Orwik

General Learning Ability Regulates Exploration Through its Influence on Rate of Habituation

“General intelligence” is purported to influence diverse domain-specific learning abilities in humans, and previous research indicates that an analogous trait is expressed in CD-1 outbred mice. In humans and mice, exploratory tendencies are predictiv... expand abstracte of general cognitive abilities, such that higher cognitive abilities are associated with elevated levels of exploration. However, in mice, repeated exposure to novel environments outside the home cage has been found to up-regulate exploratory tendencies but has no commensurate effect on general learning abilities, suggesting that exploratory tendencies do not causally influence general cognitive performance. This leaves open the question of what is responsible for the robust relationship observed between exploration and general learning abilities? In the present experiments, we find that differential rates of habituation (e.g., to a novel open field) between animals of high and low general learning abilities accounts for the relationship between exploration and learning abilities. First, we up-regulated exploration by exposing mice to a series of novel environments. Similar to its lack of effect on learning tasks, this up-regulation of exploration had no commensurate effect on habituation to novel objects or stimuli. Next we examined the relationship between general learning abilities and exploration under conditions where habituation had a high or low impact on exploratory behaviors. A strong correlation between general learning abilities and exploration was observed under conditions where the levels of habituation (to a novel object or an open field) between animals of high and low general learning abilities were allowed to vary. However, this same correlation was attenuated when the level of habituation attained by animals of high and low general learning abilities was asymptotic or held constant across animals. In total, these results indicate that the relationship between exploration and general learning abilities is accounted for by the impact of habituation (itself a form of learning) on behaviors indicative of exploration. collapse abstract

Longitudinal attentional engagement rescues mice from age-related cognitive declines and cognitive inflexibility.

Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective at... expand abstracttention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm maze task that required the mice to remember and operate on two sets of overlapping guidance (spatial) cues. As previously reported, this training resulted in an immediate (at 4 mo of age) improvement in the animals' aggregate performance across a battery of five learning tasks. Subsequently, these animals received an additional 3 d of working memory training at 3-wk intervals for 15 mo (totaling 66 training sessions), and at 18 mo of age were assessed on a selective attention task, a second set of learning tasks, and variations of those tasks that required the animals to modify the previously learned response. Both attentional and learning abilities (on passive avoidance, active avoidance, and reinforced alternation tasks) were impaired in aged animals that had not received working memory training. Likewise, these aged animals exhibited consistent deficits when required to modify a previously instantiated learned response (in reinforced alternation, active avoidance, and spatial water maze). In contrast, these attentional, learning, and perseverative deficits were attenuated in aged animals that had undergone lifelong working memory exercise. These results suggest that general impairments of learning, attention, and cognitive flexibility may be mitigated by a cognitive exercise regimen that requires chronic attentional engagement. collapse abstract

Individual Differences in Animal Intelligence: Learning, Reasoning, Selective Attention and Inter-Species Conservation of a Cognitive Trait

Humans’ performance on most cognitive tasks are commonly regulated by an underlying latent variable (i.e., “general” intelligence), and the expression of this latent modulator of cognitive performance varies across individuals. While “intelligence” i... expand abstractn humans is easily recognized, a precise definition of this trait has proven elusive, and has impeded efforts to compare the emergence of this trait across species. Here we describe our efforts to characterize this cognitive trait in genetically heterogeneous laboratory mice. Using batteries of as many as eight learning tasks and various principal component analysis regimens, we have found a robust general factor that accounts for nearly 40% of the variance of individual animals across all tasks. This “general learning factor” is not attributable to variations in stress reactivity or exploratory tendencies. However, like human intelligence, this general factor covaries with the efficacy of selective attention and working memory capacity. Importantly, we also find that general learning abilities covary with animals’ performance on novel tests of reasoning. In total, this work indicates that learning abilities, attentional control, and the capacity for reasoning, features that constitute both colloquial and formal definitions of human intelligence, are commonly regulated in individual genetically heterogeneous mice. These results suggest an evolutionary conservation of the qualitative and quantitative properties of intelligence, and indicate that like humans, sub-human animals express individual differences in this trait. collapse abstract

A dopaminergic gene cluster in the prefrontal cortex predicts performance indicative of general intelligence in genetically heterogeneous mice.

