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Ccl5 Mediates Proper Wiring of Feedforward and Lateral Inhibition Pathways in the Inner Retina
Journal article   Open access   Peer reviewed

Ccl5 Mediates Proper Wiring of Feedforward and Lateral Inhibition Pathways in the Inner Retina

D’Anne S. Duncan, Rebecca L. Weiner, Carl Weitlauf, Michael L. Risner, Abigail L. Roux, Emily R. Sanford, Cathryn R. Formichella and Rebecca M. Sappington
Frontiers in neuroscience, Vol.12, pp.702-702
10/12/2018
DOI: 10.3389/fnins.2018.00702
PMCID: PMC6194164
PMID: 30369865
url
https://doi.org/10.3389/fnins.2018.00702View
Published (Version of record) Open Access

Abstract

The β-chemokine Ccl5 and its receptors are constitutively expressed in neurons of the murine inner retina. Here, we examined the functional and structural significance of this constitutive Ccl5 signaling on retinal development. We compared outcomes of electrophysiology, ocular imaging and retinal morphology in wild-type mice (WT) and mice with Ccl5 deficiency ( Ccl5 -/- ). Assessment of retinal structure by ocular coherence tomography and histology revealed slight thinning of the inner plexiform layer (IPL) and inner nuclear layer (INL) in Ccl5 -/- mice, compared to WT ( p < 0.01). Assessment of postnatal timepoints important for development of the INL (P7 and P10) revealed Ccl5-dependent alterations in the pattern and timing of apoptotic pruning. Morphological analyses of major inner retinal cell types in WT, Ccl5 -/- , gustducin gfp and gustducin gfp / Ccl5 -/- mice revealed Ccl5-dependent reduction in GNAT3 expression in rod bipolar cells as well as a displacement of their terminals from the IPL into the GCL. RGC dendritic organization and amacrine cell morphology in the IPL was similarly disorganized in Ccl5 -/- mice. Examination of the intrinsic electrophysiological properties of RGCs revealed higher spontaneous activity in Ccl5 -/- mice that was characterized by higher spiking frequency and a more depolarized resting potential. This hyperactive phenotype could be negated by current clamp and correlated with both membrane resistance and soma area. Overall, our findings identify Ccl5 signaling as a mediator of inner retinal circuitry during development of the murine retina. The apparent role of Ccl5 in retinal development further supports chemokines as trophic modulators of CNS development and function that extends far beyond the inflammatory contexts in which they were first characterized.
 amacrine cell bipolar cell Ccl5 chemokine gustducin Neuroscience PKCα retinal ganglion cell

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