Differential regional expression of brain-derived neurotrophic factor following olfactory fear learning

We examined brain-derived neurotrophic factor (BDNF) mRNA expression across the olfactory system following fear conditioning. Mice received 10 pairings of odor with footshock or equivalent unpaired odors and shocks. We found increased BDNF mRNA in animals receiving paired footshocks in the multiple regions examined including the posterior piriform cortex (PPC) and basolateral amygdala (BLA). This was in contrast to the unpaired and odor-alone treatments, where BDNF mRNA was increased in the olfactory bulb (OB) and anterior piriform cortex (APC) only, but not the higher olfactory areas. We propose that odor exposure increases expression of BDNF in the OB and APC while the PPC and BLA increase BDNF mRNA only when associative learning occurs.     

Voluntary exercise ameliorates cognitive deficits in morphine dependent rats: the role of hippocampal brain-derived neurotrophic factor

Chronic exposure to opiates impairs spatial learning and memory. Given the well-known beneficial effects of voluntary exercise on cognitive functions, we investigated whether voluntary exercise would ameliorate the cognitive deficits that are induced by morphine dependence. If an effect of exercise was observed, we aimed to investigate the possible role of hippocampal brain-derived neurotrophic factor (BDNF) in the exercise-induced enhancement of learning and memory in morphine-dependent rats. The rats were injected with bi-daily doses (10mg/kg, at 12h intervals) of morphine over a period of 10 days of voluntary exercise. Following these injections, a water maze task was performed twice a day for five consecutive days, followed by a probe trial 2 days later. A specific BDNF inhibitor (TrkB-IgG chimera) was used to block the hippocampal BDNF action during the 10 days of voluntary exercise. We found that voluntary exercise blocked the ability of chronic morphine to impair spatial memory retention. A blockade of the BDNF action blunted the exercise-induced improvement of spatial memory in the dependent rats. Moreover, the voluntary exercise diminished the severity of the rats' dependency on morphine. This study demonstrates that voluntary exercise ameliorates, via a TrkB-mediated mechanism, the cognitive deficits that are induced by chronic morphine. Thus, voluntary exercise might be a potential method to ameliorate some of the deleterious behavioral consequences of the abuse of morphine and other opiates.     

The role of brain-derived neurotrophic factor genotype, parental depression, and relationship discord in predicting early-emerging negative emotionality

The brain-derived neurotrophic factor (BDNF) gene is a plausible candidate for early-emerging negative emotionality (NE), and evidence suggests that the effects of this gene may be especially salient in the context of familial risk for child maladjustment. We therefore examined whether the single-nucleotide polymorphism producing a valine-to-methionine substitution at codon 66 (val66met) of the BDNF gene was associated with childhood NE, in the context of parental depression and relationship discord. A sample of 413 three-year-old children was assessed for NE using standardized laboratory measures. The children's parents completed clinical interviews as well as a measure of marital satisfaction. Children with at least one BDNF methionine (met) allele exhibited elevated NE when a parent had a history of depressive disorder or when relationship discord was reported by a parent. In contrast, this allele was associated with especially low NE when parental depression was absent and when the parental relationship was not discordant. Our findings suggest that the BDNF met allele confers increased child sensitivity to both positive and negative familial influences.     

Insulin receptor signaling in long-term memory consolidation following spatial learning

Evidence has shown that the insulin and insulin receptor (IR) play a role in cognitive function. However, the detailed mechanisms underlying insulin's action on learning and memory are not yet understood. Here we investigated changes in long-term memory-associated expression of the IR and downstream molecules in the rat hippocampus. After long-term memory consolidation following a water maze learning experience, gene expression of IR showed an up-regulation in the CA1, but a down-regulation in the CA3 region. These were correlated with a significant reduction in hippocampal IR protein levels. Learning-specific increases in levels of downstream molecules such as IRS-1 and Akt were detected in the synaptic membrane accompanied by decreases in Akt phosphorylation. Translocation of Shc protein to the synaptic membrane and activation of Erk1/2 were also observed after long-term memory formation. Despite the clear memory-correlated alterations in IR signaling pathways, insulin deficits in experimental diabetes mellitus (DM) rats induced by intraperitoneal injections of streptozotocin resulted in only minor memory impairments. This may be due to higher glucose levels in the DM brain, and to compensatory mechanisms from other signaling pathways such as the insulin-like growth factor-1 receptor (IGF-1R) system. Our results suggest that insulin/IR signaling plays a modulatory role in learning and memory processing, which may be compensated for by alternative pathways in the brain when an insulin deficit occurs.     