Genetically heterogeneous mice express a trait that is qualitatively and psychometrically analogous to general intelligence in humans, and as in humans, this trait co-varies with the processing efficacy of working memory (including its dependence on ... expand abstractselective attention). Dopamine signaling in the prefrontal cortex (PFC) has been established to play a critical role in animals' performance in both working memory and selective attention tasks. Owing to this role of the PFC in the regulation of working memory, here we compared PFC gene expression profiles of 60 genetically diverse CD-1 mice that exhibited a wide range of general learning abilities (i.e., aggregate performance across five diverse learning tasks). collapse abstract

Working Memory Training Promotes General Cognitive Abilities in Genetically Heterogeneous Mice

In both humans and mice, the efficacy of working memory capacity and its related process, selective attention, are each strongly predictive of individuals' aggregate performance in cognitive test batteries [ [1], [2], [3], [4], [5], [6], [7], [8] and... expand abstract [9]]. Because working memory is taxed during most cognitive tasks, the efficacy of working memory may have a causal influence on individuals' performance on tests of “intelligence” [ [10] and [11]]. Despite the attention this has received, supporting evidence has been largely correlational in nature (but see [12]). Here, genetically heterogeneous mice were assessed on a battery of five learning tasks. Animals' aggregate performance across the tasks was used to estimate their general cognitive abilities, a trait that is in some respects analogous to intelligence [ [13] and [14]]. Working memory training promoted an increase in animals' selective attention and their aggregate performance on these tasks. This enhancement of general cognitive performance by working memory training was attenuated if its selective attention demands were reduced. These results provide evidence that the efficacy of working memory capacity and selective attention may be causally related to an animal's general cognitive performance and provide a framework for behavioral strategies to promote those abilities. Furthermore, the pattern of behavior reported here reflects a conservation of the processes that regulate general cognitive performance in humans and infrahuman animals. collapse abstract

Selective Attention, Working Memory, and Animal Intelligence

Accumulating evidence indicates that the storage and processing capabilities of the human working memory system co-vary with individuals’ performance on a wide range of cognitive tasks. The ubiquitous nature of this relationship suggests that variati... expand abstractons in these processes may underlie individual differences in intelligence. Here we briefly review relevant data which supports this view. Furthermore, we emphasize an emerging literature describing a trait in genetically heterogeneous mice that is quantitatively and qualitatively analogous to general intelligence (g) in humans. As in humans, this animal analog of g co-varies with individual differences in both storage and processing components of the working memory system. Absent some of the complications associated with work with human subjects (e.g., phonological processing), this work with laboratory animals has provided an opportunity to assess otherwise intractable hypotheses. For instance, it has been possible in animals to manipulate individual aspects of the working memory system (e.g., selective attention), and to observe causal relationships between these variables and the expression of general cognitive abilities. This work with laboratory animals has coincided with human imaging studies (briefly reviewed here) which suggest that common brain structures (e.g., prefrontal cortex) mediate the efficacy of selective attention and the performance of individuals on intelligence test batteries. In total, this evidence suggests an evolutionary conservation of the processes that co-vary with and/or regulate “intelligence” and provides a framework for promoting these abilities in both young and old animals. collapse abstract

Deletion of PEA-15 in mice is associated with specific impairments of spatial learning abilities.

