The Role of NMDA Receptor Activity in Retinal Ganglion Cell Dendrite Development

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This abstract was presented today at the 2014 Association for Research in Vision and Opthalmology (ARVO) meetings in Orlando, Florida by Eerik M. Elias, Ping Wang and Ning Tian.

Full size poster available here.

Purpose: To elucidate mechanisms underlying the dendrite developmental plasticity of retinal ganglion cells, we examined the role of glutamate receptors on retinal ganglion cell dendrite elongation and filopodia elimination.

Methods: We used the JamB genetically labeled subtype of RGCs as our working model. JamB-CreER:YFP ganglion cell dendritic arbors were imaged in whole mount retina using confocal microscopy. Dendrite length, area, branching, and filopodia number were traced and measured using Neurolucida. Visual inputs were blocked by dark-rearing pups after P5. Glutamatergic activity was blocked using daily intraocular injections of AP5 and CNQX from P9 to P13 or genetic ablation of the NMDA receptor in these RGCs.

Results: To test the role of visual inputs on dendrite development, we dark-reared mice from P5 to P30 and found a modest effect on filopodia elimination in JamB RGCs. Anticipating that spontaneous glutamatergic activity in the retina may also contribute to RGC filopodia elimination, we blocked spontaneous glutamatergic activity by daily intraocular injections of AP5 and CNQX from P9 to P13. This led to an increase in filopodia density due to decreased dendrite length but no change in filopodia number. We confirmed this result by examining NMDAR knockout JamB cells (JamB-CreER:YFP:Grin1-/-). As expected, Grin1-/- JamB RGCs have decreased dendrite outgrowth like the pharmacologic blockade. However, filopodia elimination in these cells was significantly decreased as well, suggesting that NMDA and non-NMDA glutamate receptors might regulate the RGC dendritic development in a differential manner. This effect was dramatic at P13. To test if this effect persists into adulthood, we examined Grin1-/- JamB RGCs at P30 and found that they are indistinguishable from wild-type JamB RGCs, suggesting that a compensatory mechanism exists to drive dendrite elongation and filopodia elimination in the absence of the NMDA receptor.

Conclusions: Our study demonstrated that ganglion cell dendrite outgrowth and pruning of filopodia require glutamatergic activity and visual input that act via NMDA and possibly non-NMDA glutamate receptors.

Missing optomotor head turning reflex in the DBA/2J mouse

This paper by Peter Barabas, Wei Huang, Hui Chen, Christopher L. Koehler, Gareth Howell, Simon W.M. John, Ning Tian, René C Rentería and David Križaj is an outcome of an attempt to follow glaucoma progression in the DBA/2J mouse model of a naturally occurring, late onset form of glaucoma.  Ideally, a non-invasive technique should be used and in this case, they used a device to take advantage of the optomotor head turning reflex to assess progressive loss of vision.  This reflex is very similar to the involuntary rotation of the eye in response to a rotating visual stimulus and it is present in all animals from fish to mammals (including humans).  Interestingly, the DBA/2J strain was found to utterly lack this reflex.

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Who’s That? Ning Tian

This is the first photograph in a new category, “Who’s That?”, a evolving compendium of found imagery from years back of vision scientists.  The idea is that on occasion, one runs across imagery of vision scientists from other times and it makes for a compelling look back at history.  At the 2007 ARVO, Don Fox helped set up a presentation on the early years of ARVO where he showed some images of John Dowling, George Wald, Brian Boycott and more while Bob BarlowJohn Dowling and Harris Ripps spoke for almost two hours about the early history of ARVO and neuroscience research at the Marine Biology Lab at Woods Hole.

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An Instructive Role for Patterned Spontaneous Retinal Activity in Mouse Visual Map Development

This paper by Hongping Xu, Moran Furman, Yann S. Mineur, Hui Chen, Sarah L. King, David Zenisek, Z. Jimmy Zhou, Daniel A. Butts, Ning Tian, Marina R. Picciotto and Michael Crair describes a collaborative effort from several laboratories from Yale University, the University of Maryland and the University of Utah.  Two former postdoctoral fellows from the laboratory of Ning Tian, Drs. Hongping Xu (the first author) and Hui Chen, were principal contributors. Continue reading “An Instructive Role for Patterned Spontaneous Retinal Activity in Mouse Visual Map Development”

Effect of General Anesthetics on IOP in Elevated IOP Mouse Model

Elevated intraocular pressure (IOP) is the best recognized risk factor for the pathogenesis of glaucoma and the extent of retinal ganglion cell (RGC) degeneration in glaucoma is closely correlated with the extent of IOP elevation.  Therefore, accurately and reliably measuring IOP is critical in investigating the mechanism of pressure-induced RGC damage in glaucoma.  However, IOP is typically measured under general anesthesia in most studies using mouse models and many anesthetics affect the IOP measurements in both human and animals. Continue reading “Effect of General Anesthetics on IOP in Elevated IOP Mouse Model”

Light-Evoked Synaptic Activity of Retinal Ganglion and Amacrine Cells is Regulated in Developing Mouse Retina

This paper by Q. He, Wang P and Ning Tian characterizes the developmental profiles of the light evoked excitatory and inhibitory synaptic inputs from ON and OFF synaptic pathways in the retina, the light evoked synaptic outputs and the sensitivity of the light evoked synaptic inputs and outputs to light deprivation of retinal ganglion cells (RGCs) and displaced amacrine cells (ACs) of developing mouse retina.  The results strongly suggest that spontaneous and light-evoked synaptic activities of RGCs and ACs are regulated by different synaptic mechanisms.

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