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Compensation in the primary rod pathway following partial rod loss in the mature retina

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Abstract Number: 4785

AuthorBlock: Rachel Care1, Ivan Anastassov2, Felice Dunn1
1UCSF, San Francisco, California, United States; 2Department of Biology, San Francisco State University, San Francisco, California, United States;

DisclosureBlock: Rachel Care, None; Ivan Anastassov, None; Felice Dunn, None;

Understanding the function of the deafferented mature retinal circuit is critical for therapeutic efforts to rescue its function. Extensive work in models of rod degenerations has demonstrated the capacity of the developing retina to compensate for input loss, but little is known about whether this capacity extends beyond development. Here we induce partial rod death in mature retina and measure function throughout the rod pathway to identify potential sites of compensation.

We expressed the diphtheria toxin receptor (DTR) under the rhodopsin promoter (iRho-Cre) and partially ablated the rod population with diphtheria toxin injection at postnatal day 30 (Control: 7.3 ± 2.2; DTR: 4.5 ± 0.6 rows of rod cell bodies, p<0.005). To measure the functional output of the mature retina after partial rod loss, we made cell-attached and whole-cell patch-clamp recordings from alpha ON-sustained ganglion cells (AON-S GC) in ventral retina. We presented 10msec flashes of blue light or UV light on a blue mean to selectively stimulate either rods or cones, respectively. To understand the excitatory pathway leading to these ganglion cells, we made whole-cell voltage- and current-clamp recordings from rod bipolar cells in retinal slices.

After partial rod loss, the intensity response function of AON-S GC spiking showed increased sensitivity (Control: 9.03 ± 8.9, n=5; DTR: 2.7 ± 1.5 Rh*/rod, n=7; p=0.017). However, there was no change in the sensitivity of the excitatory currents onto these cells (Control: 6.42 ± 3.9, n=5; DTR: 5.74 ± 11.5 Rh*/rod, n=7; p=1). Similarly, whole-cell recordings in rod bipolar cells showed no difference in the sensitivity of the excitatory currents onto these cells after partial rod loss (Control: 4.36 ± 1.8, n=18; DTR: 4.81 ± 2.1 Rh*/rod, n=9; p=0.78).

These findings indicate that mature retina can compensate for partial rod loss. Our data suggest that one site of compensation is the current-to-spike generation within AON-S GCs. Because the sensitivity of their spiking response was greater than the sensitivity of the excitatory currents that drive this response, we conclude that these cells increase their excitability after partial rod loss. Our results also suggest that compensation occurs at the rod-to-rod bipolar synapse because at the level of excitatory currents onto rod bipolar cells, the circuit’s sensitivity has already recovered from partial rod loss.

Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details.
Massive photoreceptor death as occurs in diseases like rod dystrophies eventually leads to loss of vision, but the reaction of the remaining circuitry is not well understood. We used genetic tools in the mouse to elucidate the functional consequences of rod death in adult retina and found evidence for functional compensation in the first synapse and in the retinal output cells. Our results will aid in the application of therapies for vision loss and add to our understanding of plasticity in an acutely perturbed mature neural circuit.