Establishing precise synaptic connections is crucial to the development of functional neural circuits. The direction-selective circuit in the retina relies upon highly selective wiring of inhibitory inputs from starburst amacrine cells1 (SACs) onto four subtypes of ON–OFF direction-selective ganglion cells (DSGCs), each preferring motion in one of four cardinal directions2. It has been reported in rabbit that the SACs on the ‘null’ sides of DSGCs form functional GABA (γ-aminobutyric acid)-mediated synapses, whereas those on the preferred sides do not3. However, it is not known how the asymmetric wiring between SACs and DSGCs is established during development. Here we report that in transgenic mice with cell-type-specific labelling, the synaptic connections from SACs to DSGCs were of equal strength during the first postnatal week, regardless of whether the SAC was located on the preferred or null side of the DSGC. However, by the end of the second postnatal week, the strength of the synapses made from SACs on the null side of a DSGC significantly increased whereas those made from SACs located on the preferred side remained constant. Blocking retinal activity by intraocular injections of muscimol or gabazine during this period did not alter the development of direction selectivity. Hence, the asymmetric inhibition between the SACs and DSGCs is achieved by a developmental program that specifically strengthens the GABA-mediated inputs from SACs located on the null side, in a manner not dependent on neural activity.
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We thank S. Nakanishi for mGluR2–GFP mice, A. Huberman for Drd4–GFP mice, J. Elstrott for help with MATLAB software, X. Han for mouse genotyping, J. Ledue for imaging assistance and A. Blankenship for reading the manuscript. This work was supported by grants RO1EY013528 and ARRA EY019498 from the National Institutes of Health.
The authors declare no competing financial interests.
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Wei, W., Hamby, A., Zhou, K. et al. Development of asymmetric inhibition underlying direction selectivity in the retina. Nature 469, 402–406 (2011). https://doi.org/10.1038/nature09600
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