Representing properties locally.

Theories of knowledge such as feature lists, semantic networks, and localist neural nets typically use a single global symbol to represent a property that occurs in multiple concepts. Thus, a global symbol represents mane across HORSE, PONY, and LION. Alternatively, perceptual theories of knowledge, as well as distributed representational systems, assume that properties take different local forms in different concepts. Thus, different local forms of mane exist for HORSE, PONY, and LION, each capturing the specific form that mane takes in its respective concept. Three experiments used the property verification task to assess whether properties are represented globally or locally (e.g., Does a PONY have mane?). If a single global form represents a property, then verifying it in any concept should increase its accessibility and speed its verification later in any other concept. Verifying mane for PONY should benefit as much from having verified mane for LION earlier as from verifying mane for HORSE. If properties are represented locally, however, verifying a property should only benefit from verifying a similar form earlier. Verifying mane for PONY should only benefit from verifying mane for HORSE, not from verifying mane for LION. Findings from three experiments strongly supported local property representation and ruled out the interpretation that object similarity was responsible (e.g., the greater overall similarity between HORSE and PONY than between LION and PONY). The findings further suggest that property representation and verification are complicated phenomena, grounded in sensory-motor simulations.

Circadian-dependent retinal light damage in rats.

PURPOSE: To determine the relative susceptibility of rats to retinal light damage at different times of the day or night. METHODS: Rats maintained in a dim cyclic light or dark environment were exposed to a single dose of intense green light beginning at various times. Normally, light exposures were for 8 or 3 hours, respectively, although longer and shorter periods were also used. Some animals were treated with the synthetic antioxidant dimethylthiourea (DMTU) before or after the onset of light. The extent of visual cell loss was estimated from measurements of rhodopsin and retinal DNA levels 2 weeks after light treatment. The time course of retinal DNA fragmentation, and the expression profiles of heme oxygenase-1 (HO-1) and interphotoreceptor retinol binding protein (IRBP) were determined 1 to 2 days after exposure. RESULTS: When dark-adapted, cyclic light-reared or dark-reared rats were exposed to intense light during normal nighttime hours (2000-0800) the loss of rhodopsin or photoreceptor cell DNA was approximately twofold greater than that found in rats exposed to light during the day (0800-2000). The relative degree of light damage susceptibility persisted in cyclic light-reared rats after dark adaptation for up to 3 additional days. For rats reared in a reversed light cycle, the light-induced loss of rhodopsin was also reversed. Longer duration light treatments revealed that dim cyclic light-reared rats were three- to fourfold more susceptible to light damage at 0100 than at 1700 and that dark-reared animals were approximately twofold more susceptible. Intense light exposure at 0100 resulted in greater retinal DNA fragmentation and the earlier appearance of apoptotic DNA ladders than at 1700. The extent of retinal DNA damage also correlated with an induction of retinal HO-1 mRNA and with a reduction in IRBP transcription. Antioxidant treatment with DMTU was effective in preventing retinal light damage when given before but not after the onset of light. CONCLUSIONS: These results confirm earlier work showing greater retinal light damage in rats exposed at night rather than during the day and extend those findings by demonstrating that a single, relatively short, intense light exposure causes a circadian-dependent, oxidatively induced loss of photoreceptor cells. The light-induced loss of photoreceptor cells is preceded by DNA fragmentation and by alterations in the normal transcriptional events in the retina and within the photoreceptors. The expression profile of an intrinsic retinal factor(s) at the onset of light exposure appears to be important in determining light damage susceptibility.

Light-induced damage in the retina: differential effects of dimethylthiourea on photoreceptor survival, apoptosis and DNA oxidation.

