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Landmark discrimination learning in the dog: effects of age, an antioxidant fortified food, and cognitive strategy.

The landmark discrimination learning test can be used to assess the ability to utilize allocentric spatial information to locate targets. The present experiments examined the role of various factors on performance of a landmark discrimination learning task in beagle dogs. Experiments 1 and 2 looked at the effects of age and food composition. Experiments 3 and 4 were aimed at characterizing the cognitive strategies used in performance on this task and in long-term retention. Cognitively equivalent groups of old and young dogs were placed into either a test group maintained on food enriched with a broad-spectrum of antioxidants and mitochondrial cofactors, or a control group maintained on a complete and balanced food formulated for adult dogs. Following a wash-in period, the dogs were tested on a series of problems, in which reward was obtained when the animal responded selectively to the object closest to a thin wooden block, which served as a landmark. In Experiment 1, dogs were first trained to respond to a landmark placed directly on top of coaster, landmark 0 (L0). In the next phase of testing, the landmark was moved at successively greater distances (1, 4 or 10 cm) away from the reward object. Learning varied as a function of age group, food group, and task. The young dogs learned all of the tasks more quickly than the old dogs. The aged dogs on the enriched food learned L0 significantly more rapidly than aged dogs on control food. A higher proportion of dogs on the enriched food learned the task, when the distance was increased to 1cm. Experiment 2 showed that accuracy decreased with increased distance between the reward object and landmark, and this effect was greater in old animals. Experiment 3 showed stability of performance, despite using a novel landmark, and new locations, indicating that dogs learned the landmark concept. Experiment 4 found age impaired long-term retention of the landmark task. These results indicate that allocentric spatial learning is impaired in an age-dependent manner in dogs, and that age also affects performance when the distance between the landmark and target is increased. In addition, these results both support a role of oxidative damage in the development of age-associated cognitive dysfunction and indicate that short-term administration of a food enriched with supplemental antioxidants and mitochondrial cofactors can partially reverse the deleterious effects of aging on cognition.

Age Factors↗

Dopamine D1-like receptors and reward-related incentive learning.

There now is general agreement that dopaminergic neurons projecting from ventral mesencephalic nuclei to forebrain targets play a critical role in reward-related incentive learning. Many recent experiments evaluate the role of dopamine (DA) receptor subtypes in various paradigms involving this type of learning. The first part of this paper reviews evidence from these studies that use antagonists or agonists relatively specific for D1- or D2-like receptors in operant paradigms with food, brain stimulation, self-administered stimulant or conditioned rewards or place conditioning. The focus is on studies that directly compare agents acting at the two DA receptor families, especially those studies where the agents produce differential actions. Results support the conclusion that D1-like receptors play a more critical role in reward-related learning than D2-like receptors. D1-like receptors initiate a cascade of intracellular events including cyclic adenosine monophosphate (cAMP) formation and activation of cAMP-dependent protein kinase (PKA). The final section of this paper reviews evidence from a wide range of neuroscience experiments that implicates the cAMP/PKA pathway in learning in general and in reward-related incentive learning in particular. We conclude that the molecular mechanism underlying DA-mediated incentive learning may involve DA release in association with reward, stimulation of D1-like receptors, activation of the cAMP/PKA cascade and additional intracellular events leading to modification of cortico-striatal glutamatergic synapses activated by stimuli encountered in close temporal contiguity with reward. Thus, when reward-related incentive learning takes place, it may be the action of DA acting at D1-like receptors that leads to plastic changes in the striatum that form the substrate of that learning.

Animals↗

Chronic cerebral hypoperfusion disrupts discriminative behavior in acquired-learning rats.

