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At least 307 records · Page 17Linked to original sources

PubMed1994

Concomitant alterations of physiological and developmental plasticity in Drosophila CaM kinase II-inhibited synapses.

Ca2+/calmodulin-dependent protein kinase II (CaM kinase) has been implicated in neural plasticity that underlies learning and memory processes. Transformed strains of Drosophila, ala1 and ala2, expressing a specific inhibitor of CaM kinase are known to be impaired in an associative conditioning behavioral paradigm. We found that these transformants had altered short-term plasticity in synaptic transmission along with abnormal nerve terminal sprouting and directionality of outgrowth. These results represent an interesting parallel with the activity-dependent regulation of synaptic physiology and morphology by the cAMP cascade in Aplysia and Drosophila. In contrast to the learning mutants dunce and rutabaga, which are defective in the cAMP cascade, inhibition of CaM kinase in ala transformants caused increased sprouting at larval neuromuscular junctions near the nerve entry point, rather than altering the higher order branch segments. In addition, synaptic facilitation and potentiation were altered in a manner different from that observed in the cAMP mutants. Furthermore, synaptic currents in ala transformants were characterized by greater variability, suggesting an important role of CaM kinase in the stability of transmission.

Animals↗

PubMed2005

Learning-stage dependent Fos expression in the rat brain during acquisition of an olfactory discrimination task.

By using Fos immunocytochemistry, we investigated the activation in olfactory-related areas at three stages (the first and fourth days of conditioning and complete acquisition) of an olfactory discrimination learning task. The trained rats (T) had to associate one odour of a pair with water-reward within a four-arm maze whereas pseudo-trained (P) rats were only submitted to the olfactory cues without any reinforcement. In the piriform cortex, both T and P rats exhibited a higher immunoreactivity on the first day, which seemed to indicate a novelty-related Fos expression in this area, but whatever the learning-stage, no significant difference in Fos expression between T and P rats was observed. In hippocampus, Fos expression was significantly different between T and P rats in CA1 and CA3 on the first and fourth days respectively. Thus we showed a differential activation of CA1 and CA3 subfields which might support a possible functional heterogeneity. In the orbitofrontal cortex, Fos immunoreactivity was significantly higher in T rats compared to P rats when mastery of the discrimination task was complete. In contrast, no learning-related Fos expression was found in infralimbic and prelimbic cortices. The present data suggest an early implication of the hippocampal formation and a later involvement of neocortical areas throughout different stages of a progressively acquired olfactory learning task.

Analysis of Variance↗

PubMed2005

Medial septal galanin and acetylcholine: influence on hippocampal acetylcholine and spatial learning.

Neurochemical and behavioral studies in the rat have provided evidence for the view that galanin impairs learning via an inhibitory modulation of cholinergic neurons in the septohippocampal projection, believed to be important for learning and memory. To test this hypothesis, galanin was microinjected via a unilateral chronic cannula located in MS/dBB of rats. Infusion of galanin in the MS/dBB, which contains a high number of 125I-galanin binding sites, did not impair spatial acquisition or memory. On the contrary, spatial acquisition tended to be facilitated by 1 and 3 nmoles of galanin, while the 0.3 nmol dose had no effect. Intraseptal injections of scopolamine (10 microg/rat), a non-specific muscarinic antagonist, also failed to alter learning performance. In contrast, co-injections of galanin (3 nmol) and scopolamine (10 microg) resulted in a marked impairment of spatial acquisition. The effect of intraseptal galanin on basal acetylcholine release in the ventral hippocampus was examined by in vivo microdialysis and high-performance liquid chromatography. Both galanin (3 nmol/rat) and scopolamine (10 microg/rat) infused into the MS/dBB increased basal acetylcholine release in the ventral hippocampus. The combined injections of galanin and scopolamine resulted in an excessive increase in acetylcholine release. These results indicate, that galanin activates septohippocampal cholinergic neurons, suggesting that septal galanin may have a facilitatory role in spatial learning. Moreover, the level of muscarinic activity within the septal area appears to be critical for the effects of galanin on cognitive functions, since the combination of galanin and scopolamine produced a marked impairment in spatial learning, despite a marked increase in hippocampal acetylcholine release. In summary, a limited range of cholinergic muscarinic transmission may contribute to optimal hippocampal function, a finding that has important implications for therapeutic approaches in the treatment of disorders of memory function.

Acetylcholine↗

PubMed1995

Age and gender differences in the effectiveness of map-like learning aids in memory for routes.

