Influence of eye pigmentation on retinal degeneration in P23H and S334ter mutant rhodopsin transgenic rats.

Dark-rearing has been found to slow the rate of retinal degeneration in albino P23H but not S334ter mutant rhodopsin transgenic (Tg) rats. Since eye pigmentation has the same protective slowing effect as dark-rearing in RCS rats, we examined whether eye pigmentation has a comparable slowing effect in the different mutant rhodopsin Tg rats. Different lines of albino P23H and S334ter Tg rats on the Sprague-Dawley (SD) background were bred to Long-Evans (LE) rats to produce pigmented Tg rats. These were compared to albino Tg rats at postnatal days of different ages using the outer nuclear layer (ONL) as a morphological measure of photoreceptor number and electroretinogram (ERG) a- and b-wave amplitudes as a measure of retinal function. When compared to albino P23H rats, pigmented P23H rats had a slower rate of degeneration as measured by greater ONL thicknesses and greater ERG a- and b-wave amplitudes. By contrast, pigmented S334ter rats showed no difference in ONL thicknesses or ERG a- and b-wave amplitudes when compared to their albino equivalents. Thus, degeneration of photoreceptors in P23H Tg rats is slowed by eye pigmentation as measured by ONL thickness, while it is not in the S334ter Tg rats. Eye pigmentation also protects functional changes in ERG a- and b-waves for the P23H lines, but not for the S334ter lines.

Improving Robot Motor Learning with Negatively Valenced Reinforcement Signals.

Both nociception and punishment signals have been used in robotics. However, the potential for using these negatively valenced types of reinforcement learning signals for robot learning has not been exploited in detail yet. Nociceptive signals are primarily used as triggers of preprogrammed action sequences. Punishment signals are typically disembodied, i.e., with no or little relation to the agent-intrinsic limitations, and they are often used to impose behavioral constraints. Here, we provide an alternative approach for nociceptive signals as drivers of learning rather than simple triggers of preprogrammed behavior. Explicitly, we use nociception to expand the state space while we use punishment as a negative reinforcement learning signal. We compare the performance-in terms of task error, the amount of perceived nociception, and length of learned action sequences-of different neural networks imbued with punishment-based reinforcement signals for inverse kinematic learning. We contrast the performance of a version of the neural network that receives nociceptive inputs to that without such a process. Furthermore, we provide evidence that nociception can improve learning-making the algorithm more robust against network initializations-as well as behavioral performance by reducing the task error, perceived nociception, and length of learned action sequences. Moreover, we provide evidence that punishment, at least as typically used within reinforcement learning applications, may be detrimental in all relevant metrics.

Discordant anatomical, electrophysiological, and visual behavioral profiles of retinal degeneration in rat models of retinal degenerative disease.

PURPOSE: To assess structural, functional, and visual behavioral relationships in mutant rhodopsin transgenic (Tg) rats and to determine whether early optokinetic tracking (OKT) visual experience, known to permanently elevate visual thresholds in normal rats, can enhance vision in rats with photoreceptor degeneration. METHODS: Eight lines of pigmented Tg rats and RCS rats were used in this study. OKT thresholds were tested at single ages (1, 2, 3, 4, and 6 months) in naïve groups of rats, or daily in groups that began at eye-opening (P15) or 10 days later (P25). Electroretinogram (ERG) response amplitudes were recorded after OKT testing, and outer nuclear layer (ONL) thickness measurements were then obtained. RESULTS: OKT thresholds, when measured at a single time point in naïve Tg lines beginning at P30, did not decline until months after significant photoreceptor loss. Daily testing of Tg lines resulted mostly with OKT thresholds inversely related to photoreceptor degeneration, with rapid degenerations resulting in sustained OKT thresholds for long periods despite the rapid photoreceptor loss. Slower degenerations resulted in rapid decline of thresholds, long before the loss of most photoreceptors, which was even more pronounced when daily testing began at eye opening. This amplified loss of function was not a result of testing-induced damage to the rod or cone photoreceptors, as ERG amplitudes and ONL thicknesses were the same as untested controls. CONCLUSIONS: The unexpected lack of correlation of OKT testing with photoreceptor degeneration in the Tg rats emphasizes the need in behavioral therapeutic studies for careful analysis of visual thresholds of experimental animals prior to therapeutic intervention.