Biomedical subjects

Glen T Prusky

Publications and source records attributed to Glen T Prusky.

9 recordsLinked to original sources

PubMed2006

Enhancement of vision by monocular deprivation in adult mice.

Plasticity of vision mediated through binocular interactions has been reported in mammals only during a "critical" period in juvenile life, wherein monocular deprivation (MD) causes an enduring loss of visual acuity (amblyopia) selectively through the deprived eye. Here, we report a different form of interocular plasticity of vision in adult mice in which MD leads to an enhancement of the optokinetic response (OKR) selectively through the nondeprived eye. Over 5 d of MD, the spatial frequency sensitivity of the OKR increased gradually, reaching a plateau of approximately 36% above pre-deprivation baseline. Eye opening initiated a gradual decline, but sensitivity was maintained above pre-deprivation baseline for 5-6 d. Enhanced function was restricted to the monocular visual field, notwithstanding the dependence of the plasticity on binocular interactions. Activity in visual cortex ipsilateral to the deprived eye was necessary for the characteristic induction of the enhancement, and activity in visual cortex contralateral to the deprived eye was necessary for its maintenance after MD. The plasticity also displayed distinct learning-like properties: Active testing experience was required to attain maximal enhancement and for enhancement to persist after MD, and the duration of enhanced sensitivity after MD was extended by increasing the length of MD, and by repeating MD. These data show that the adult mouse visual system maintains a form of experience-dependent plasticity in which the visual cortex can modulate the normal function of subcortical visual pathways.

Animals↗

PubMed2006

Cognitive deficits in rats after forebrain cholinergic depletion are reversed by a novel NO mimetic nitrate ester.

Many conditions adversely affecting learning, memory, and cognition are associated with reductions in forebrain acetylcholine (ACh), most notably aging and Alzheimer's disease. In the current study, we demonstrate that bilateral depletion of neocortical and hippocampal ACh in rats produces deficits in a spatial learning task and in a recently described, delayed visual matching-to-sample task. Oral administration of the novel nitrate, GT1061 (4-methyl-5-(2-nitroxyethyl) thiazole HCl), and the acetylcholinesterase inhibitor, donepezil, reversed the cognitive deficits in both memory tasks in a dose-dependent manner. GT1061 was superior in the delayed matching-to-sample task. GT1061 was absorbed rapidly after oral administration, crossed the blood brain barrier, and achieved brain concentrations that were slightly higher than those found in plasma. The activity of GT1061 was NO mimetic: soluble guanylyl cyclase (sGC) was activated, but selectivity was observed for sGC in the hippocampus relative to the vasculature; and hippocampal levels of phosphorylated ERK1/2, which is a postulated intermediary in the formation of long-term memory, were increased. The beneficial effect on visual and spatial memory task performance supports the concept that stimulating the NO/sGC/cGMP signal transduction system can provide new, effective treatments for cognitive disorders. This approach may be superior to that of current drugs that attempt only to salvage the residual function of damaged cholinergic neurons.

Acetylcholine↗

PubMed2005

Seahorse wins all races: hippocampus participates in both linear and non-linear visual discrimination learning.

Consistent with configural/conjunctive theories of the hippocampus, we report that rats trained on the non-linear transverse patterning discrimination problem (A+ versus B-, B+ versus C-, and C+ versus A) displayed retrograde amnesia when the hippocampus was later damaged. They also failed to relearn the solution to this problem. Damage to the hippocampus following training also produced retrograde amnesia in rats trained on a set of elemental discrimination problems (A+ versus B-, C+ versus D-, and E+ versus F-) that could be solved based on the associative strengths of the individual choice cues. However, in contrast to transverse patterning, rats easily relearned and retained these elemental problems and learned a new set of elemental problems after the damage. These results support two theoretical conclusions: (a) elemental discriminations can be learned by both a system that depends on the hippocampus and a system that does not require the hippocampus, and (b) in the intact animal these two systems competitively interact with the hippocampal-dependent system inhibiting memory formation by the extra-hippocampal system.

