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Impairment of mossy fiber long-term potentiation and associative learning in pituitary adenylate cyclase activating polypeptide type I receptor-deficient mice.

The pituitary adenylate cyclase activating polypeptide (PACAP) type I receptor (PAC1) is a G-protein-coupled receptor binding the strongly conserved neuropeptide PACAP with 1000-fold higher affinity than the related peptide vasoactive intestinal peptide. PAC1-mediated signaling has been implicated in neuronal differentiation and synaptic plasticity. To gain further insight into the biological significance of PAC1-mediated signaling in vivo, we generated two different mutant mouse strains, harboring either a complete or a forebrain-specific inactivation of PAC1. Mutants from both strains show a deficit in contextual fear conditioning, a hippocampus-dependent associative learning paradigm. In sharp contrast, amygdala-dependent cued fear conditioning remains intact. Interestingly, no deficits in other hippocampus-dependent tasks modeling declarative learning such as the Morris water maze or the social transmission of food preference are observed. At the cellular level, the deficit in hippocampus-dependent associative learning is accompanied by an impairment of mossy fiber long-term potentiation (LTP). Because the hippocampal expression of PAC1 is restricted to mossy fiber terminals, we conclude that presynaptic PAC1-mediated signaling at the mossy fiber synapse is involved in both LTP and hippocampus-dependent associative learning.

Animals↗

The hippocampus and appetitive Pavlovian conditioning: effects of excitotoxic hippocampal lesions on conditioned locomotor activity and autoshaping.

The hippocampus (HPC) is known to be critically involved in the formation of associations between contextual/spatial stimuli and behaviorally significant events, playing a pivotal role in learning and memory. However, increasing evidence indicates that the HPC is also essential for more basic motivational processes. The amygdala, by contrast, is important for learning about the motivational significance of discrete cues. This study investigated the effects of excitotoxic lesions of the rat HPC and the basolateral amygdala (BLA) on the acquisition of a number of appetitive behaviors known to be dependent on the formation of Pavlovian associations between a reward (food) and discrete stimuli or contexts: (1) conditioned/anticipatory locomotor activity to food delivered in a specific context and (2) autoshaping, where rats learn to show conditioned discriminated approach to a discrete visual CS+. While BLA lesions had minimal effects on conditioned locomotor activity, hippocampal lesions facilitated the development of both conditioned activity to food and autoshaping behavior, suggesting that hippocampal lesions may have increased the incentive motivational properties of food and associated conditioned stimuli, consistent with the hypothesis that the HPC is involved in inhibitory processes in appetitive conditioning.

Amygdala↗

Neuropsychological functioning in nonreferred siblings of children with attention deficit/hyperactivity disorder.

The goal of this study was to assess neuropsychological functioning in nonreferred siblings of children with attention deficit/hyperactivity disorder (ADHD). Participants were 156 siblings of ADHD probands with (N = 40) and without (N = 116) ADHD (according to criteria of the Diagnostic and Statistical Manual of Mental Disorders (3rd edition, revised; American Psychiatric Association, 1987) and 118 siblings of non-ADHD normal controls of similar age, IQ, and grade level. Information on attention, executive, and memory functions was obtained in a standardized manner without knowledge of clinical status. Compared with siblings of controls, siblings with ADHD were significantly impaired on the Stroop test and on verbal learning and memory. In contrast, siblings without ADHD were similar to controls on virtually all measures. These data suggest that some executive, attention, and verbal learning deficits are found in nonreferred individuals with ADHD but that neuropsychological deficits are unlikely to constitute an endophenotype to ADHD.

Adolescent↗

Psychometric characteristics of the conceptions of mathematics questionnaire.

