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Christine M Emnett, Peter D Lukasiewicz; Dopamine acts presynaptically to suppress GABA-ergic mediated lateral inhibition to rod bipolar cells in mouse retina.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):115.
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© 2017 Association for Research in Vision and Ophthalmology.
Dopamine (DA) is known to facilitate the shift from rod (high sensitivity, low acuity) to cone (low sensitivity, high acuity) signaling during adaption in the mammalian retina. The precise effects of dopamine on network adaptation in the inner retina are unclear. During light adaptation, γ-amino-butyric acid (GABA) mediated lateral inhibition onto RBCs decreases. Does dopamine modulate (GABA) receptor responsiveness or does it modulate GABA release? Here we describe how dopamine suppresses the release of GABA from amacrine cells (ACs) onto rod bipolar cell (RBC) terminals.
Mouse RBCs were recorded using whole cell voltage clamp techniques in (200 or 400 micron) thick retina slices. RBCs were morphologically identified by dye. GABA receptor activity was directly measured by puffing GABA onto RBC terminals. GABAergic inhibitory post-synaptic currents (IPSCs) were evoked by activation of ACs with either AMPA puffs or light. All experiments that did not involve light-evoked responses were conducted in the light when dopamine is naturally saturating.
We show that dopamine has no direct effect on GABARs on RBC terminals. We blocked D1 receptors with SCH-23390 in WT slices and found no effect on GABA-puff mediated currents. Similarly, GABA responses were also unaffected by application of the dopamine agonist, ADTN, in slices prepared from retina specific tyrosine hydroxylase (Thy1) conditional knockout mice, which do not produce retinal dopamine. However, antagonism of D1 receptors in WT slices significantly increased the level of lateral inhibition evoked by AMPA in the IPL. Further, ADTN suppresses light-evoked IPSCs in dark-adapted slices. Thus, dopamine modulation altered evoked GABA-IPSCs, without affecting GABAR responsiveness.
Our findings suggest that dopamine suppresses GABA-mediated inhibition in RBC terminals by modulating GABA release from ACs. We previously showed that RBC GABAR mediated inhibition was suppressed by increasing light illumination. Our data provide a mechanistic framework for this finding and suggest that increasing dopamine levels suppress GABAR inhibition. Our results offer new insights into the molecular mechanisms of network adaptation in the mammalian retina.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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