Young (ages 25-40 yrs) and older (ages 60-75 yrs) adults viewed a series of slides depicting a route through a neighborhood and were tested on their ability to remember the route. Subjects either received no learning aid, a sketch of the route labeled as a "map," or the same aid labeled a "diagram." Aids either did or did not include route landmarks. Relative to younger men, older men's performance was significantly poorer only when they had no learning aid. In contrast, age differences for women were obtained only when the aid had been labeled a "map." The presence of landmarks eliminated age-related decrements in scene memory for men but increased them for women. In addition, results were consistent with the hypothesis that memory for large-scale environments is composed of "layout" (i.e., configural) and "scene" components.

Adult↗

PubMed2004

Investigating learning deficits associated with dyslexia.

An artificial grammar learning task was used to define two learning tasks of identical complexity at the symbolic level, but which differed in terms of stimulus format. The stimuli in one learning task were created so as to encourage participants to perceive each stimulus as a whole, with less emphasis on the stimulus constituent elements (the 'embedded' stimuli), while in the second task the constituent elements of each stimulus were emphasized by presenting them serially (the 'sequences' stimuli). Using a between participants design, dyslexic participants performed equally well in the two versions of the learning task. By contrast, non-dyslexic participants performed as well as dyslexic ones with the embedded stimuli but were impaired in the sequences stimuli. This finding was interpreted as showing that dyslexic participants were less able, compared to controls, to process individual stimulus elements of both the sequences and the embedded stimuli, consistently with recent work associating dyslexia with problems in attention focusing and shifting.

Adolescent↗

PubMed1990

Transplantation of peripheral cholinergic neurons into Alzheimer model rat brain.

The effect of transplantation of peripheral cholinergic neurons was examined in rats with a lesion of the nucleus basalis Meynert (NBM). The rats with an NBM lesion showed abnormal increase of spontaneous activity, disturbance of memory retention, and disturbance of learning acquisition. In contrast, the rats which had received transplantation of cholinergic neurons into the cerebral cortex displayed amelioration of abnormal behavior produced by the destruction of the NBM. Morphological study (acetylcholinesterase) clearly showed survival of many transplanted cholinergic cells. The present study suggests that autotransplantation of peripheral cholinergic cells may be a possible therapy for Alzheimer's disease.

Acetylcholinesterase↗

PubMed2004

Amino acid neurotransmitter release and learning: a study of visual imprinting.

The intermediate and medial part of the hyperstriatum ventrale (IMHV) is an area of the domestic chick forebrain that stores information acquired through the learning process of imprinting. The effects of visual imprinting on the release of the amino acids aspartate, arginine, citrulline, gamma-aminobutyric acid (GABA), glutamate, glycine and taurine from the left and right IMHVs in vitro were measured at 3.5, 10 and 24 h after training. Chicks were exposed to an imprinting stimulus for 1 h, their preferences measured 10 min afterward and a preference score calculated as a measure of the strength of learning. Potassium stimulation was used to evoke amino acid release from the IMHVs of trained and untrained chicks in the presence and absence of extracellular Ca2+. Ca2+-dependent, K+-evoked release of glutamate was significantly (34.4%) higher in trained than in untrained chicks. This effect was not influenced by time after training or by side (left or right IMHV). Training influenced the evoked release of GABA and taurine from the left IMHV at both 3.5 and 10 h. The training effects at the two times were statistically homogeneous so data (< or = 10 h group) were combined for each amino acid respectively. For this < or = 10 h group, evoked release increased significantly with preference score. In contrast, for the 24 h group, evoked release of GABA and taurine was not significantly correlated with preference score. There were no significant correlations between preference score and GABA or taurine release in the right IMHV at any time, nor in the absence of extracellular calcium. No significant effects of training condition, time or side were observed for any other amino acid in the study. The present findings suggest that soon after chicks have been exposed to an imprinting stimulus glutamatergic excitatory transmission in IMHV is enhanced, and remains enhanced for at least 24 h. In contrast, the learning-related elevations in taurine and GABA release are not sustained over this period. The change in GABA release may reflect a transient increase in inhibitory transmission in the left IMHV.

Amino Acids↗

PubMed2006

Transgenic inhibition of neuronal protein kinase A activity facilitates fear extinction.

Much is known about the neurobiology of memory storage for learned fear. In contrast, the molecular mechanisms underlying extinction of fear memory are just beginning to be delineated. Here, we investigate the role of protein kinase A (PKA) in extinction of memory for contextual fear by using conventional and temporally regulated transgenic approaches that allow us to inhibit PKA activity in neurons within brain regions thought to be involved in extinction. Strikingly, reduction of PKA activity facilitated the development of extinction, without interfering with storage of the original fear memory. Moreover, inhibition of PKA facilitated extinction of both recent and remote contextual fear memories. The finding that PKA, which is required for the acquisition of fear memory, is a constraint for extinction provides the first genetic support for the idea that fear extinction is itself a genuine learning process with its own specific molecular requirements, rather than simply the erasure of a previously learned process. Further, these experiments represent the first genetic evidence that protein kinases may be constraints for the extinction of fear.