This study describes the psychometric characteristics of the 19-item Conceptions of Mathematics Questionnaire for a total of 158 students (86 women and 72 men). The coefficient alpha of internal consistency reliability was .75. Principal components analysis with varimax rotation indicated a two-component solution could be extracted. The two theoretically meaningful dimensions were fragmented conceptions (alpha = .80) and cohesive conceptions (alpha = .80). The former entails seeing mathematics as number rules and formulae to be used to solve problems. Students who hold this conception use rote learning and memorization. In contrast, the latter entails seeing mathematics as a complex logical system for solving complex problems. Students with such a conception approach learning to attain, develop, and apply knowledge.

Adolescent↗

Evolution of learning in three aplysiid species: differences in heterosynaptic plasticity contrast with conservation in serotonergic pathways.

We investigated the neurobiological basis of variation in sensitization between three aplysiid species: Aplysia californica, Phyllaplysia taylori and Dolabrifera dolabrifera. We tested two different forms of sensitization induced by a noxious tail shock: local sensitization, expressed near the site of shock, and general sensitization, tested at remote sites. Aplysia showed both local and general sensitization, whereas Phyllaplysia demonstrated only local sensitization, and Dolabrifera lacked both forms of learning. We then investigated a neurobiological correlate of sensitization, heterosynaptic modulation of sensory neuron excitability by tail-nerve stimulation. We found (1) an increase in sensory neuron (SN) excitability after both ipsilateral and contralateral nerve stimulation in Aplysia, (2) a smaller and shorter-lasting increase in Phyllaplysia, and (3) no effect in Dolabrifera. Because sensitization in Aplysia is strongly correlated with serotonergic (5-HT) neuromodulation, we hypothesized that the observed interspecific variation in sensitization and SN neuromodulation might be correlated with variation in the anatomy and/or functional response of the serotonergic system. However, using immunohistochemistry, we found that all three species showed a similar pattern of 5-HT innervation. Furthermore, they also showed comparable 5-HT release evoked by tail-nerve shock, as measured with chronoamperometry. These observations indicate that interspecific variation in learning is correlated with differences in SN heterosynaptic plasticity within a background of evolutionary conservation in the 5-HT neuromodulatory pathway. We thus hypothesize that evolutionary changes in learning phenotype do not involve modifications of the 5-HT pathway per se, but rather, changes in the response of SNs to the activation of this or other neuromodulatory pathways upon noxious stimulation.

Animals↗

Operant learning and differential-reinforcement-of-low-rate 36-s responding in 5-HT1A and 5-HT1B receptor knockout mice.

Previous studies with mice lacking 5-HT(1A) (1AKO) and 5-HT(1B) (1BKO) receptors in hippocampus-dependent learning and memory paradigms, suggest that these receptors play an important role in learning and memory, although their precise role is unclear. In the present study, 1AKO and 1BKO mice were studied in operant behavioural paradigms of decision making and response inhibition, to further study the putative involvement of these receptors in prefrontal cortex-dependent learning and memory. Moreover, because 1AKO mice have been shown to exhibit an antidepressant-like phenotype and 1BKO mice to be more impulsive in ethological studies, mice were trained in a differential-reinforcement-of-low-rates (DRL) procedure. Overall, results indicate that 1AKO and 1BKO mice display subtle differences in operant paradigms of decision making and response inhibition compared to wild type (WT) mice. In addition, when responding under a DRL 36-s schedule had stabilised, 1BKO mice showed a phenotype indicative of increased impulsivity, whereas 1AKO mice did not differ from WT mice. In conclusion, 5-HT(1B) receptors appear to play an important role in impulsivity and a minor role in prefrontal cortex-dependent learning and memory as shown by the results obtained in serial reversal learning and extinction. In contrast, 5-HT(1A) receptors appear to be involved in facilitation of autoshaping, but their role in impulsivity and prefrontal cortex-dependent learning and memory appears to be limited.

Animals↗

Different roles for amygdala central nucleus and substantia innominata in the surprise-induced enhancement of learning.