BACKGROUND: PEA-15 is a phosphoprotein that binds and regulates ERK MAP kinase and RSK2 and is highly expressed throughout the brain. PEA-15 alters c-Fos and CREB-mediated transcription as a result of these interactions. To determine if PEA-15 contri... expand abstractbutes to the function of the nervous system we tested mice lacking PEA-15 in a series of experiments designed to measure learning, sensory/motor function, and stress reactivity. RESULTS: We report that PEA-15 null mice exhibited impaired learning in three distinct spatial tasks, while they exhibited normal fear conditioning, passive avoidance, egocentric navigation, and odor discrimination. PEA-15 null mice also had deficient forepaw strength and in limited instances, heightened stress reactivity and/or anxiety. However, these non-cognitive variables did not appear to account for the observed spatial learning impairments. The null mice maintained normal weight, pain sensitivity, and coordination when compared to wild type controls. CONCLUSION: We found that PEA-15 null mice have spatial learning disabilities that are similar to those of mice where ERK or RSK2 function is impaired. We suggest PEA-15 may be an essential regulator of ERK-dependent spatial learning. collapse abstract

Parsing storage from retrieval in experimentally induced amnesia.

Age-related impairments of new memories reflect failures of learning, not retention.

Learning impairments and the instability of memory are defining characteristics of cognitive aging. However, it is unclear if deficits in the expression of new memories reflect an accelerated decay of the target memory or a consequence of inefficient... expand abstract learning. Here, aged mice (19-21-mo old) exhibited acquisition deficits (relative to 3-5-mo old mice) on three learning tasks, although these deficits were overcome with additional training. When tested after a 30-d retention interval, the performance of aged animals was impaired if initial learning had been incomplete. However, if trained to equivalent levels of competence, aged animals exhibited no retention deficits relative to their young counterparts. These results suggest that age-related "memory" impairments can be overcome through a more effective learning regimen. collapse abstract

Selective attention, working memory, and animal intelligence.

Accumulating evidence indicates that the storage and processing capabilities of the human working memory system co-vary with individuals' performance on a wide range of cognitive tasks. The ubiquitous nature of this relationship suggests that variati... expand abstractons in these processes may underlie individual differences in intelligence. Here we briefly review relevant data which supports this view. Furthermore, we emphasize an emerging literature describing a trait in genetically heterogeneous mice that is quantitatively and qualitatively analogous to general intelligence (g) in humans. As in humans, this animal analog of g co-varies with individual differences in both storage and processing components of the working memory system. Absent some of the complications associated with work with human subjects (e.g., phonological processing), this work with laboratory animals has provided an opportunity to assess otherwise intractable hypotheses. For instance, it has been possible in animals to manipulate individual aspects of the working memory system (e.g., selective attention), and to observe causal relationships between these variables and the expression of general cognitive abilities. This work with laboratory animals has coincided with human imaging studies (briefly reviewed here) which suggest that common brain structures (e.g., prefrontal cortex) mediate the efficacy of selective attention and the performance of individuals on intelligence test batteries. In total, this evidence suggests an evolutionary conservation of the processes that co-vary with and/or regulate "intelligence" and provides a framework for promoting these abilities in both young and old animals. collapse abstract

Higher-order associative processing in hermissenda suggests multiple sites of neuronal modulation

Higher-order associative processing in Hermissenda suggests

AmnesiaReview Retrieval failure versus memory loss in experimental amnesia: Definitions and processes

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Impaired working memory duration but normal learning abilities found in mice that are conditionally deficient in the close homolog of L1.

In addition to its role in axon growth and neuronal migration, the close homolog of L1 (CHL1), a member of the L1 family of cell adhesion molecules, is involved in synaptic plasticity. To date, little has been done to disassociate the role of CHL1 du... expand abstractring adulthood from its role during development. To address this issue, mice conditionally deficient in CHL1 (lacking CHL1 only after the third postnatal week) were tested relative to littermate controls as adults in five learning tasks and several tests of working memory (including duration and selective attention). CHL1-deficient mice showed no impairments in the learning tasks compared with wild-type controls. CHL1 deletion had no effect on selective attention despite its widespread impairment of working memory duration. These results suggest a role for CHL1 in the adult-brain in the short-term maintenance of information. collapse abstract

