Postnatal Development of Tyrosine Hydroxylase mRNA-expressing Neurons in Mouse Neostriatum

Eur J Neurosci. 2011 Nov;34(9):1355-67. doi: 10.1111/j.1460-9568.2011.07873.x. Epub 2011 Oct 17.


The striatum harbors a small number of tyrosine hydroxylase (TH) mRNA-containing GABAergic neurons that express TH immunoreactivity after dopamine depletion, some of which reportedly resembled striatal medium spiny projection neurons (MSNs). To clarify whether the TH mRNA-expressing neurons were a subset of MSNs, we characterized their postnatal development of electrophysiological and morphological properties using a transgenic mouse strain expressing enhanced green fluorescent protein (EGFP) under the control of the rat TH gene promoter. At postnatal day (P)1, EGFP-TH+ neurons were present as clusters in the striatum and, thereafter, gradually scattered ventromedially by P18 without regard to the striatal compartments. They were immunonegative for calbindin, but immunopositive for enkephalin (54.5%) and dynorphin (80.0%). Whole-cell patch-clamp recordings revealed at least two distinct neuronal types, termed EGFP-TH+ Type A and B. Whereas Type B neurons were aspiny and negative for the MSN marker dopamine- and cyclic AMP-regulated phosphoprotein of 32 kDa (DARPP-32), Type A neurons constituted 75% of the EGFP+ cells, had dendritic spines (24.6%), contained DARPP-32 (73.6%) and a proportion acquired TH immunoreactivity after injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 3-nitropropionic acid. The membrane properties and N-methyl-d-aspartate : non-N-methyl-d-aspartate excitatory postsynaptic current ratio of Type A neurons were very similar to MSNs at P18. However, their resting membrane potentials and spike widths were statistically different from those of MSNs. In addition, the calbindin-like, DARPP-32-like and dynorphin B-like immunoreactivity of Type A neurons developed differently from that of MSNs in the matrix. Thus, Type A neurons closely resemble MSNs, but constitute a cell type distinct from classical MSNs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • Age Factors
  • Animals
  • Animals, Newborn
  • Bromodeoxyuridine / metabolism
  • Calbindins
  • Choline O-Acetyltransferase / metabolism
  • Dopamine Agents / pharmacology
  • Dopamine and cAMP-Regulated Phosphoprotein 32 / metabolism
  • Dynorphins / metabolism
  • Enkephalins / metabolism
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology*
  • Glutamate Decarboxylase / metabolism
  • Green Fluorescent Proteins
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Neostriatum / cytology*
  • Neostriatum / drug effects
  • Neostriatum / growth & development*
  • Neurons / classification
  • Neurons / metabolism*
  • Neuropeptides / metabolism
  • Nitric Oxide Synthase / metabolism
  • Patch-Clamp Techniques
  • RNA, Messenger / metabolism*
  • Rats
  • S100 Calcium Binding Protein G / metabolism
  • Tubulin / metabolism
  • Tyrosine 3-Monooxygenase / genetics*


  • Calbindins
  • Dopamine Agents
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • Enkephalins
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Ppp1r1b protein, mouse
  • RNA, Messenger
  • S100 Calcium Binding Protein G
  • Tubulin
  • beta3 tubulin, mouse
  • doublecortin protein
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Dynorphins
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Nitric Oxide Synthase
  • Tyrosine 3-Monooxygenase
  • Choline O-Acetyltransferase
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1
  • Bromodeoxyuridine