Animals↗

PubMed2004

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↗

PubMed1995

Relationships between lead-induced learning impairments and changes in dopaminergic, cholinergic, and glutamatergic neurotransmitter system functions.

Behavioral consequences of low-level lead (Pb) exposure include impairments in learning processes and in Fixed-Interval schedule-controlled operant behavior. Although the neurobiological bases of these effects remain undetermined, current evidence suggests that inhibitory effects of Pb on the NMDA receptor complex may play a preferential role in the learning deficits. In contrast, alterations in dopaminergic systems, consistent with a decrease in dopamine availability, appear to be related to the changes in Fixed-Interval performance. Hypocholinergic function has also been described, but its relationship to the behavioral changes is not yet known. Explication of these relationships will require more efforts involving direct rather than correlative methods. The answers are critical for understanding risks associated with exposure and for the development of behavioral or chemical therapeutic strategies for dealing with lead neurotoxicity.

Animals↗

PubMed2006

Functional magnetic resonance imaging study of regional brain activation during implicit sequence learning in obsessive-compulsive disorder.

BACKGROUND: Corticostriatal circuitry has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). The serial reaction time (SRT) task, a paradigm that tests implicit sequence learning, has been used with imaging to probe striatal function. Initial studies have indicated that OCD patients exhibit deficient striatal activation and aberrant hippocampal recruitment compared with healthy control (HC) subjects. Here, we used the SRT and functional magnetic resonance imaging (fMRI) to replicate prior results in a larger sample and to test for relationships between regional activation and OCD symptom dimensions. METHODS: Using SPM99, fMRI-SRT data from 12 OCD and 12 matched HC subjects were analyzed. Symptom dimensions followed a four-factor model scored on a 0- to 10-point scale. RESULTS: For the implicit learning versus random contrast, group by condition interactions revealed aberrant recruitment within the hippocampus as well as orbitofrontal cortex (OCD > HC) but no striatal group differences. However, an inverse correlation was found between striatal activation and specific symptom factors. CONCLUSIONS: These results replicate previous smaller studies showing aberrant hippocampal recruitment in OCD during SRT performance. Although findings of deficient striatal activation in OCD were not replicated, correlation results suggest that this inconsistency may be attributable to differences among OCD symptom dimensions.

Adult↗

PubMed1993

A model for conceptual processing of naturalistic scenes.

Are there fundamental differences in the way in which a list of pictures and a list of words are processed? We report three experiments that examine serial position effects for rapidly-presented naturalistic scenes. The experiments provide a basis for comparison with the U-shaped serial position curve and list-length effect which typically result from verbal learning experiments. In contrast to the U-shaped verbal serial position function, our results show a flat function at the beginning serial positions and a recency effect which is small and limited to the last serial position. There is a set-size effect. Results suggest that the processing leading to a memory representation for visual stimuli such as pictures and linguistic stimuli such as words is qualitatively dissimilar. The findings can be accounted for by a serial processing model whose main parameter is the probability that the subject will switch attention from one picture to the next.

Attention↗

PubMed1999

Anhedonic and anxiogenic effects of cytokine exposure.

Systemic interleukin IL-1 beta, TNF alpha, and IL-2 profoundly influenced central monoamine activity, as well as behavioral outputs. The effects of the various cytokines were clearly distinguishable from one another, although synergistic effects were detected between several of these cytokines and between the actions of cytokines and stressors. Acutely applied IL-2 appeared to affect reward processes, but did not affect anxiety. When chronically administered, this cytokine markedly influenced working memory in a spatial learning test. In contrast to IL-2, both IL-1 beta and TNF alpha appeared to provoke an anxiogenic action, and provoked clear signs of illness. While these cytokines induced anorexia, they did not appear to affect reward processes. IL-1 beta and TNF alpha were found to act synergistically, and the TNF alpha provoked a sensitization with respect to the action of subsequent TNF alpha treatment. The findings indicated that cytokine treatments profoundly influence extrahypothalamic neurochemical functioning and may thus impact on behavioral outputs. Analyses of the behavioral and neurochemical changes elicited by cytokines, and particularly TNF alpha, need to consider not only the immediate impact of such treatments, but also the proactive effects that may be engendered.

Animals↗

PubMed1986

An assessment of verbal recall, recognition and fluency abilities in patients with Huntington's disease.