Animals↗

PubMed2004

Recovery of cortical binocularity and orientation selectivity after the critical period for ocular dominance plasticity.

Cortical binocularity is abolished by monocular deprivation (MD) during a critical period of development lasting from approximately postnatal day (P) 35 to P70 in ferrets. Although this is one of the best-characterized models of neural plasticity and amblyopia, very few studies have examined the requirements for recovery of cortical binocularity and orientation selectivity of deprived eye responses. Recent studies indicating that different mechanisms regulate loss and recovery of binocularity raise the possibility that different sensitive periods characterize loss and recovery of deprived eye responses. In this report, we have examined whether the potential for recovery of binocularity and orientation selectivity is restricted to the critical period. Quantitative single unit recordings revealed recovery of cortical binocularity and full recovery of orientation selectivity of deprived eye responses following prolonged periods of MD (i.e., >3 wk) starting at P49, near the peak of plasticity. Surprisingly, recovery was present when binocular vision was restored after the end of the critical period for ocular dominance plasticity, as late as P83. In contrast, ferrets that had never received visual experience through the deprived eye failed to recover binocularity even though normal binocular vision was restored at P50, halfway through the critical period. Collectively, these results indicate that there is potential for recovery of cortical binocularity and deprived eye orientation selectivity after the end of the critical period for ocular dominance plasticity.

Animals↗

PubMed2004

Damage to the hippocampal formation does not disrupt representational flexibility as measured by a novelty transfer test.

Rats were trained on a set of visual discrimination problems (A+B-, C+D-, E+F-). The choice stimuli were then recombined to create novel combination tests (A+D-, C+F-, E+B-). Rats with damage to the hippocampus showed perfect transfer on these tests, always choosing A, C, and E, but were not able to learn the spatial location of the platform, indicating that damage to the hippocampus was functional. These results question the generality of H. Eichenbaum, P. Mathews, and N. J. Cohen's (1989) findings and the theoretical claim that choice behavior with novel combinations is based on inferential-like hippocampus-dependent processes (H. Eichenbaum, 1992). They are consistent with the view that simple associative processes guide choice behavior in animals with hippocampal damage that are confronted with novel combinations.

Animals↗

PubMed2004

Quantification of spatial vision in the Royal College of Surgeons rat.

PURPOSE: To examine how spatial vision deteriorates in the RCS rat over time as a background to experimental studies aimed at limiting photoreceptor degeneration. METHODS: The Visual Water Task was used to quantify the grating acuity of pigmented dystrophic RCS rats as they aged and to compare both grating acuity and contrast sensitivity in nondystrophic RCS rats with those parameters in normal pigmented laboratory rats (Long-Evans). RESULTS: Nondystrophic rats had grating acuities and contrast sensitivity functions that were similar to those obtained from Long-Evans rats. The grating acuity of dystrophic rats deteriorated from 80% of normal at 1 month of age to blindness by 11 months. Acuity declined rapidly to 0.32 cyc/deg over the first 4 months, with a slower decline thereafter. CONCLUSIONS: Robust measures of vision can be achieved in RCS rats using the Visual Water Task, and with this test, no visual dysfunction can be detected in the background strain. The course of functional deterioration in dystrophic rats is highly predictable, allowing the approach to be used to explore the substrates of the deterioration in vision and to monitor the effects of therapeutic retinal interventions on spatial vision.

Aging↗

PubMed2004

Rapid quantification of adult and developing mouse spatial vision using a virtual optomotor system.

