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Mikhail Y. Lipin, Robert G. Smith; GABAB Receptors Control GABA and Acetylcholine Release in the Direction Selective Pathway. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3032.
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© ARVO (1962-2015); The Authors (2016-present)
The retinal direction selective ganglion cell (DSGC) responds preferentially to motion in one direction. The crucial role in directional selectivity belongs to starburst amacrine cells (SBACs), which release acetylcholine to excite DSGCs, and GABA to inhibit DSGCs and bipolar cells. It has been suggested that the morphological properties of the SBAC generate DS that is amplified by intrinsic or network properties. One possibility for network enhancement of DS is that some bipolar cells are known to express GABAB receptors, which are negatively coupled to calcium channels, and thus control glutamate release. Other possibilities for enhancement of DS are modulation of GABA/acetylcholine release from SBACs by GABAB receptors, or glutamate release from bipolar cells by GABAC receptors. To find out how GABAB and GABAC receptors affect direction selectivity, we studied light responses of the DSGC under GABAB or GABAC block.
We used in vitro whole-mount retinas from Hartley guinea pigs anesthetized with pentobarbital. The retinas (n=5) were maintained in Ames medium at 35ºC. We recorded voltage-clamped responses of On-Off DSGCs to a moving dark bar (40% contrast, 3000µm by 120µm, moving on its longest axis) with velocity 2000 µm/s. We applied conductance analysis to distinguish the excitatory and inhibitory inputs. To block GABAB receptors, we applied 3 µM CGP52432. To block GABAC receptors, we applied 50 µM TPMPA. To separate glutamatergic and cholinergic inputs to the DSGC, we blocked nicotinic receptors with 100 µM of hexamethonium and 30 nM methyllycaconitine.
Block of GABAB receptors potentiated Off- excitatory and inhibitory inputs to the DSGC by ~2-fold in 3 out of 5 DSGCs, hardly affecting On- excitation and inhibition. To test whether GABAB receptors directly affected glutamate release from bipolar cells, we blocked GABAB receptors in the presence of nicotinic receptor antagonists. In this case, GABAB receptor block moderately decreased (by 20%) both Off- and On- excitatory inputs to the DSGC. In a separate experiment, GABAC block potentiated excitation to the DSGC by 30% with or without nicotinic block.
These results imply that GABAC receptors control glutamatergic excitation to the DSGC, but that GABAB receptors control its Off- inhibition and cholinergic excitation. This represents an essential asymmetry between On- and Off- direction selective pathways.
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