Domain-specific and domain-general learning factors are expressed in genetically heterogeneous CD-1 mice

It has been established that both domain-specific (e.g. spatial) as well as domain-general (general intelligence) factors influence human cognition. However, the separation of these processes has rarely been attempted in studies using laboratory anim... expand abstractals. Previously, we have found that the performances of outbred mice across a wide range of learning tasks correlate in such a way that a single factor can explain 30–44% of the variance between animals. This general learning factor is in some ways qualitatively and quantitatively analogous to general intelligence in humans. The complete structure of cognition in mice, however, has not been explored due to the limited sample sizes of our previous analyses. Here we report a combined analysis from 241 CD-1 mice tested in five primary learning tasks, and a subset of mice tested in two additional learning tasks. At least two (possibly three) of the seven learning tasks placed explicit demands on spatial and/or hippocampus-dependent processing abilities. Consistent with previous findings, we report a robust general factor influencing learning in mice that accounted for 38% of the variance across tasks. In addition, a domain-specific factor was found to account for performance on that subset of tasks that shared a dependence on hippocampal and/or spatial processing. These results provide further evidence for a general learning/cognitive factor in genetically heterogeneous mice. Furthermore (and similar to human cognitive performance), these results suggest a hierarchical structure to cognitive processes in this genetically heterogeneous species. collapse abstract

Age-related declines in general cognitive abilities of BalbC mice are associated with disparities in working memory, body weight, and general activity.

A defining characteristic of age-related cognitive decline is a deficit in general cognitive performance. Here we use a testing and analysis regimen that allows us to characterize the general learning abilities of young (3-5 mo old) and aged (19-21 m... expand abstracto old) male and female Balb/C mice. Animals' performance was assessed on a battery of seven diverse learning tasks. Aged animals exhibited deficits in five of the seven tasks and ranked significantly lower than their young counterparts in general learning abilities (aggregate performance across the battery of tasks). Aging added variability to common core performance (i.e., general learning ability), which translated into increased variability on the individual cognitive tasks. Relatedly, general learning abilities did not differ between the two ages among the best quartile of learners (i.e., cognitive abilities were spared in a subsample of the aged animals). Additionally, working memory capacity (resistance to interference) and duration (resistance to decay) accounted for significantly more of the variability in general learning abilities in aged relative to young animals. Tests of 15 noncognitive performance variables indicated that an increase in body weight (and an associated decrease in general activity) was characteristic of those aged animals which exhibited deficient general learning abilities. These results suggest the possibility that general cognitive deficits in aged animals reflect a failure of specific components of the working memory system, and may be related to variations in body weight and an associated decrease in activity. collapse abstract

Up-regulation of exploratory tendencies does not enhance general learning abilities in juvenile or young-adult outbred mice.

"General cognitive ability" describes a trait that transcends specific learning domains and impacts a wide range of cognitive skills. Individual animals (including humans) exhibit wide variations in their expression of this trait. We have previously ... expand abstractdetermined that the propensity for exploration is highly correlated with the general cognitive abilities of individual outbred mice. Here, we asked if inducing an increase in exploratory behaviors would causally promote an increase in animals' general learning abilities. In three experiments, juvenile and young-adult male CD-1 outbred mice were exposed to 12 novel environments starting at post-natal days 39 (juvenile) and 61 (young adult), after which they underwent a series of cognitive and exploratory tests as adults (beginning at post-natal day 79). Exposure to novel environments promoted increases in exploration (across multiple measures) on two different tasks, including an elevated plus maze. However, a subsequent test of general learning abilities (aggregate performance across five distinct learning tasks) determined that exposure to novel environments as juveniles or young-adults had no effect on general learning abilities in adulthood. Therefore, while exposure to novel environments promotes long-lasting increases in mice's exploratory tendencies, these increases in exploration do not appear to causally impact general learning abilities. collapse abstract

