Abstract

The use of sensory information to drive specific behaviors relies on circuits spanning long distances that wire up through a range of axon-target recognition events. Mechanisms assembling poly-synaptic circuits and the extent to which parallel pathways can "cross-wire" to compensate for loss of one another remain unclear and are crucial to our understanding of brain development and models of regeneration. In the visual system, specific retinal ganglion cells (RGCs) project to designated midbrain targets connected to downstream circuits driving visuomotor reflexes. Here, we deleted RGCs connecting to pupillary light reflex (PLR) midbrain targets and discovered that axon-target matching is tightly regulated. RGC axons of the eye-reflex pathway avoided vacated PLR targets. Moreover, downstream PLR circuitry is maintained; hindbrain and peripheral components retained their proper connectivity and function. These findings point to a model in which poly-synaptic circuit development reflects independent, highly stringent wiring of each parallel pathway and downstream station.

Highlights

  • Based on their close positioning, high degree of axon-target specificity across multiple synapses, and defined, highly quantifiable behavioral outputs, these two circuits carry many of the qualities essential for probing development of parallel pathway assembly and for understanding how downstream circuits are impacted by disruptions of different nodes along each pathway

  • Even when OPN and mdPPN are rendered devoid of their normal retinal input, the axons of slow-DSGCs destined for eye movement centers continue to avoid pupillary light reflex (PLR) targets

  • Light-Intensity-Dependent Influences on PLR Behavior in ipRGC-Deficient Mice We examined the functional output of retinal-OPN connections in cKOs and found that the effect of losing luminance-sensing input on PLR was dependent on light intensity

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Summary

Graphical Abstract

Seabrook et al found using conditional genetic deletion of specific retinal ganglion cell types that retinal innervation of the pretectum is highly regulated and that downstream circuit connections are maintained following removal of peripheral sensory drive. Seabrook et al, 2017, Cell Reports 21, 3049–3064 December 12, 2017 a 2017 The Author(s).

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