In the rat, photoreceptor cell death from exposure to intense visible light can be prevented by prior treatment with antioxidants. In this study we subjected albino rats raised in dim cyclic light and rats made more susceptible to light damage by rearing in darkness to exposures of green light that led to similar losses of photoreceptor cells. Rhodopsin and photoreceptor DNA, indicators of the number of surviving photoreceptor cells, were determined at various times over a period of 14 days after light exposure. Fragmentation of DNA was determined over a similar time course by neutral and alkaline agarose gel electrophoresis. Apoptosis in retinal DNA was measured by quantitating the appearance of 180 base pair (bp) nucleosomal fragments. Oxidation of DNA was measured by electrochemical detection of the nucleoside 8-hydroxydeoxyguanosine (8-OHdG) after separation by high-performance chromatography. For albino rats reared in dim cyclic light, 24 h of intense light exposure resulted in the loss of 50% rhodopsin and photoreceptor cell DNA. In dark-reared rats, the losses were 40%, respectively, after only 3 h of intense light treatment. In both cases pretreatment with the antioxidant dimethylthiourea (DMTU) prevented rhodopsin and photoreceptor cell DNA loss. The kinetics of the light-induced apoptosis depended markedly on the rearing environment of the rats. The DNA ladders appeared within 12 h of the onset of intense light in the rats reared in dim cyclic light. In these rats the 180 bp fragment was at two-thirds of its maximum intensity immediately after 24 h of light exposure and reached the maximum 12 h later. Dimethylthiourea partially inhibited ladder formation in rats reared in dim cyclic light and delayed the time of appearance of the 180 bp maximum by 6 h. By contrast, in rats reared in darkness the 180 bp fragment was undetected immediately after 3 h of light exposure and reached its maximum 2 days later. Pretreatment with DMTU completely eliminated DNA ladders in these rats. Alkaline gel electrophoresis revealed a pattern of single-strand DNA breaks, with relatively high molecular weight fragments, 6 h after light exposure of dark-reared rats. Single-strand DNA breaks in cyclic light rats corresponded with the onset of apoptotic ladders, but peak values preceded by 12 h the peak of DNA ladder formation. The quantity of 8-OHdG in retinal DNA remained close to control values in all samples with the exception of a peak of twice the control value 18 h after light exposure in the dark-reared rats and a value 60% higher 16 days after exposure in cyclic light animals. Dimethylthiourea had no effect on the amount of oxidized purine in any of the samples. The differences between dark-reared rats and rats reared in dim cyclic light in the kinetics of DNA fragmentation and in their response to treatment with DMTU is consistent with previous observations of fundamental differences in retinal cell physiology in these animals. In dim light-reared rats, the pathway to apoptosis may be qualitatively different from the pathway to net photoreceptor loss in rats reared in darkness. The lack of effect of DMTU on 8-OHdG formation suggests that the oxidation of DNA bases is not a causal factor in light-mediated photoreceptor cell death.

Perceptual symbol systems.

Prior to the twentieth century, theories of knowledge were inherently perceptual. Since then, developments in logic, statistics, and programming languages have inspired amodal theories that rest on principles fundamentally different from those underlying perception. In addition, perceptual approaches have become widely viewed as untenable because they are assumed to implement recording systems, not conceptual systems. A perceptual theory of knowledge is developed here in the context of current cognitive science and neuroscience. During perceptual experience, association areas in the brain capture bottom-up patterns of activation in sensory-motor areas. Later, in a top-down manner, association areas partially reactivate sensory-motor areas to implement perceptual symbols. The storage and reactivation of perceptual symbols operates at the level of perceptual components--not at the level of holistic perceptual experiences. Through the use of selective attention, schematic representations of perceptual components are extracted from experience and stored in memory (e.g., individual memories of green, purr, hot). As memories of the same component become organized around a common frame, they implement a simulator that produces limitless simulations of the component (e.g., simulations of purr). Not only do such simulators develop for aspects of sensory experience, they also develop for aspects of proprioception (e.g., lift, run) and introspection (e.g., compare, memory, happy, hungry). Once established, these simulators implement a basic conceptual system that represents types, supports categorization, and produces categorical inferences. These simulators further support productivity, propositions, and abstract concepts, thereby implementing a fully functional conceptual system. Productivity results from integrating simulators combinatorially and recursively to produce complex simulations. Propositions result from binding simulators to perceived individuals to represent type-token relations. Abstract concepts are grounded in complex simulations of combined physical and introspective events. Thus, a perceptual theory of knowledge can implement a fully functional conceptual system while avoiding problems associated with amodal symbol systems. Implications for cognition, neuroscience, evolution, development, and artificial intelligence are explored.

Basing categorization on individuals and events.

Exemplar, prototype, and connectionist models typically assume that events constitute the basic unit of learning and representation in categorization. In these models, each learning events updates a statistical representation of a category independently of other learning events. An implication is that events involving the same individual affect learning independently and are not integrated into a single structure that represents the individual in an internal model of the world. A series of experiments demonstrates that human subjects track individuals across events, establish representations of them, and use these representations in categorization. These findings are consistent with "representationalism," the view that an internal model of the world constitutes a physical level of representation in the brain, and that the brain does not simply capture the statistical properties of events in an undifferentiated dynamical system. Although categorization is an inherently statistical process that produces generalization, pattern completion, frequency effects, and adaptive learning, it is also an inherently representational process that establishes an internal model of the world. As a result, representational structures evolve in memory to track the histories of individuals, accumulate information about them, and simulate them in events.