Late expression of brain-derived neurotrophic factor in the amygdala is required for persistence of fear memory

In many instances, increase in neuronal activity can induce biphasic secretion of a modulator. The initial release of the modulator triggers the induction of synaptic plasticity, whereas the second-phase release reinforces the efficacy of synaptic transmission and growth of dendrites and axons. In this study, we showed that fear conditioning not only induced the first but also a second peak of brain-derived neurotrophic factor (BDNF) expression. Fluorescent immunohistostaining confirmed that BDNF expression increased at 1 and 12 h after conditioning and returned to baseline at 30 h after conditioning. Mature BDNF expression increased in a similar manner. TrkB-IgG or K252a infusion before training impaired fear memory on days 1 and 7 after training. In contrast, TrkB-IgG or K252a infusion 9 h after fear conditioning did not affect memory retention on day 1 after training but impaired fear memory on day 7 after training. Fear conditioning significantly enhanced Zif268 expression in the amygdala at 12 h after training; this enhanced expression was completely inhibited by TrkB-IgG infusion 9 h after training. The level of growth-associated protein 43 (GAP-43), a marker of newly formed synapses, in the amygdala increased 7 days after fear conditioning. Moreover, conditioned rats had higher AMPA/NMDA ratio than unpaired rats. These results suggest that consolidated memory could be continuously modulated by previous molecular changes produced during memory acquisition.     

From children's hands to adults' ears: gesture's role in the learning process

Children can express thoughts in gesture that they do not express in speech--they produce gesture-speech mismatches. Moreover, children who produce mismatches on a given task are particularly ready to learn that task. Gesture, then, is a tool that researchers can use to predict who will profit from instruction. But is gesture also useful to adults who must decide how to instruct a particular child? We asked 8 adults to instruct 38 third- and fourth-grade children individually in a math problem. We found that the adults offered more variable instruction to children who produced mismatches than to children who produced no mismatches--more different types of instructional strategies and more instructions that contained two different strategies, one in speech and the other in gesture. The children thus appeared to be shaping their own learning environments just by moving their hands. Gesture not only reflects a child's understanding but can play a role in eliciting input that could shape that understanding. As such, it may be part of the mechanism of cognitive change.     

Lesions of the entorhinal cortex impair acquisition of hippocampal-dependent trace conditioning

Rabbits with the electrolytic lesions of bilateral entorhinal cortex (EC) were trained with the hippocampal-dependent trace conditioning of the nictitating membrane response. The multiple-unit activity of the hippocampal CA1 region was recorded during conditioning. The conditioned stimulus was a tone (1 kHz, 85 dB, 200-ms duration), the unconditioned stimulus was a corneal air puff (3 psi, 150-ms duration), and the interstimulus interval was 750 ms. The EC-lesioned animals showed only 30% conditioned response (CR) by the ninth session while the sham-operated animals showed above 80% CR. The lesioned animals did not show learning-related changes in the hippocampal activity. When the training was switched to the 300-ms interstimulus interval trace conditioning, both groups learned above 80% CR. The EC-lesioned animals, however, showed less learning-related activity in the hippocampus than the sham-operated animals. These results suggest that the development of the learning-related activity in the hippocampus depends on the intact EC, and that the EC may provide a possible pathway conveying learning information from the cerebellum or cerebral cortex to the hippocampus during the trace conditioning.     

The role of implicit learning in the acquisition of generative knowledge

This paper reports two experiments using a modified artificial grammar paradigm to study the acquisition of generative knowledge. It employs a starship game and a computerized form of motherese to study acquisition of generative knowledge of a grammar. It was found that initial exposure to a small set of representative cases and an opportunity to organize the cases enhanced ability to generate grammatical strings. Neither seeing a large number of cases nor building a conceptual model of the grammar enhanced acquisition of generative knowledge. However, building a conceptual model did increase learners’ confidence in their ability to generate strings. The quality of strings generated by learners remained fairly constant across attempts, suggesting that their performance reflects true generative knowledge rather than memories of exemplars.     

