Purchase this article with an account.
Arash Ng, Erin Zampaglione, Peter Fuerst, Robert Burgess, Alan Litke, David Feldheim, Alexander Sher; DSCAM is required for functional retinal circuitry. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2497.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Retinal ganglion cells (RGCs) of the same type form non-random mosaics that can be observed by the regular spacing of cell bodies and tiling of dendritic fields. Mosaics have also been observed functionally, by the regular spacing of receptive fields. The anatomical mosaics have been shown to require cell adhesion molecules, one of which is DSCAM. In the absence of DSCAM, same type RGC somas and dendrites clump. Here we investigated if DSCAM is involved in establishing the functional properties of the RGCs using large-scale multielectrode arrays to measure light evoked responses.
An isolated retina was flattened RGC side down over the MEA. White noise and drifting sqaurewave stimuli were focused on the photoreceptors to evoke light responses in the retina. RGC responses were recorded. Cells were classified by spatio-temporal response properties. The spike triggered average (STA), the average stimulus presented to an RGC’s receptive field prior to firing an action potential, was used to characterize the spatial receptive field. Direction selective RGCs (DSRGCs) were identified as those that respond strongly in a preferred direction and weakly in the null direction.
DSCAM knockout mice retain certain aspects of retinal function. ON and OFF type RGCs were identified. However, DSCAM knockout RGCs have longer response latencies. Same type RGC receptive fields no longer form non-random mosaics in the DSCAM knockout retinas. Fewer DSRGCs were identified, and out of those DSRGCs, direction selective responses were weaker when compared to wild-type DSRGCs.
Our results indicate that anatomical features in the retina determine the functional properties of the circuits. This confirms that cell adhesion molecules also play a role in shaping the response properties of neurons in the retina. The observed clumping of receptive fields in the DSCAM knockout is similar to the anatomical phenotype suggesting that the position of an RGC determines the connectivity of that RGC to the interneurons. Dendritic clumping may result in abnormal number and types of inputs the RGC receives. Altered connectivity can affect the ability to generate direction selective responses, as DSRGCs depend on their specific synaptic connections in the inner plexiform layer. Our approach can be extended to probe circuitry development and function.
This PDF is available to Subscribers Only