Light history and age-related changes in retinal light damage.

PURPOSE: To determine the effects of age and long-term light- or dark-rearing environments on acute, intense-light-mediated retinal degeneration. METHODS: Male albino rats were maintained in a dim cyclic light environment or in darkness for as long as 1 year. When aged 2, 4, 8, and 12 months, some rats were given the synthetic antioxidant dimethylthiourea (DMTU) by intraperitoneal injection and were exposed to intense visible light for as long as 24 hours. Uninjected control rats were exposed to light at the same time. Other rats were treated with light of lower intensity for various periods. Two weeks after intense-light treatment, photoreceptor cell degeneration was estimated by determining the level of rhodopsin and by measuring the content of photoreceptor cell DNA. Light-induced changes in retinal DNA were analyzed immediately after exposure by neutral gel electrophoresis and by 8-hydroxy-deoxyguanosine measurements. Expression of the antioxidative stress protein heme oxygenase-1 (HO-1) was determined by northern blot analysis of mRNA in retinal extracts. RESULTS: At all ages, rats reared in cyclic dim-light conditions had lower rhodopsin levels than did rats reared in darkness; photoreceptor cell DNA levels were unaffected by the rearing environment. Senescent losses in rhodopsin and retinal DNA were significant after rats were 12 months old. Dim-light-reared rats exhibited an age-related increase in retinal light damage susceptibility, whereas dark-reared rats were equally susceptible to damage at all ages. In both types of rats, the mechanism of light-induced cell death involved an apoptotic process, visualized by the pattern of DNA fragments on electrophoretic gels. The process also induced the expression of HO-1 mRNA. Photoreceptor cell loss determined by biochemical measurement, DNA fragmentation, and HO-1 induction were dramatically reduced by the administration of DMTU. CONCLUSIONS: The age-related increase in susceptibility to retinal light damage in rats is influenced by their long-term daily light history. Decreasing retinal irradiance by dark-rearing eliminates the age-related increase in light damage, suggesting a correlation between light environment and retinal gene expression associated with damage. In all rats, retinal light damage resulted in a pattern of DNA fragmentation consistent with apoptotic cell death and in an increased expression of HO-1 mRNA. Antioxidant treatment greatly reduced apoptosis and HO-1 expression. This indicates that light damage involves an oxidative process that may also trigger apoptosis in the retina. The rat aging model may provide useful insights into the role of light environment associated with retinal degeneration in an aging human population.

Reuniting perception and conception.

Work in philosophy and psychology has argued for a dissociation between perceptually-based similarity and higher-level rules in conceptual thought. Although such a dissociation may be justified at times, our goal is to illustrate ways in which conceptual processing is grounded in perception, both for perceptual similarity and abstract rules. We discuss the advantages, power and influences of perceptually-based representations. First, many of the properties associated with amodal symbol systems can be achieved with perceptually-based systems as well (e.g. productivity). Second, relatively raw perceptual representations are powerful because they can implicitly represent properties in an analog fashion. Third, perception naturally provides impressions of overall similarity, exactly the type of similarity useful for establishing many common categories. Fourth, perceptual similarity is not static but becomes tuned over time to conceptual demands. Fifth, the original motivation or basis for sophisticated cognition is often less sophisticated perceptual similarity. Sixth, perceptual simulation occurs even in conceptual tasks that have no explicit perceptual demands. Parallels between perceptual and conceptual processes suggest that many mechanisms typically associated with abstract thought are also present in perception, and that perceptual processes provide useful mechanisms that may be co-opted by abstract thought.

Multiple organisations of events in memory.

Theories of memory organisation propose that activity knowledge organises autobiographical memory globally. According to these views, memories that share a participant, location, or time are only organised together if they also share an activity. If they do not, they are nested within their respective activity organisations locally rather than being organised together globally. Two experiments that assessed people's clustering of laboratory events consistently obtained findings that contradict this view. Both experiments found that people organise event memories globally in non-activity clusters, cross-classify events into multiple organisations, and pivot between activity and non-activity clusters. Consistent with studies of naturalistic events, these studies of laboratory events indicate that people cross-classify event memories simultaneously into multiple global organisations.

The instantiation principle in natural categories.

