Activity-Dependent Expression of Acyl-Coenzyme A-Binding Protein in Retinal Muller Glial Cells Evoked by Optokinetic Stimulation

Neal H. Barmack, Timothy R. Bilderback, Henry Liu, Zuyuan Qian, Vadim Yakhnitsa

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Long-term horizontal optokinetic stimulation (HOKS) decreases the gain of the horizontal optokinetic reflex and evokes the second phase of optokinetic afternystagmus (OKAN-II). We investigated the possible molecular constituents of this adaptation. We used a differential display reverse transcriptase-PCR screen for mRNAs isolated from retinas of rabbits that received HOKS. In each rabbit, we compared mRNAs from the retina stimulated in the posterior→ anterior (preferred) direction with mRNAs from the retina stimulated in the anterior→posterior (null) direction. Acyl-CoA-binding protein (ACBP) mRNA was one of four mRNAs selected by this screen, the proteins of which interact with GABA receptors. HOKS in the preferred direction increased ACBP mRNA transcription and ACBP protein expression. ACBP was localized to Muller glial cells by hybridization histochemistry and by immunohistochemistry. ACBP interacts with the α1-subunit of the GABAA receptor, as determined by a yeast two-hybrid technique. This interaction was confirmed by coimmunoprecipitation of ACBP and the α1-subunit of the GABAA receptor using an antibody to GABAAα 1. The interaction was also confirmed by a "pull-down" assay in which histidine-tagged ACBP was used to pull down the GABA Aα1. ACBP does not cross the blood-brain barrier. However, smaller truncated proteolytic fragments of ACBP do, increasing the excitability of central cortical neurons. Muller cells may secrete ACBP in the inner plexiform layer, thereby decreasing the sensitivity of GABAA receptors expressed on the surface of ganglion cell dendrites. Because retinal directional sensitivity is linked to GABAergic transmission, HOKS-induced expression of ACBP could provide a molecular basis for adaptation to HOKS and for the genesis of OKAN-II.

Original languageEnglish (US)
Pages (from-to)1023-1033
Number of pages11
JournalJournal of Neuroscience
Volume24
Issue number5
DOIs
StatePublished - Feb 4 2004

    Fingerprint

Keywords

  • Adaptation
  • Astrocyte (astroglia)
  • Diazepam
  • Glia
  • Nystagmus
  • Retina

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this