We describe an 'acquired-learning' rat model that was used to investigate the effects of chronic cerebral hypoperfusion on the maintenance of previously acquired discriminative behavior using the discriminating learning task. Male Wistar rats, aged 11 weeks, were trained to discriminate between lamp-on and lamp-off states under an operant-type learning procedure. After 30 sessions, we selected 'acquired-learning' rats with an average discrimination ratio higher than 75% recorded during the last three sessions. Chronic hypoperfusion was then induced by permanent ligation of both common carotid arteries under pentobarbital anesthesia. The rats were tested after surgery over a period of 12 weeks and brain tissue was analyzed for muscarinic acetylcholine receptor (mACh-R) binding. Cerebral hypoperfusion resulted in a significant reduction in the discrimination ratio throughout the observation period, compared with sham-operated rats. However, chronic hypoperfusion would not affect on motor function. The maximum number of mACh-R examined 12 weeks after the operation was significantly reduced in the frontal cortex and hippocampus in the hypoperfusion group. Impaired discrimination learning was associated with a reduction in mACh-R. Our findings suggest that chronic cerebral hypoperfusion in acquired-learning rats is a useful model for investigating the pathophysiology of dementia and that cortical and/or hippocampal cholinergic systems contributes to learning impairment, at least, in our learning task.

Analysis of Variance↗

Learning and memory impairment in cocaine-dependent and comorbid schizophrenic patients.

Impairments in verbal learning and memory functioning have been found to be cardinal features among individuals with schizophrenia as well as among non-schizophrenic cocaine abusers. Cognitive deficits in these areas, moreover, have been associated with poor treatment response and short-term outcome. Little is known, however, about the acute effects of cocaine abuse on schizophrenic patients' learning and memory functioning. Consequently, a potentially reversible and treatable source of cognitive impairment has been virtually ignored. The present study examined the extent of verbal learning and memory impairment in a group of cocaine-dependent schizophrenic patients (n=42) and a group of non-schizophrenic cocaine-dependent patients (n=21) within 72 h of the last cocaine use using the California Verbal Learning Test (CVLT). Schizophrenic patients (n=34) without any substance-use disorders were also tested in an identical time frame and served as a comparison group. Results revealed that all groups demonstrated significant learning and memory impairment relative to CVLT published age and gender corrected norms. Both cocaine-dependent and non-substance abusing schizophrenic groups presented a very similar pattern of impaired learning and recall performance across all CVLT task domains. Comorbid patients, in contrast, presented with marked deficits in their ability to learn and recall verbal information relative to either schizophrenic or cocaine-only groups. Moreover, the cocaine-abusing schizophrenic patients showed significant forgetfulness of the information that they did acquire during delayed recall conditions. The performance deficits exhibited by cocaine-abusing schizophrenic patients differed not only in relative severity of impairment, but also qualitatively in their increased rates of forgetfulness of acquired information. These results are interpreted in terms of the neurobiological substrates of learning and memory and the neurobiological impact of cocaine on schizophrenic patients' cognition during the early phase of inpatient hospitalization. These results suggest that comorbid patients should be targeted for specialized remediation efforts at the beginning phases of inpatient treatment.

Acute Disease↗

Involvement of mu(1)-opioid receptors and cholinergic neurotransmission in the endomorphins-induced impairment of passive avoidance learning in mice.

The effects of naloxonazine, a mu(1)-opioid receptor antagonist, and physostigmine, a cholinesterase inhibitor, on the endomorphins-induced impairment of passive avoidance learning were investigated in mice. Endomorphin-1 (10 microg) and endomorphin-2 (10 microg) significantly impaired passive avoidance learning, while naloxonazine (35 mg/kg, s.c.), a mu(1)-opioid receptor antagonist, which alone failed to influence passive avoidance learning significantly inhibited the endomorphin-1 (10 microg)- but not endomorphin-2 (10 microg)-induced disturbance of such learning. A rather nonselective higher dose (50 mg/kg, s.c.) of naloxonazine almost completely antagonized the endomorphin-1 (10 microg)- and endomorphin-2 (10 microg)-induced impairment of passive avoidance learning. In contrast, physostigmine (0.025 and 0.05 mg/kg, i.p.) significantly reversed the endomorphin-1 (10 microg)- and endomorphin-2 (10 microg)-induced disturbance of passive avoidance learning, whereas physostigmine (0.025 and 0.05 mg/kg, i.p.) alone did not influence such learning. These results suggest that endomorphin-1 but not endomorphin-2 impairs learning and memory resulting from cholinergic dysfunction, and from activation of mu(1)-opioid receptors.

Animals↗

Human and social capital as facilitators of lifelong learning in nursing.