Information Processing and Age-Related Declines in General Cognitive Abilities

DESCRIPTION (provided by applicant): Animal research on age-related cognitive deficits has typically focused on the impact of aging on specific learning tasks or domains. While informative regarding the brain substrates for task- specific (or even ... expand abstractdomain-specific) learning impairments, this approach provides little insight into the impact of aging on general cognitive/learning abilities. The prevailing focus on isolated tasks or domains has limited our understanding of "cognitive aging", as it has been estimated that 35-60% of age-related declines in cognitive performance are attributable to a diminishment of individuals' general cognitive ability, i.e., the capacity for cognitive performance that transcends the specific demands of any single task or domain. We have developed unique testing and analysis regimens that are sensitive to a general learning factor that accounts for >32% of the variance in the general cognitive performance of young adult laboratory mice. We have begun to apply this approach to studies of animals across the life span, and have isolated a general cognitive factor in 20 month old BALB-C mice that accounts for greater than 40% of the variance in the general cognitive abilities of these animals. While comparable in structure to that of young animals, in old animals this "general cognitive factor" consistently accounts for a greater proportion of the total variance in the cognitive performance of aged animals, suggesting that general cognitive abilities become increasingly dominant across the animal's life span. Moreover, we have established that in aged animals, general cognitive abilities become increasingly reliant on aspects of working memory, particularly, working memory span (resistance to decay) and working memory capacity (resistance to interference). Furthermore, general cognitive declines do not accrue homogeneously across the life span, such that some percentage of aged animals retain their cognitive abilities, while in others, these abilities decline rapidly, an effect associated with increasing body mass and decreases in general activity. We now hypothesize that the general cognitive decline in aged animals is the consequence of perturbations in the efficacy of the working memory system, including working memory span, capacity, and selective attention. We will test these possibilities in Aims 1 and 2, and in so doing, will gain critical insight into the processes that underlie age-related cognitive declines. It will then be possible in Aim 3 to test specific behavioral strategies (including manipulations of body weights, activity, and working memory efficacy) to innoculate animals against these declines, and possibly, to mitigate the progression of age-related declines that were previously instantiated. This work will provide a conceptually and empirically strong foundation for subsequent elucidation of the brain substrates for age-related cognitive impairments (as described in our Ancillary Aim), and ultimately, the development of strategies to overcome these impairments. PUBLIC HEALTH RELEVANCE: A critical need has emerged to develop strategies with which to treat the normal but pervasive cognitive impairments that are associated with aging. To do so, we must quantify the cognitive deficits associated with aging, understand the variability (i.e., individual differences) in the emergence of cognitive aging, and elucidate the psychological processes that underlie cognitive aging. The goal of this research program is to quantify cognitive declines across the life span, and to generate behavioral intervention strategies that facilitate the successful maintenance of cognitive abilities into old age. collapse abstract

Neuronal cell adhesion molecule deletion induces a cognitive and behavioral phenotype reflective of impulsivity.

Cell adhesion molecules, such as neuronal cell adhesion molecule (Nr-CAM), mediate cell-cell interactions in both the developing and mature nervous system. Neuronal cell adhesion molecule is believed to play a critical role in cell adhesion and migra... expand abstracttion, axonal growth, guidance, target recognition and synapse formation. Here, wild-type, heterozygous and Nr-CAM null mice were assessed on a battery of five learning tasks (Lashley maze, odor discrimination, passive avoidance, spatial water maze and fear conditioning) previously developed to characterize the general learning abilities of laboratory mice. Additionally, all animals were tested on 10 measures of sensory/motor function, emotionality and stress reactivity. We report that the Nr-CAM deletion had no impact on four of the learning tasks (fear conditioning, spatial water maze, Lashley maze and odor discrimination). However, Nr-CAM null mice exhibited impaired performance on a task that required animals to suppress movement (passive avoidance). Although Nr-CAM mutants expressed normal levels of general activity and body weights, they did exhibit an increased propensity to enter stressful areas of novel environments (the center of an open field and the lighted side of a dark/light box), exhibited higher sensitivity to pain (hot plate) and were more sensitive to the aversive effects of foot shock (shock-induced freezing). This behavioral phenotype suggests that Nr-CAM does not play a central role in the regulation of general cognitive abilities but may have a critical function in regulating impulsivity and possibly an animal's susceptibility to drug abuse and addiction. collapse abstract