PURPOSE: To develop a simple, rapid method of quantifying the spatial vision of mice. METHODS: A rotating cylinder covered with a vertical sine wave grating was calculated and drawn in virtual three-dimensional (3-D) space on four computer monitors facing to form a square. C57BL/6 mice standing unrestrained on a platform in the center of the square tracked the grating with reflexive head and neck movements. The spatial frequency of the grating was clamped at the viewing position by repeatedly recentering the cylinder on the head. Acuity was quantified by increasing the spatial frequency of the grating until an optomotor response could not be elicited. Contrast sensitivity was measured at spatial frequencies between 0.03 and 0.35 cyc/deg. RESULTS: Grating acuity was measurable on the day of eye opening (postnatal day [P]15: mean acuity, 0.031 cyc/deg) and reached a maximum (approximately 0.4 cyc/deg) by P24. A peak in the contrast sensitivity function emerged on P16 (4.7, or 21% contrast at 0.064 cyc/deg). The peak remained at 0.064 cyc/deg and climbed to a maximum sensitivity of 24.5, or 4% contrast, by P29. Acuity was obtained in each mouse in <10 minutes, and a detailed contrast sensitivity curve was generated in approximately 30 minutes. CONCLUSIONS: The virtual optomotor system provides a simple and precise method for rapidly quantifying mouse vision. Behavioral measures of vision in mice are essential for interpreting the results of experiments designed to reveal the cellular and molecular mechanisms of vision and visual development and for evaluating potential treatments for visual diseases.

Animals↗

PubMed2003

Developmental plasticity of mouse visual acuity.

Monocular deprivation in mice between postnatal days 19 and 32 has been reported to significantly shift ocular dominance within the binocular region of primary visual cortex; however, it is not known whether visual deprivation in mice during this physiologically defined critical period also results in amblyopia, as it does in other mammals. We addressed this uncertainty by psychophysically assessing in adulthood (postnatal day 70 or older) the grating acuity of normal and monocularly deprived mice, using the Visual Water Task. The visual acuity of mice tested with their nondeprived eyes was equivalent to that of normal mice ( approximately 0.5 cycles/degree); however, acuity measured with eyes monocularly deprived of vision transiently between postnatal days 19 and 32 was reduced by over 30% ( approximately 0.31 cycles/degree). Identical binocular deprivation produced a significant, but smaller, decrease in acuity ( approximately 0.38 cycles/degree). The effects of monocular and binocular deprivation were long lasting and occurred only if visual deprivation occurred between postnatal days 19 and 32. These data indicate that the deleterious effects of early visual deprivation on visual acuity in mice are similar to those reported in other mammals, and together with electrophysiological evidence of ocular dominance plasticity, suggest that the mechanisms of mouse visual plasticity are fundamentally the same as that in other mammals. Therefore, the mouse is probably a good model for investigating the basic cellular and molecular mechanisms underlying visual developmental plasticity and amblyopia.

Age Factors↗

PubMed2002

Variation in visual acuity within pigmented, and between pigmented and albino rat strains.

Many researchers assume that laboratory rats have poor vision, and accordingly, that they need not consider differences in the visual function of rats as a consequence of strain or experience. Currently, it is not specifically known whether rat domestication has negatively affected the visual function of laboratory rat strains, what the effects of strain albinism are on rat visual function, or whether there are strain differences in the visual function of laboratory rats that are independent of pigmentation. In order to address these questions, we measured psychophysically the vertical grating acuity of three pigmented (Dark Agouti, Fisher-Norway, Long-Evans) and three albino (Fisher-344, Sprague-Dawley, Wistar) strains of laboratory rats, and compared their acuity with that of wild rats. The grating thresholds of Dark Agouti, Long-Evans and wild strains clustered around 1.0 cycle/degree (c/d) and did not significantly differ from one another. Fisher-Norway rats, however, had a significantly higher threshold of 1.5 c/d. The grating thresholds of Fisher-344, Sprague-Dawley, and Wistar strains, which were clustered around 0.5 c/d, were significantly lower than those of the pigmented strains. These data demonstrate that there is significant strain variability in the visual function of laboratory rats. Domestication of Long-Evans and Dark Agouti strains does not appear to have compromised visual acuity, but in the case of Fisher-Norway rats, selective breeding may have enhanced their acuity. Strain selection associated with albinism, however, appears to have consistently impaired visual acuity. Therefore, a consideration of strain differences in visual function should accompany the selection of a rat model for behavioral tasks that involve vision, or when comparing visuo-behavioral measurements across rat strains.

Albinism↗