To ensure that lifelong learning is, and remains, a reality as a vehicle for facilitating continuing professional learning in nursing, certain mechanisms need to be instituted specifically for this purpose. Some of the key organisational facilitators for achieving this include individual performance reviews, Workforce Development Confederations, professional self-regulation, and Investors in People awards. In a study exploring nurses' perceptions of lifelong learning, it emerged that in addition to the organisational mechanisms that are necessary to achieve this aspiration, there are also various non-organisational or informal factors at work that enable nurses to initiate and continue professional learning. It seems that substantial informal teaching, learning and facilitation of learning occur through work-based contacts with other healthcare professionals, and this is complemented by support from non-healthcare related other significant individuals. These factors seem to constitute the notion of human and social capital (HSC), which is a concept that has been implicated as a significant instigator or enabler of professional learning. This paper examines these non-organisational factors, clarifies the meanings and roles of human capital and social capital in healthcare, and discusses their implications for lifelong learning in nursing. The analysis is supported by findings from a qualitative study, which comprised of 27 semi-structured individual interviews and two focus groups with RNs on D grade and above.

Education, Nursing, Continuing↗

Long-term potentiation: a good model for learning and memory?

1. Long-term potentiation (LTP), long-term depression (LTD), and depotentiation of synaptic activity have been suggested to model synaptic plastic changes that occur during learning. Recent reports however show that neither LTP induced by high frequency stimulation (HFS) in the dentate, CA3, or CA1, nor depotentiation in area CA1 of the hippocampus, are reliable models of the learning abilities of rats or mice. LTD cannot reliably be obtained in the hippocampus in vivo and might be an artefact caused by altered inhibitory transmission. 2. Experiments with gene deletion ('knock out') mice strains show that mice that do not express HFS-induced LTP in the dentate are able to learn spatial tasks. 3. Studies of the effect of NMDA receptor blockers also showed that HFS-induced LTP in the dentate is not a model for processes that occur during learning. Studies using drugs that act on metabotropic glutamate receptors showed that HFS-induced LTP or depotentiation of LTP in area CA1 are not models for learning mechanisms either. 4. Neither in vivo recording of naturally-occurring LTP in the dentate nor synaptic saturation experiments in the hippocampus was able to support the theory that LTP occurs during learning. 5. While in vitro experiments are essential tools to investigate cellular and subcellular mechanisms that underlay synaptic transmission, measurements of LTP, LTD, or DP are not reliable models for learning processes and cannot replace experiments with intact animals that learn spatial tasks.

Animals↗

Neural mechanisms of mammalian olfactory learning.

In this review, we compare the neural basis of olfactory learning in three specialized contexts that occur during sensitive periods of enhanced neural plasticity. Although they involve very different behavioural contexts, they share several common features, including a dependence on noradrenergic transmission in the olfactory bulb. The most extensively characterized of these examples is the learning of pheromonal information by female mice during mating. While this form of learning is unusual in that the neural changes underlying the memory occur in the accessory olfactory bulb at the first stage of sensory processing, it involves similar neural mechanisms to other forms of learning and synaptic plasticity. The learning of newborn lamb odours after parturition in sheep, and the olfactory conditioning in neonatal animals such as rats and rabbits, are mediated by the main olfactory system. Although the neural mechanisms for learning in the main olfactory system are more distributed, they also involve changes occurring in the olfactory bulb. In each case, odour learning induces substantial structural and functional changes, including increases in inhibitory neurotransmission. In the main olfactory bulb, this probably represents a sharpening of the odour-induced pattern of activity, due to increases in lateral inhibition. In contrast, the different morphology of mitral cells in the accessory olfactory bulb results in increased self-inhibition, disrupting the transmission of pheromonal information. Although these examples occur in highly specialized contexts, comparisons among them can enhance our understanding of the general neural mechanisms of olfactory learning.

Animals↗

Effects of GABAergic drugs on physostigmine-induced improvement in memory acquisition of passive avoidance learning in mice.

