Expression of the striatal DARPP-32/ARPP-21 phenotype in GABAergic neurons requires neurotrophins in vivo and in vitro

Sanja Ivkovic, Michelle E. Ehrlich

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

Abstract

The medium spiny neuron (MSN) is the major output neuron of the caudate nucleus and uses GABA as its primary neurotransmitter. A majority of MSNs coexpress DARPP-32 and ARPP-21, two dopamine and cyclic AMP-regulated phosphoproteins, and most of the matrix neurons express calbindin. DARPP-32 is the most commonly used MSN marker, but previous attempts to express this gene in vitro have failed. In this study we found that DARPP-32 is expressed in <12% of E13- or E17-derived striatal neurons when they are grown in defined media at high or low density in serum, dopamine, or Neurobasal/N2 (Life Technologies), and ARPP-21 is expressed in <1%. The percentage increases to 25% for DARPP-32 and 10% for ARPP-21 when the same cells are grown in Neurobasal/B27 (Life Technologies) for 7 d. After growth in Neurobasal/B27 plus brain-derived neurotrophic factor (BDNF) for 7 d, E13- derived MSNs are 53.7% DARPP-32-positive and 29.0% ARPP-21-positive; E17- derived MSNs are 66.8% DARPP-32-positive and 51.5% ARPP-21-positive. The percentage of calbindin-positive neurons also is increased under these conditions. Finally, ARPP-21 expression is reduced in mice with a targeted deletion of the BDNF gene. We conclude that BDNF is required for the maturation of a large subset of patch and matrix MSNs in vivo and in vitro. In addition, we introduce a culture system in which highly differentiated MSNs may be generated, maintained, and studied.

Original languageEnglish
Pages (from-to)5409-5419
Number of pages11
JournalJournal of Neuroscience
Volume19
Issue number13
DOIs
StatePublished - 1 Jul 1999
Externally publishedYes

Keywords

  • ARPP-21
  • Brain-derived neurotrophic factor
  • Calbindin
  • DARPP-32
  • Lateral ganglionic eminence
  • Striatum

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