Visual signal pathway reorganization in the Cacna1f mutant rat model.

PURPOSE: To elucidate the underlying pathologic mechanism of congenital stationary night blindness (CSNB) by examining the characteristics of electrical signal transmission within the inner retinal circuit after Cacna1f gene mutation.

METHODS

Retinas isolated from the spontaneous Cacna1f mutant rats or wild-type rats were placed into a recording chamber, with the ganglion cell layer facing the biochip electrode array. The light-driven responses of the retinal ganglion cells (RCGs) were recorded using a multielectrode array (MEA) system. In the electrical stimulus cases, charge-balanced biphasic current pulse trains were generated and applied to the central electrode of MEA to stimulate the RCGs. Chemical compounds were bath-applied through an active perfusion system. The acquired data were further analyzed off-line.

RESULTS

Typical electrical responses were successfully recorded in the retinas of both wild-type rats and Cacna1f gene mutated rats. In the Cacna1f mutant retinas, the amplitude of the light-induced a-wave was decreased, paralleling the vanished b-wave. The responsive a-wave was not blocked by the application of 100 μM 2-amino-4-phosphobutyric acid. The increased spontaneous firing rate and the decreased robustness of light-driven signaling reflected a loss in the ability of ganglion cells to encode visual signals reliably and economically. Moreover, the ON pathway is somehow disconnected from ganglion cells, whereas OFF pathways may be preferentially selected by the CSNB retinas. In the electrical stimulus cases, the long-latency responses of RGCs evoked by the indirect synaptic inputs from outer layers of retina were weaker in the CSNB rats compared with that of SD rats.

CONCLUSIONS

Using MEA recording, we provide evidences of functional changes for visual signal pathway plasticity in the Cacna1f mutated retinas. Our results suggest that the dysfunctions in photoreceptor neurotransmitter release and the loss of signaling efficiency both occur during CSNB, and the latter is possibly reversible.