1. The effect of gamma-aminobutyric acid (GABA) receptor agonists and antagonists on acquisition of a step-down passive avoidance learning in mice was measured in the presence and absence of physostigmine. 2. Intraperitoneal injection of different doses of the anticholinesterase drug physostigmine (0.1-0.3 mg/kg) increased acquisition in mice dose dependently. The maximum response was obtained with 0.3 mg/kg of the drug. Higher doses of the drug impaired acquisition of the learned response. To show the effect of the GABAergic system on acquisition, GABAA receptor agonists and antagonists were challenged against 0.2 mg/kg of physostigmine. 3. Administration of the GABAA receptor agonist muscimol but not the GABAB receptor agonist baclofen decreased the acquisition of the learned task. However, the improvement induced by physostigmine (0.2 mg/kg) was decreased by both muscimol and baclofen. A combination of both agonists caused a higher inhibitory effect on the physostigmine response. 4. Pretreatment of animals with the higher doses of GABAA receptor antagonists bicuculline and picrotoxin but not the GABAB receptor antagonist phaclofen impaired learning. Both the GABAA and GABAB receptor antagonists reduced the learning improvement induced by physostigmine. The inhibitory effects of the GABAA and GABAB receptor antagonists are lost when combined together. 5. Bicuculline, picrotoxin or phaclofen increased the impairment of learning induced by muscimol, whereas a combination of either of the antagonists with baclofen did not alter the learning. The GABAA antagonists reduced the inhibitory effect of muscimol, whereas a higher dose of phaclofen increased the inhibition of the physostigmine response induced by muscimol and baclofen on physostigmine-induced learning improvement. 6. Phaclofen decreased but a higher dose of bicuculline increased the baclofen-induced inhibition of physostigmine effect. 7. It is concluded that both GABAA and GABAB activation inhibit improvement of acquisition induced by physostigmine.

Animals↗

Impaired spatial learning in aged rats is associated with loss of p75-positive neurons in the basal forebrain.

We investigated age-related changes in the number and size of neurons positive for the p75 neurotrophin receptor in the cholinergic basal forebrain of female Dark Agouti rats. Since the integrity of these neurons is known to be closely associated with performance in tests of spatial learning ability, we also investigated the incidence of age-related spatial learning impairments, using the Barnes maze. Spatial learning impairments occurred with increasing frequency with age. No rats showed impairment at six months, but 50% were impaired at 14 months and 71% at 26 months. There was no correlation between age and decreased number of p75-positive neurons in the rostral basal forebrain, which consists of the medial septum and vertical limb of the diagonal band of Broca. In the caudal basal forebrain, which consists of the horizontal limb and the nucleus of Meynert, there was a 13% reduction in the number of p75-positive neurons at 17 months compared to six months, and a 30% reduction at 26 months. There was a strong correlation between the presence of spatial learning impairment and a reduction in the number of p75-positive neurons. This correlation was most evident in the rostral basal forebrain, but was also present in the caudal basal forebrain. In the rostral basal forebrain, all learning impaired rats had fewer p75-positive neurons than the average number in unimpaired rats. A close correspondence between the presence of p75 and choline acetyltransferase was evident in basal forebrain neurons of learning-impaired and unimpaired rats. Gross pathological changes to the morphology of p75-positive neurons were relatively frequent in learning-impaired rats. These changes consisted of hypertrophy, appearance of vacuoles, and marginalisation of the cytoplasm. The results indicate the susceptibility of p75-positive neurons to degenerative changes with aging, and show that the loss of these neurons in the basal forebrain was strongly correlated with impairment in spatial learning.

Age Factors↗

Modeling functions of striatal dopamine modulation in learning and planning.