Within most modern learning theories, the discrepancy between expected and obtained outcomes ("prediction error" or "surprise") is a critical determinant of the acquisition of learned associations. The results of studies from many laboratories show that the surprising omission of an expected event may enhance attention to stimuli that remain present, such that subsequent learning about those stimuli is enhanced. A series of reports from our laboratories demonstrated that these surprise-induced enhancements of stimulus associability depend on circuitry that includes the amygdala central nucleus (CeA), the cholinergic neurons in the sublenticular substantia innominata/nucleus basalis magnocellularis (SI/nBM), as well as certain cortical projections of these latter neurons. In this study, we found very different roles for CeA and SI/nBM in surprise-induced enhancements of stimulus associability. In four experiments that used transient inactivation techniques, we found that surprise-induced enhancement of subsequent learning about a stimulus depended on intact CeA function at the time of surprise but not when more rapid learning was subsequently expressed. In contrast, normal SI/nBM function was critical to the expression of enhanced learning but was not necessary when surprise was induced. These data suggest that these two components of the so-called "extended amygdala" serve distinct roles in the encoding and retrieval of information used in modulating attention to stimuli in associative learning. Additional circuitry linking these brain regions may also be important in the maintenance of that information.

Amygdala↗

The mnemonic mechanisms of errorless learning.

Errorless learning enhances memory relative to errorful, trial-and-error learning, but the extent to which this advantage relies on implicit or explicit memory processes is not clear. Previous attempts to determine the mnemonic mechanisms of errorless learning have relied on contrasts between patient groups or between tasks, but both approaches are problematic. In this study, healthy younger and older adults were engaged in errorless or errorful learning using a process dissociation procedure that provides separate estimates of explicit recollection and implicit familiarity within-subjects and within-task (Hay & Jacoby, 1996). Consistent with much prior research, we found an age-related decrement in recollection, but age-invariance in familiarity. In the young adults, errorless learning reduced the misleading familiarity of prior errors, but this benefit was offset by the non-elaborative nature of the errorless learning condition that also reduced recollection. In the older adults, who are less able to oppose familiarity-based errors because of their lower recollection, errorless learning only reduced the misleading impact of previous errors. Our results support Baddeley and Wilson's (1994) position that the errorless learning effect is mediated by implicit memory processes: individuals with reduced explicit memory benefit from errorless learning because errorless learning bypasses the need to engage explicit error elimination processes. We do not recommend standard errorless learning for individuals with intact explicit memory, such as students trying to learn information in preparation for an examination.

Adolescent↗

A novel method for assessing contrast sensitivity in the beagle dog is sensitive to age and an antioxidant enriched food.

Tasks requiring visual discrimination are commonly used in assessment of canine cognitive function. However, little is known about canine visual processing, and virtually nothing is known about the effects of age on canine visual function. This study describes a novel behavioural method developed to assess one aspect of canine visual function, namely contrast sensitivity. Four age groups (young, middle aged, old, and senior) were studied. We also included a group of middle aged to old animals that had been maintained for at least 4 years on a specially formulated food containing a broad spectrum of antioxidants and mitochondrial cofactors. Performance of this group was compared with a group in the same age range maintained on a control diet. In the first phase, all animals were trained to discriminate between two high contrast shapes. In the second phase, contrast was progressively reduced by increasing the luminance of the shapes. Performance decreased as a function of age, but the differences did not achieve statistical significance, possibly because of a small sample size in the young group. All age groups were able to acquire the initial discrimination, although the two older age groups showed slower learning. Errors increased with decreasing contrast with the maximal number of errors for the 1% contrast shape. Also, all animals on the antioxidant diet learned the task and had significantly fewer errors at the high contrast compared with the animals on the control diet. The initial results suggest that contrast sensitivity deteriorates with age in the canine while form perception is largely unaffected by age.

Aging↗

Effects of anterior temporal lobectomy on cognitive function.

