Background: Chemotherapy-induced peripheral neuropathy is a serious side effect in cancer treatment, a major manifestation being neuropathic pain that can be debilitating and can reduce the quality of life of the patient. Oxaliplatin and taxol are common anti-cancer drugs that induce neuropathic pain by an unknown mechanism. We tested the hypothesis that satellite glial cells in dorsal root ganglia (DRGs) are altered in chemotherapy-induced peripheral neuropathy models and contribute to neuropathic pain. Methods: Mice were injected with either oxaliplatin or taxol and examined at 7-30 days. Glial fibrillary acidic protein (glial activation marker) expression was determined by immunohistochemistry. Satellite glial cells in isolated DRG were injected with the fluorescent dye Lucifer yellow and the incidence of dye coupling among these cells that surround different neurons was quantified. Results: Taxol or oxaliplatin increased glial fibrillary acidic protein expression in satellite glial cells. Gap junction-mediated coupling between satellite glial cells was increased by up to fivefold after oxaliplatin and by up to twofold after taxol. This is consistent with work on other pain models showing that augmented satellite glial cell coupling contributes to chronic pain. Administration of the gap junction blocker carbenoxolone to chemotherapy-treated mice produced an analgesic-like effect. Conclusions: We propose that increased coupling by gap junctions is part of satellite glial cell activation, and that augmented coupling contributes to the lowering of pain threshold in oxaliplatin-and taxol-treated mice. We further propose that gap junction blockers may have potential in treating chemotherapy-induced neuropathic pain.

Stimulus characteristics of the mouse's visual field differ above and below the skyline. Here, we show for the first time that retinal ganglion cells (RGCs), the output neurons of the retina, gradually change their functional properties along the ventral-dorsal axis to allow better representation of the different stimulus characteristics. We conducted two-photon targeted recordings of transient-Offα-RGCs and found that they gradually became more sustained along the ventral-dorsal axis, revealing >5-fold-longer duration responses in the dorsal retina. Using voltage-clamp recordings, pharmacology, and genetic manipulation, we demonstrated that the primary rod pathway underlies this variance. Our findings challenge the current belief that RGCs of the same subtype exhibit the same light responses, regardless of retinal location, and suggest that networks underlying RGC responses may change with retinal location to enable optimized sampling of the visual image.

A retina completely devoid of topographic variations would be homogenous, encoding any given feature uniformly across the visual field. In a naive view, such homogeneity would appear advantageous. However, it is now clear that retinal topographic variations exist across mammalian species in a variety of forms and patterns. We briefly review some of the more established topographic variations in retinas of different mammalian species and focus on the recent discovery that cells belonging to a single neuronal subtype may exhibit distinct topographic variations in distribution, morphology, and even function. We concentrate on the mouse retina—originally viewed as homogenous—in which genetic labeling of distinct neuronal subtypes and other advanced techniques have revealed unexpected anatomical and physiological topographic variations. Notably, different subtypes reveal different patterns of nonuniformity, which may even be opposite or orthogonal to one another. These topographic variations in the encoding of visual space should be considered when studying visual processing in the retina and beyond. Expected final online publication date for the Annual Review of Vision Science, Volume 6 is September 15, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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