From the lexicon to expectations about kinds: a role for associative learning

In the novel noun generalization task, 2 1/2-year-old children display generalized expectations about how solid and nonsolid things are named, extending names for never-before-encountered solids by shape and for never-before-encountered nonsolids by material. This distinction between solids and nonsolids has been interpreted in terms of an ontological distinction between objects and substances. Nine simulations and behavioral experiments tested the hypothesis that these expectations arise from the correlations characterizing early learned noun categories. In the simulation studies, connectionist networks were trained on noun vocabularies modeled after those of children. These networks formed generalized expectations about solids and nonsolids that match children's performances in the novel noun generalization task in the very different languages of English and Japanese. The simulations also generate new predictions supported by new experiments with children. Implications are discussed in terms of children's development of distinctions between kinds of categories and in terms of the nature of this knowledge.     

Epigenetic regulation of reelin and brain-derived neurotrophic factor genes in long-term potentiation in rat medial prefrontal cortex

Epigenetic mechanisms have recently been known to play fundamental roles in the regulation of synaptic plasticity, and learning and memory tasks in many brain regions, such as the hippocampus, the amygdala, the insular cortex. However, epigenetic mechanism in the medial prefrontal cortex (mPFC), also a crucial neural locus for the control of cognition and emotion, is not well known. The present study investigated the epigenetic regulation of two genes, reelin and brain-derived neurotrophic factor (bdnf), both play important roles in neural plasticity, in the mPFC. The data showed that the levels of total DNA methyltransferase (DNMTs), total histone acetyltransferases (HATs), global acetylated histone 3 (H3) and global acetylated histone 4 (H4) were all changed with the induction of long-term potentiation (LTP) in the mPFC, implying that DNA methylation and histone acetylation may involve in synaptic plasticity in the mPFC. The present results further demonstrated that the demethylation status of reelin and bdnf, and acetylated H3 and acetylated H4 at the reelin and the bdnf promoters in the mPFC were enhanced by the delivery of LTP-inducing high-frequency stimulation (HFS). Consistently, infusion of DNMT inhibitor, 5-azacytidine (5-azaC), or histone deacetylases (HDACs) inhibitor, sodium butyrate (NaB), into the mPFC could interfere with LTP-associated demethylation and acetylation of reelin and bdnf genes, and the induction of LTP as well. Long-term retention of trace fear memory, which is dependent on mPFC function, was also altered by administration of these inhibitors into the mPFC. These findings suggest that epigenetic regulation of DNA demethylation and histone acetylation of target genes, such as reelin and bdnf, might underlie the mechanisms of synaptic plasticity and memory retention in the mPFC.     

Influence of brain-derived neurotrophic factor and catechol O-methyl transferase polymorphisms on effects of meditation on plasma catecholamines and stress

Meditation may show differential effects on stress and plasma catecholamines based on genetic polymorphisms in brain-derived neurotrophic factor (BDNF) and catechol O-methyl transferase (COMT). Eighty adults (40 men, 40 women; mean age 26 years) who practiced meditation regularly and 57 healthy control adults (35 men, 22 women; mean age 26 years) participated. Plasma catecholamines (norepinephrine (NE), epinephrine (E), and dopamine (DA)) concentrations were measured, and a modified form of the Stress Response Inventory was administered. The results were analyzed using two-way analysis of covariance (ANCOVA) with control and meditation subjects, gene polymorphism as factors, and meditation duration as the covariate. Two-way ANCOVA showed a significant interaction between control and meditation subjects, and BDNF Val66Met polymorphism on DA/NE+DA/E (p = 0.042) and NE/E+NE/DA (p = 0.046) ratios. A significant interaction was found for control and meditation subjects with COMT Val158Met polymorphism and plasma NE concentrations (p = 0.009). Post hoc ANCOVA in the meditation group, adjusted for meditation duration, showed significantly higher plasma NE concentrations for COMT Met carriers than COMT Val/Val subjects (p = 0.025). Significant differences of stress levels were found between the control and meditation subjects in BDNF Val/Met (p < 0.001) and BDNF Met/Met (p = 0.003), whereas stress levels in the BDNF Val/Val genotype did not differ between the control and meditation groups. This is the first evidence that meditation produces different effects on plasma catecholamines according to BDNF or COMT polymorphisms.     