Sixty-three patients with intractable partial complex epilepsy were treated by anterior temporal lobectomy for seizure control. Psychometric studies before and after operation documented cognitive function and evaluated the effects of operation on cognition. The mean follow-up period was 7.7 months. Sixty-two of 63 patients had improved seizure control; 49 (78%) were seizure free. Operation had different effects on cognitive abilities in those with right vs. left temporal lobe excisions. Although both groups maintained summary IQ scores in the average range, after operation the left temporal group was less efficient on language-dependent cognitive tasks, particularly those that involved complex learning and memory. In contrast, persons who had right temporal ablations were either unchanged or slightly better cognitively after operation. Future research and clinical evaluations should focus on the components of the learning and memory processes when the ramifications of temporal lobe ablations on cognitive function are studied.

Adult↗

Nonverbal amnesia and asymmetric cerebral lesions following encephalitis.

Global amnesia after herpes simplex encephalitis has been typically associated with lesions of anterior and medial temporal lobe, inferior and medial frontal lobe, and insula. The neuropathologic correlates of this disease are usually considered to be bilateral and similar across cases. We describe a 27-year-old woman whose chronic amnesia and cerebral lesions after viral encephalitis indicate a different pattern. Two features distinguish her presentation: (1) markedly asymmetric lesions extensively involving the right temporal lobe but sparing almost all of the same structures on the left and (2) severe compromise of nonverbal learning and a nonverbal retrograde amnesia in contrast to disproportionately small impairments of verbal learning and retention. The findings suggest that encephalitis patients cannot be treated as a homogeneous group and that detailed analysis of variability in their anatomic lesions may be an important explanatory factor in neural accounts of these severe human amnesias.

Adolescent↗

Global perception in small brains: topological pattern recognition in honey bees.

A series of experiments with honey bees demonstrate that their small brains nevertheless possess the ability for topological perception. Bees rapidly learned to discriminate patterns that are topologically different, and they generalized the learned cue to other novel patterns. By contrast, discrimination of topologically equivalent patterns was learned much more slowly and not as well. Thus, although the global nature of topological properties makes their computation difficult, topology may be a fundamental component of the vocabulary by which visual systems represent and characterize objects.

Animals↗

Context fear learning in the absence of the hippocampus.

Lesions of the rodent hippocampus invariably abolish context fear memories formed in the recent past but do not always prevent new learning. To better understand this discrepancy, we thoroughly examined the acquisition of context fear in rats with pretraining excitotoxic lesions of the dorsal hippocampus. In the first experiment, animals received a shock immediately after placement in the context or after variable delays. Immediate shock produced no context fear learning in lesioned rats or controls. In contrast, delayed shock produced robust context fear learning in both groups. The absence of fear with immediate shock occurs because animals need time to form a representation of the context before shock is presented. The fact that it occurs in both sham and lesioned rats suggests that they learn about the context in a similar manner. However, despite learning about the context in the delay condition, lesioned rats did not acquire as much fear as controls. The second experiment showed that this lesion-induced deficit could be overcome by increasing the number of conditioning trials. Lesioned animals learned normally after multiple shocks, regardless of freezing level or trial spacing. The last experiment showed that animals with complete hippocampus lesions could also learn about the context, although the same lesions produced devastating retrograde amnesia. These results demonstrate that alternative systems can acquire context fear but do so less efficiently than the hippocampus.

Amnesia, Retrograde↗

Duration differences: attentional demand or time error?

Underwood (1975) has used judgments of duration to compare the attentional demands of learning and recall. His study is critically discussed and two further experiments are reported. In experiment 1 subjects spent 50 s learning a list of words and a further 50 s either trying to recall them or learning another list. In contrast to Underwood's subjects both groups judged the first interval to have been longer than the second. In experiment 2 three separate groups of subjects spent 50 s learning a list of items (nonsense syllables, unrelated words, or related words, as in Underwood's experiment) and then a further 50 s trying to recall them. Once again the first interval was judged to have been of greater duration. The implications of these findings for the use of duration judgments as a measure of attentional demand are discussed.

