons were transduced. In contrast, neither optical nor electrical stimulation could elicit striatal DA release in either the control or lesioned striata when the virus was injected directly into the striatum transducing only striatal TH interneurons. This demonstrates that striatalTHinterneurons do not release DA. Fluorescence immunocytochemistry in enhanced green fluorescent protein (EGFP)–TH mice revealed colocalization of DA, L-amino acid decarboxylase, the DA transporter, and vesicular monoamine transporter-2 with EGFP in midbrain dopaminergic neurons but not in any of the striatal EGFP–TH interneurons. Optogenetic activation of striatal EGFP–TH interneurons produced strong GABAergic inhibition in all spiny neurons tested. These results indicate that striatal TH interneurons are not dopaminergic but rather are a type of GABAergic interneuron that expresses TH but none of the other enzymes or transporters necessary to operate as dopaminergic neurons and exert widespread GABAergic inhibition onto direct and indirect spiny neurons.

Original languageEnglish (US)
Pages (from-to)6584-6599
Number of pages16
JournalJournal of Neuroscience
Volume35
Issue number16
DOIs
StatePublished - Apr 22 2015
Externally publishedYes

Keywords

  • Dopamine
  • GABA
  • Interneuron
  • Neostriatum
  • Optogenetics
  • Voltammetry

ASJC Scopus subject areas

  • Neuroscience(all)

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