The role of age of acquisition in memory: effects on judgements of learning and recall

Judgements of learning (JOLs) are self-made predictions of the likelihood that one will later recall information. The influence of stimulus characteristics on JOLs and recall continues to receive attention, yet there are still a number of unexplored lexical word features that may exert an effect on mnemonic processing. Using a standard cue-target paradigm, we focused on the role of word age of acquisition (AoA) and evaluated the role of both cue and target AoA on responses. We replicated the robust delayed-JOL effect and used a novel items analysis approach to examine the relationship between intrinsic word features and accuracy and reaction times for both JOLs and recall. A consistent effect of target AoA was found, even after controlling for a range of covariates previously shown to impact JOLs and recall. These results expand the role of AoA in word processing and suggest that it is a key variable in memory and metacognition; they also support Koriat's (1997) cue utilization framework.     

Chronic social comparison elicits depression- and anxiety-like behaviors and alterations in brain-derived neurotrophic factor expression in male rats

Animal Cognition - Social comparison is a fundamental human characteristic; however, long-term social comparison may induce psychological stress and can lead to depression and anxiety. Recent...     

The role of consolidation for perceptual learning in temporal discrimination within and across modalities

Training people on temporal discrimination can substantially improve performance in the trained modality but also in untrained modalities. A pretest–training–posttest design was used to investigate whether consolidation plays a crucial role for training effects within the trained modality and its transfer to another modality. In the pretest, both auditory and visual discrimination performance was assessed. In the training phase, participants performed only the auditory task. After a consolidation interval of either 5 min or 24 h, participants were again tested in both the auditory and visual tasks. Irrespective of the consolidation interval, performance improved from the pretest to the posttest in both modalities. Most importantly, the training effect for the trained auditory modality was independent of the consolidation interval whereas the transfer effect to the visual modality was larger after 24 h than after 5 min. This finding shows that transfer effects benefit from extended consolidation.     

Effects of lipopolysaccharide on consolidation of partial learning in the Y-maze

Research on consolidation of long-term memory suggests that acute immune system activation induced by endotoxin lipopolysaccharide (LPS) may disrupt consolidation of newly acquired learning. Adult male Sprague-Dawley rats were trained to perform a simple Y-maze task and were immediately afterwards administered LPS (15 μg/kg) or saline. After a seven-day interval, subjects were returned to the Y-maze and were retrained to criterion. It was found that subjects treated with saline required significantly fewer trials to relearn the task relative to the LPS group and a no-partial-learning control group, which themselves did not differ. These results are most readily explained in terms of a disruptive effect of acute immune system activation on consolidation of newly induced acquired memories.     

Correction to: The effect of signaling in dependence on the extraneous cognitive load in learning environments

Cognitive Processing -     

From task characteristics to learning: A systematic review

Wielenga‐Meijer, E. G. A., Taris, T. W., Kompier, M. A. J. & Wigboldus, D. H. J. (2010). From task characteristics to learning: A systematic review. Scandinavian Journal of Psychology, 51, 363–375. Although many theoretical approaches propose that job characteristics affect employee learning, the question is why and how job characteristics influence learning. The present study reviews the evidence on the relationships among learning antecedents (i.e., job characteristics: demands, variety, autonomy and feedback), learning processes (including motivational, meta‐cognitive, cognitive and behavioral processes) and learning consequences. Building on an integrative heuristic model, we quantitatively reviewed 85 studies published between 1969 and 2005. Our analyses revealed strong evidence for a positive relation between job demands and autonomy on the one hand and motivational and meta‐cognitive learning processes on the other. Furthermore, these learning processes were positively related to learning consequences.