Attention↗

Differential effects of anterior and posterior insular cortex lesions on the acquisition of conditioned taste aversion and spatial learning.

In this study, we evaluated the effects of NMDA-induced lesions in different sites of the insular cortex of the rat on the acquisition of conditioned taste aversion and spatial learning in the Morris water maze. The lesions were produced by bilateral microinjections of NMDA in the insular cortex at +3.7 mm (Anterior group), +1.7 mm (Central group), and -0.3 mm (Posterior group) anteroposterior from bregma. The results showed that the central and posterior, but not the anterior, lesions disrupted the acquisition of water maze learning as measured by the high latency to reach the target. In contrast, the conditioned taste aversion learning was disrupted by lesions in the central but not in the anterior or posterior insular cortex. These data confirm functional heterogeneity of the insular cortex and demonstrate that the more caudal parts are only necessary for acquisition of the water maze task, while the central insular cortex is crucial for the acquisition of both the conditioned taste aversion learning and the Morris water maze.

Animals↗

The POP learning algorithms: reducing work in identifying fuzzy rules.

A novel fuzzy neural network, the Pseudo Outer-Product based Fuzzy Neural Network (POPFNN), and its two fuzzy-rule-identification algorithms are proposed in this paper. They are the Pseudo Outer-Product (POP) learning and the Lazy Pseudo Outer-Product (LazyPOP) leaning algorithms. These two learning algorithms are used in POPFNN to identify relevant fuzzy rules. In contrast with other rule-learning algorithms, the proposed algorithms have many advantages, such as being fast, reliable, efficient, and easy to understand. POP learning is a simple one-pass learning algorithm. It essentially performs rule-selection. Hence, it suffers from the shortcoming of having to consider all the possible rules. The second algorithm, the LazyPOP learning algorithm, truly identifies the fuzzy rules which are relevant and does not use a rule-selection method whereby irrelevant fuzzy rules are eliminated from an initial rule set. In addition, it is able to adjust the structure of the fuzzy neural network. The proposed LazyPOP learning algorithm is able to delete invalid feature inputs according to the fuzzy rules that have been identified. Extensive experimental results and discussions are presented for a detailed analysis of the proposed algorithms.

Algorithms↗

Perception and production of approximant consonants by normal and articulation-delayed preschool children.

Disagreement exists concerning the relationship between the perception of phonetic contrasts and their production by both normal and articulation-delayed children. The perception of three approximant consonant contrasts (/w/-/r/, /w/-/l/, /r/-/l/) was examined in two groups of 3-year-old children: normal children who did and did not articulate /r/ and /l/ correctly and articulation-delayed children who misarticulated /r/ and /l/. Perception was assessed in a two-choice forced-choice identification task in which the subjects heard a word and pushed a button lighting a picture corresponding to the word. In general, normally developing children were highly accurate in their perception of all three contrasts, but there was more variability in /w/-/l/ perceptual performance among the children who neutralized the /w/-/l/ contrast. Articulation-delayed children displayed a wider range of production patterns and were more variable in their perceptual performance than normally developing children. Results suggest than normally developing children learn to perceive approximant contrasts prior to 3 years of age. However, some but not all articulation-delayed 3-year-old children may still make errors in the perception of approximants.

Articulation Disorders↗

Conditioning of leg position in normal and mutant Drosophila.

Individual Drosophila melanogaster, with or without heads, can be trained to lift their legs to avoid electric shock. This behavior is similar to the operant conditioning previously demonstrated in intact and headless cockroaches. More than 90% of headless wild-type flies learned to our criterion. In contrast, three mutants (dunce, cabbage, and turnip), originally selected for failure to learn in an olfactory discrimination paradigm, tended to perform poorly in this new learning situation. The difference in learning behavior between normal and mutant flies is distinguishable in individuals and may be useful for mosaic analysis.

Animals↗