TY - JOUR
T1 - Development of the vertebrate retinal direction-selective circuit
AU - Hamilton, Natalie R.
AU - Scasny, Andrew J.
AU - Kolodkin, Alex L.
N1 - Funding Information:
We thank Rebecca James, Marla Feller, Samer Hattar, Andrew Huberman, John Hunyara and anonymous reviewers for helpful comments on this manuscript. All Figure illustrations were drawn by N.R.H. Work in the authors' laboratory is supported in part by the National Eye Institute / NIH . N.R.H is supported by the National Science Foundation Graduate Research Fellowship Program (NSF GRFP).
Funding Information:
When, and how, is asymmetric SAC input onto DSGCs formed during development? Two landmark studies established that for both ON-OFF DSGCs and ON DSGCs, asymmetric inhibition from SACs arises during the second postnatal week during a relatively narrow window between ?~ ?P6 and P8 (Wei et al., 2011; Yonehara et al., 2011). This asymmetry is independent of both spontaneous activity and visual experience, since direction selectivity arises prior to eye opening (at P13) and pharmacological blockade of activity from P6?P12 does not alter the direction-selectivity of DSGCs. During the first postnatal week, the somas of SACs synaptically connected to DSGCs are equally distributed between the null and preferred side of DSGC dendritic arbors. Further, at P6 the spatial distribution and strength of inhibitory synapses onto both ON-OFF DSGCs and ON DSGCs is also symmetric. However, at P8, SACs located on the null side of these DSGCs elicit greater inhibitory currents than those on the preferred side, and at P14, GABAergic conductances are higher when elicited from depolarization of null side SACs than from the preferred (Wei et al., 2011; Yonehara et al., 2011). Direct support for the conclusions drawn from these observations comes from experiments combining two-photon calcium imaging with serial block-face EM, revealing that SACs on the null side of DSGC dendrites form a greater number of inhibitory synapses onto DSGCs than those on the preferred side (Briggman et al., 2011).The importance of proximal dendritic orientation supports the idea that asymmetric connectivity between SACs and DSGCs is driven by synaptogenic cues that are selectively trafficked to a specific quadrant of the SAC arbor and that recognize a subtype-specific partner in the DSGC arbor, with these cues being distributed such that antiparallel orientations of SAC proximal dendrites and DSGC PDs are preferred. Rather than requiring detection of the local orientation of each distal dendritic segment and sending out the appropriate molecule, correct distribution of such cues could be achieved by sorting at the soma-dendrite border. The search for the molecular determinants of asymmetric connectivity, therefore, should benefit from focusing on identifying sets of proteins localized to specific quadrants of the SAC arbor and complementary cues, perhaps CAMs, with expression limited to a specific DSGC subtype.We thank Rebecca James, Marla Feller, Samer Hattar, Andrew Huberman, John Hunyara and anonymous reviewers for helpful comments on this manuscript. All Figure illustrations were drawn by N.R.H. Work in the authors' laboratory is supported in part by the National Eye Institute/NIH. N.R.H is supported by the National Science Foundation Graduate Research Fellowship Program (NSF GRFP).
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/9
Y1 - 2021/9
N2 - The vertebrate retina contains an array of neural circuits that detect distinct features in visual space. Direction-selective (DS) circuits are an evolutionarily conserved retinal circuit motif – from zebrafish to rodents to primates – specialized for motion detection. During retinal development, neuronal subtypes that wire DS circuits form exquisitely precise connections with each other to shape the output of retinal ganglion cells tuned for specific speeds and directions of motion. In this review, we follow the chronology of DS circuit development in the vertebrate retina, including the cellular, molecular, and activity-dependent mechanisms that regulate the formation of DS circuits, from cell birth and migration to synapse formation and refinement. We highlight recent findings that identify genetic programs critical for specifying neuronal subtypes within DS circuits and molecular interactions essential for responses along the cardinal axes of motion. Finally, we discuss the roles of DS circuits in visual behavior and in certain human visual disease conditions. As one of the best-characterized circuits in the vertebrate retina, DS circuits represent an ideal model system for studying the development of neural connectivity at the level of individual genes, cells, and behavior.
AB - The vertebrate retina contains an array of neural circuits that detect distinct features in visual space. Direction-selective (DS) circuits are an evolutionarily conserved retinal circuit motif – from zebrafish to rodents to primates – specialized for motion detection. During retinal development, neuronal subtypes that wire DS circuits form exquisitely precise connections with each other to shape the output of retinal ganglion cells tuned for specific speeds and directions of motion. In this review, we follow the chronology of DS circuit development in the vertebrate retina, including the cellular, molecular, and activity-dependent mechanisms that regulate the formation of DS circuits, from cell birth and migration to synapse formation and refinement. We highlight recent findings that identify genetic programs critical for specifying neuronal subtypes within DS circuits and molecular interactions essential for responses along the cardinal axes of motion. Finally, we discuss the roles of DS circuits in visual behavior and in certain human visual disease conditions. As one of the best-characterized circuits in the vertebrate retina, DS circuits represent an ideal model system for studying the development of neural connectivity at the level of individual genes, cells, and behavior.
KW - Circuit
KW - Direction selectivity
KW - Retina
KW - Visual system
UR - http://www.scopus.com/inward/record.url?scp=85107930550&partnerID=8YFLogxK
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U2 - 10.1016/j.ydbio.2021.06.004
DO - 10.1016/j.ydbio.2021.06.004
M3 - Article
C2 - 34118273
AN - SCOPUS:85107930550
SN - 0012-1606
VL - 477
SP - 273
EP - 283
JO - Developmental Biology
JF - Developmental Biology
ER -