The activity of midbrain dopamine neurons is strikingly similar to the reward prediction error of temporal difference reinforcement learning models. Experimental evidence and simulation studies suggest that dopamine neuron activity serves as an effective reinforcement signal for learning of sensorimotor associations in striatal matrisomes. In the current study, we simulate dopamine neuron activity with the extended temporal difference model of Pavlovian learning and examine the influences of this signal on medium spiny neurons in striatal matrisomes. The modeled influences include transient membrane effects of dopamine D(1) receptor activation, dopamine-dependent long-term adaptations of corticostriatal transmission, and effects of dopamine on rhythmic fluctuations of the membrane potential between an elevated "up-state" and a hyperpolarized "down-state". The most dominant activity in the striatal matrisomes is assumed to elicit behaviors via projections from the basal ganglia to the thalamus and the cortex. This "standard model" performs successfully when tested for sensorimotor learning and goal-directed behavior (planning). To investigate the contributions of our model assumptions to learning and planning, we test the performance of several model variants that lack one of these mechanisms. These simulations show that the adaptation of the dopamine-like signal is necessary for sensorimotor learning and planning. Sensorimotor learning requires dopamine-dependent long-term adaptation of corticostriatal transmission. Lack of dopamine-like novelty responses decreases the number of exploratory acts, which impairs planning capabilities. The model loses its planning capabilities if the dopamine-like signal is simulated with the original temporal difference model, because the original temporal difference model does not form novel associative chains. Transient membrane effects of the dopamine-like signal on striatal firing substantially shorten the reaction time in the planning task. The capability for planning is improved by influences of dopamine on the durations of membrane potential fluctuations and by manipulations that prolong the reaction time of the model. These results suggest that responses of dopamine neurons to conditioned stimuli contribute to sensorimotor reward learning, novelty responses of dopamine neurons stimulate exploration, and transient dopamine membrane effects are important for planning.

Animals↗

A molecular mechanism for stabilization of learning-induced synaptic modifications.

Olfaction is a principal sensory modality in rodents, and rats quickly learn to discriminate between odors and to associate odor with reward. Here we show that such olfactory discrimination (OD) learning consists of two phases with distinct cellular mechanisms: an initial NMDAR-sensitive phase in which the animals acquire a successful behavioral strategy (rule learning), followed by an NMDAR-insensitive phase in which the animals learn to distinguish between individual odors (pair learning). Rule learning regulates the composition of synaptic NMDARs in the piriform cortex, resulting in receptors with a higher complement of the NR2a subunit protein relative to NR2b. Rule learning also reduces long-term potentiation (LTP) induced by high-frequency stimulation of the intracortical axons in slices of piriform cortex. As NR2a-containing NMDARs mediate shorter excitatory postsynaptic currents than those containing NR2b, we suggest that learning-induced regulation of NMDAR composition constrains subsequent synaptic plasticity, thereby maintaining the memory encoded by experience.

Animals↗

Representation of well-learned information in the monkey hippocampus.

In the neocortex, extensive training results in enhanced neuronal selectivity for learned stimuli relative to novel stimuli. This enhanced selectivity has been taken as evidence for learning-related plasticity. Much less is known, in contrast, about the representation of well-learned information in the hippocampus. In this study, we examined the responses of individual hippocampal neurons to well-learned and novel stimuli presented in the context of an associative learning task. There was no difference in the response magnitude or visual response latency of hippocampal neurons to the well-learned and novel stimuli. In contrast, hippocampal neurons responded significantly more selectively to the well-learned stimuli relative to the novel stimuli. These findings show that hippocampal cells, like neocortical cells, show greater selectivity to well-learned stimuli compared to novel stimuli.

Animals↗

Skill learning in mirror reading: how repetition determines acquisition.

Practice makes perfect, but the role of repetitions in skill learning is not yet fully understood. For example, given a similar number of trials on a given task, it is debated whether repeating and non-repeating items are learned by the same neural process. When one is given training with both types of items--does one learn two separate skills, or only one? Here we show, using a mirror reading task, that practice trials with trial-unique words, and practice trials with repeated words, count towards learning to a different degree. There was no interaction between the time-course of learning repeated and unique words even within the same individuals given mixed training. While repeated words were learned faster than unique words, the repetitions-dependent gains diminished with training beyond a small number of repetitions. Moreover, the gains in performance could not be accounted for solely by the number of repetitions, as assumed by power-law models of learning; rather, the passage of time was a critical factor. Finally, our results suggest that although both repeated and new words were learned by both declarative and procedural memory mechanisms, even a single repetition of specific words could lead to the establishment of a selective differential representation in memory. The results are compatible with the notion of a repetition-sensitive process, triggered by specific repeating events. This 'repetition counter' may be a critical trigger for the effective formation of procedural as well as some type of declarative memory.

Adolescent↗

Interactions of the hippocampal system and the prefrontal cortex in learning language-like rules.

