The Journal of Neuroscience, February 4, 2004, 24(5):1023-1033; doi:10.1523/JNEUROSCI.3936-03.2004
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Cellular/Molecular
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, and
Vadim Yakhnitsa
Neurological Sciences Institute, Oregon Health and Science University, Beaverton, Oregon 97006
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
1-subunit of the GABAA receptor, as determined by a yeast two-hybrid technique. This interaction was confirmed by coimmunoprecipitation of ACBP and the
1-subunit of the GABAA receptor using an antibody to GABAA
1. The interaction was also confirmed by a "pull-down" assay in which histidine-tagged ACBP was used to pull down the GABAA
1. ACBP does not cross the bloodbrain 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.
Key words: adaptation; astrocyte (astroglia); diazepam; glia; nystagmus; retina
Received Nov 20, 2003;
revised November 20, 2003;
accepted November 21, 2003.