Pharmacological modulation of stress reactivity dissociates general learning ability from the propensity for exploration.

It has previously been reported that general learning ability (GLA) correlates positively with exploratory tendencies in individual outbred mice. This finding suggests the possibility that variations in stress reactivity modulate GLA and thus its rel... expand abstractationship to exploratory tendencies. Here, the authors investigated the potential role of stress reactivity in regulating this relationship by assessing the effects of the anxiolytic chlorodiazepoxide (CDP; 10 mg/kg) on subjects' performance in a battery of diverse learning tasks as well as exploratory behaviors and stress reactivity. CDP-treated mice exhibited reductions in stress-induced corticosterone levels and behavioral reactivity to mild stressors and a corresponding increase in exploration. However, CDP-treated mice did not exhibit facilitated acquisition of any of the learning tasks and expressed GLA comparable to controls. Results indicate that although reduced stress reactivity promotes exploration, this does not translate into an up-regulation of GLA, suggesting that the relationship between GLA and exploration is not mediated by stress reactivity. The authors propose that variations in GLA reflect individuals' propensity for novelty seeking, whereas exploration reflects both stress reactivity and novelty seeking, the latter of which may underlie the relationship between exploration and GLA. collapse abstract

Selective Attention is a Primary Determinant of the Relationship between Working Memory and General Learning Ability in Outbred Mice

A single factor (i.e., general intelligence) can account for much of an individuals’ performance across a wide variety of cognitive tests. However, despite this factor’s robustness, the underlying process is still a matter of debate. To address this ... expand abstractquestion, we developed a novel battery of learning tasks to assess the general learning abilities (GLAs) of mice. Using this battery, we previously reported a strong relationship between GLA and a task designed to tax working memory capacity (i.e., resistance to competing demands). Here we further explored this relationship by investigating which aspects of working memory (storage or processing) best predict GLAs in mice. We found that a component of working memory, selective attention, correlated with GLA comparably to working memory capacity. However, this relationship was not found for two other components of working memory, short-term memory capacity and duration. These results provide further evidence that variations in aspects of working memory and executive functions covary with general cognitive abilities. collapse abstract

Retrieval failure versus memory loss in experimental amnesia: definitions and processes.

For at least 40 years, there has been a recurring argument concerning the nature of experimental amnesia, with one side arguing that amnesic treatments interfere with the formation of enduring memories and the other side arguing that these treatments... expand abstract interfere with the expression of memories that were effectively encoded. The argument appears to stem from a combination of (1) unclear definitions and (2) real differences in the theoretical vantages that underlie the interpretation of relevant data. Here we speak to how the field might avoid arguments that are definitional in nature and how various hypotheses fare in light of published data. Existing but often overlooked data favor very rapid (milliseconds) synaptic consolidation, with experimental amnesia reflecting, at least in part, deficits in retrieval rather than in the initial storage of information. collapse abstract

Exploration in outbred mice covaries with general learning abilities irrespective of stress reactivity, emotionality, and physical attributes.