One of the most influential views on the hippocampal function suggests that this brain region is critically involved in relational memory processing, that is, binding converging inputs to mediate the representation of relationships among the constituents of episodes. It has been proposed that this binding is automatic and obligatory during learning and remembering In addition, neuroimaging studies have highlighted the importance of the prefrontal cortex, in learning, memory, and language processing. However, the posited importance of hippocampal-prefrontal interaction remains to be empirically tested. In the present study we used functional magnetic resonance imaging to examine in detail this interaction by assessing learning-related changes in hemodynamic activity during artificial language acquisition. It has been shown previously that artificial grammar systems might be learned by evaluating pattern-based relations in word sequences and generalizing beyond specific word order, that is, rule abstraction. During scanning, participants learned an artificial language whose miniature grammar meets the universal principles of a natural language. Increased proficiency level of the artificial language is associated with decreased left hippocampal activity. In contrast, we observed an increased recruitment of the left inferior frontal gyrus (Broca's area), a region that contributes to syntax processing in natural language. The present results, therefore, indicate a learning-related change in brain circuitry underlying relational processes of language learning, with a transition from a similarity-based learning system in the medial temporal lobes to a language-related processing system in the left prefrontal cortex.

Adult↗

Cognitive performance in learning disabled children with and without epilepsy.

Cognitive functioning and educational achievement were examined in learning disabled children with epilepsy (n = 65) and without epilepsy (n = 122) in order to explore whether children with epilepsy show unique types of learning problems, different from those in other learning disabled children. The learning disabled children with epilepsy tended to perform better on tests of verbal intelligence, certain achievement-related abilities and were better in one area of academic achievement, i.e. spelling. Despite their superior performance in these areas, the learning disabled children with epilepsy were slower than those without epilepsy and regular education controls (n = 100) on simple auditory and visual reaction tasks as well as on a multiple decision reaction task and a visual searching task. The results obtained with the school achievement tasks provide no clear evidence for specific types of learning impairment in children with epilepsy. Learning disabled children with epilepsy do not appear to have educational needs different from those of other learning disabled children.

Attention↗

Learning styles of baccalaureate nursing students and attitudes toward theory-based nursing.

The purpose of this study was to investigate personal and environmental factors related to undergraduate and post-RN nursing students' attitudes toward theory-based nursing from Kolb's experimental learning theory perspective. The study is part of a larger project designed to test aspects of Kolb's theory in the nursing population. Hypotheses about relationships among learning styles, perception of environmental press, experience in nursing, attitudes toward theory-based nursing, preferred nursing theory, and preferred method of learning theory were proposed for investigation. Seventy-six post-RN and 121 upper-level generic baccalaureate nursing students each completed two measures of personal learning style, a measure of perception of environmental press of nursing learning environments, and a nursing theories questionnaire. Learning style and environmental press perceptions were found to be significantly related to attitudes toward theory-based nursing. Concrete learners and subjects who perceived nursing environments to be predominantly concrete were significantly less positive toward theory-based nursing than abstract learners. Experience in nursing was found to be related to perception of environmental press. Learning style was not found to be significantly related to preferred method of learning nursing theories nor to preferred nursing theory for practice. Implications for nursing education are discussed.

Adult↗

Quantitative trait loci associated with reversal learning and latent inhibition in honeybees (Apis mellifera).

A study was conducted to identify quantitative trait loci (QTLs) that affect learning in honeybees. Two F1 supersister queens were produced from a cross between two established lines that had been selected for differences in the speed at which they reverse a learned discrimination between odors. Different families of haploid drones from two of these F1 queens were evaluated for two kinds of learning performance--reversal learning and latent inhibition--which previously showed correlated selection responses. Random amplified polymorphic DNA markers were scored from recombinant, haploid drone progeny that showed extreme manifestations of learning performance. Composite interval mapping procedures identified two QTLs for reversal learning (lrn2 and lrn3: LOD, 2.45 and 2.75, respectively) and one major QTL for latent inhibition (lrn1: LOD, 6.15). The QTL for latent inhibition did not map to either of the linkage groups that were associated with reversal learning. Identification of specific genes responsible for these kinds of QTL associations will open up new windows for better understanding of genes involved in learning and memory.

Animals↗