According to the instantiation principle, the representation of a category includes detailed information about its diverse range of instances. Many accounts of categorisation, including classical and standard prototype theories, do not follow the instantiation principle, because they assume that detailed, exemplar-level information is filtered out of category representations. Nevertheless, the instantiation principle can be implemented in a wide class of models, including both exemplar and abstraction models. To assess the instantiation principle empirically, a parameter-free exemplar-based model of instantiation was applied to typicality judgments for 16 simple categories (e.g. mammal, beverage) and 14 complex categories (e.g. dangerous mammal) in four superordinates (animal, food, small animal, dangerous animal). Across three studies, the model did an excellent job of predicting mean typicality judgments (correlations generally above 0.9) and a good job of predicting standard deviations (fits generally from 0.6 to 0.9). In Study 3, predicting the skew of typicality distributions was successful as well (a fit of 0.87), and dropping atypical exemplars from the simulations degraded prediction. All of these results support the instantiation principle, indicating that subjects incorporate detailed information about category instances into their representations of categories.

DNA repair in the genomic region containing the beta-actin gene in xeroderma pigmentosum complementation group C and normal human cells.

The limited DNA excision repair in UV-irradiated fibroblasts from xeroderma pigmentosum complementation group C (XP-C) occurs in selected chromatin regions. The small beta-actin gene (3.5 kb) is one of these and is repaired as part of a large region (about 50 kb). We show here that only one of the DNA strands is repaired through this extended region. Several genomic fragments spanning about 70 kb in the beta-actin region have been cloned and mapped and some have been examined for repair activity. Both strands of one fragment (14 kb) in the immediate vicinity of the gene are repaired. Transcripts associated with both strands are detected. In normal cells, both strands of the same fragment are preferentially repaired relative to the genome overall and also associated with transcription. The repair activity in XP-C cells associated with other defined DNA fragments indicates that termini for the repaired regions in either strand can be located. Results are consistent with those of others indicating that transcription promotes repair in XP-C cells and that several levels of repair activity, at least one coupled to transcription, occur in normal cells. We conclude that the beta-actin repair domain, defined in XP-C cells, comprises both strands of a small region (about 14 kb) in the vicinity of the beta-actin gene and a single strand extending through a larger region of about 50 kb. We suggest that a similar genomic organization for repair exists in normal cells.

Selective repair of specific chromatin domains in UV-irradiated cells from xeroderma pigmentosum complementation group C.

The limited DNA-excision repair in UV-irradiated nondividing fibroblasts from xeroderma pigmentosum complementation group C (XP-C) occurs in localized chromatin regions generating large DNA segments (at least 30-70 kb) free of pyrimidine dimers. A genomic fraction enriched for this DNA was isolated on the basis of the larger size of the repaired fragments after UV-endonuclease treatment and screened for specific genes. It contains more copies per microgram DNA of two transcriptionally active genes, beta-actin and dihydrofolate reductase, compared to the remaining DNA but an equal number of copies per microgram DNA of an inactive locus termed 754. We confirmed that the active genes were preferentially repaired by measuring the removal of pyrimidine dimers from specific genomic restriction fragments comprising these sequences. These results mean that a unique set of relatively large chromatin domains are repaired in nondividing XP-C cells, even though most of the DNA remains unrepaired. The repaired domains may be those containing the active genes. This specific repair may account for the relatively high UV-resistance of the nondividing cells. In normal cells, a very rapid repair of a restriction fragment containing the beta-actin gene and slow repair of the 754-containing fragment was detected indicating that a similar domain-oriented repair process also exists in these cells. These results are consistent with the previously discovered rapid repair of active genes compared to bulk DNA. Separate damage-recognition systems may exist in human cells for chromatin domains that contain transcribed regions and those that contain no transcribed regions. The latter system may be deficient in XP-C.

Ideals, central tendency, and frequency of instantiation as determinants of graded structure in categories.

Three possible determinants of graded structure (typicality) were observed in common taxonomic categories and goal-derived categories: (1) an exemplar's similarity to ideals associated with goals its category serves; (2) an exemplar's similarity to the central tendency of its category (family resemblance); and (3) an exemplar's frequency of instantiation (people's subjective estimates of how often it is encountered as a category member). Experiment 1 found that central tendency did not predict graded structure in goal-derived categories, although it did predict graded structure in common taxonomic categories. Ideals and frequency of instantiation predicted graded structure in both category types to sizeable and equal extents. A fourth possible determinant--familiarity--did not predict typicality in either common taxonomic or goal-derived categories. Experiment 2 demonstrated that both central tendency and ideals causally determine graded structure, and work showing that frequency causally determines graded structure is discussed. Experiment 2 also demonstrated that the determinants of a particular category's graded structure can change with context. Whereas ideals may determine a category's graded structure in one context, central tendency may determine a different graded structure in another. It is proposed that graded structures do not reflect invariant structures associated with categories but instead reflect people's dynamic ability to construct concepts.