Across multiple learning tasks (that place different sensory, motor, and information processing demands on the animals), we have found that the performance of mice is commonly regulated by a single factor ("general learning") that accounts for 30-40%... expand abstract of the variance across individuals and tasks. Furthermore, individuals' general learning abilities were highly correlated with their propensity to engage in exploration in an open field, a behavior that is potentially stress-inducing. This relationship between exploration in the open field and general learning abilities suggests the possibility that variations in stress sensitivity/responsivity or related emotional responses might directly influence individuals' general learning abilities. Here, the relationship of sensory/motor skills and stress sensitivity/emotionality to animals' general learning abilities were assessed. Outbred (CD-1) mice were tested in a battery of six learning tasks as well as 21 tests of exploratory behavior, sensory/motor function and fitness, emotionality, and stress reactivity. The performances of individual mice were correlated across six learning tasks, and the performance measures of all learning tasks loaded heavily on a single factor (principal component analysis), accounting for 32% of the variability between animals and tasks. Open field exploration and seven additional exploratory behaviors (including those exhibited in an elevated plus maze) also loaded heavily on this same factor, although general activity, sensory/motor responses, physical characteristics, and direct measures of fear did not. In a separate experiment, serum corticosterone levels of mice were elevated in response to a mild environmental stressor (confinement on an elevated platform). Stress-induced corticosterone levels were correlated with behavioral fear responses, but were unsystematically related to individuals' propensity for exploration. In total, these results suggest that although general learning abilities are strongly related to individuals' propensity for exploration, this relationship is not attributable to variations in sensory/motor function or the individuals' physiological or behavioral sensitivity to conditions that promote stress or fear. collapse abstract

Variations in working memory capacity predict individual differences in general learning abilities among genetically diverse mice.

Up to 50% of an individuals' performance across a wide variety of distinct cognitive tests can be accounted for by a single factor (i.e., "general intelligence"). Despite its ubiquity, the processes or mechanisms regulating this factor are a matter o... expand abstractf considerable debate. Although it has been hypothesized that working memory may impact cognitive performance across various domains, tests have been inconclusive due to the difficulty in isolating working memory from its overlapping operations, such as verbal ability. We address this problem using genetically diverse mice, which exhibit a trait analogous to general intelligence. The general cognitive abilities of CD-1 mice were found to covary with individuals' working memory capacity, but not with variations in long-term retention. These results provide evidence that independent of verbal abilities, variations in working memory are associated with general cognitive abilities, and further, suggest a conservation across species of mechanisms and/or processes that regulate cognitive abilities. collapse abstract

In Memoriam: Charles F. Flaherty, Ph.D.

No abstrct available for this article

General Cognitive Learning Deficits in Aged Mice

Animal research on age-related learning deficits has typically focused on the impact of age on specific learning systems. While informative, this work necessarily limits any conclusions regarding the effects of aging on general cognitive/learning abi... expand abstractlities. This focus on specific learning systems impacts critically on our understanding of age-related deficits, given that it is estimated that 25-50% of this decline is attributable to an impairment of general cognitive ability, i.e., an ability that transcends specific learning systems or domains. The elucidation of the brain substrates for age-related cognitive deficits thus requires a conceptually-sound approach from which to parse deficits in general abilities from those which impact specific (limited) domains. Absent any attention to general influences on learning/cognitive processes, as much as 50% of decline in cognitive abilities that accrue with aging willnecessarily go unexplained, mitigating the development of effective treatment strategies.Among human populations, a general influence on individuals' learning abilities reflects one of the most dominant cognitive traits ever identified. However, comparable evidence from animal subjects is sparse, and age-dependent variations in general learning factors have never been described in laboratory animals. We have recently developed a unique test battery that is sensitive to a general learning factor in mice, and this factor is psychometrically comparable to that described in humans. In Aims 1 and 2 of the present proposal, we summarize our plans to characterize the general learning/cognitive abilities of laboratory mice that range in age from young to old, and describe analysis regimens that will provide preliminary indications of thedifferential sources of variability that impinge on these abilities across the life span. These studies are a critical prelude to future work directed at the elucidation of the brain substrates for age-related declines in general cognitive/learning abilities. collapse abstract