Two investigations concerned with the memory deficits of patients with Huntington's Disease (HD) were performed. In the first experiment, early and advanced HD patients showed superior recognition memory than did alcoholic Korsakoff patients on modified recall and recognition forms of the Rey Auditory Verbal Learning Test. In contrast, on a letter fluency test (FAS) requiring the patients to search their semantic memories, both HD groups produced fewer correct words and perseveration errors than did the alcoholic Korsakoff group. In the second experiment, HD patients and Korsakoff patients were compared in their and recognition of short passages. While the HD and Korsakoff patients were equally impaired on recall tests, the HD patients evidenced significantly better recognition memory than did the amnesic group. As on the fluency test, the prose of the Korsakoff patients was characterized by intrusion (i.e., perseverative) errors. The results of the two experiments indicate that HD and Korsakoff patients' memory deficits are related to deficiencies in retrieval and an increased sensitivity to proactive interference, respectively.

Alcohol Amnestic Disorder↗

PubMed1998

Memory impairments associated with hippocampal versus parahippocampal-gyrus atrophy: an MR volumetry study in Alzheimer's disease.

Delayed memory impairments and medial temporal-lobe atrophy are considered to be cardinal features of Alzheimer's disease (AD). The goal of the present magnetic resonance (MR) volumetry study was to investigate the relationship between both features. We determined MR-derived estimates of hippocampal and parahippocampal volume in a sample of 27 AD patients and in a group of 26 healthy control subjects (NCs) of comparable age and education. We examined the performance of the two groups on immediate and delayed recall trials of an auditory-verbal list-learning task (CVLT), a visual non-verbal memory task (Visual Reproduction of the WMS-R), and a screening procedure that provides an estimate of overall cognitive functioning (DRS). Volumes of the hippocampus and the parahippocampal gyrus were significantly smaller in AD patients than in NCs. AD patients were impaired in their overall level of cognitive functioning and showed memory deficits under immediate and delayed recall conditions. The association between medial temporal-lobe atrophy and cognitive impairments in AD was found to be highly specific: Hippocampal volume correlated positively with delayed but not immediate recall of the verbal auditory list learning task. In contrast, parahippocampal gyrus volume, specifically in the right hemisphere, was positively related to delayed but not immediate recall of the non-verbal visual memory task. In NCs, there was a trend towards a negative association between hippocampal volumes and delayed verbal recall. Our results suggest that hippocampal and parahippocampal gyrus atrophy in AD are related to distinct aspects of the patients' memory impairments. Our findings have implications for current discussions regarding contributions of the hippocampus and the parahippocampal gyrus to memory in the intact human brain.

Aged↗

PubMed1997

In times of change learners inherit the earth. The 1997 presidential address.

Neurosurgery, as traditionally practiced, is changing. Eric Hoffer observed, "In times of change learners inherit the earth; while the learned find themselves beautifully equipped to deal with a world that no longer exists." Historically, learners have possessed certain attributes. They anticipate rather than react to change. They become essential facilitators within their altered environment. They are effective advocates for principled behavior and ethical practices. They skillfully communicate the new and technically arcane with a common touch. Learners also understand the lessons of history. The potential of process technology, illustrated by Morton's 1846 application of already well-understood science, in essence, to transform the profession of surgery by making painless operations possible, is one example. Voluntary professional associations such as organized neurosurgery can also learn from the contrasting experiences of the Donner Party and the Utah Pioneers as they made their way down the same canyon of the Wasatch mountain range during the summers of 1846 and 1847, respectively. Group dynamics during those two episodes differed strikingly. It was the vanguard party of Utah Pioneers who exemplified the characters of learners. They acted with unity, common purpose, and careful preparation designed to benefit those who followed them. Years from now, how will the current individual and institutional behavior of neurosurgeons and their associations be judged? An interval assessment is suggested at the April, 2012 American Association of Neurological Surgeons Annual Scientific Meeting. From that perspective, will it be determined that the neurosurgical discipline acted presciently, as would those Hoffer describes as learners? Will neurosurgery be said to have understood and thereby profited from the lessons of history? These are pertinent questions. The answers, considered as a proposed progress report 15 short years from now, could accurately predict the scientific and professional position that neurological surgery will occupy in the future. Deserved long-term success based on the effective, far-sighted behavior exhibited by learners is my confident expectation.

Communication↗

PubMed1996

Impaired learning in mice with abnormal short-lived plasticity.

BACKGROUND: Many studies suggest that long term potentiation (LTP) has a role in learning and memory. In contrast, little is known about the function of short-lived plasticity (SLP). Modeling results suggested that SLP could be responsible for temporary memory storage, as in working memory, or that it may be involved in processing information regarding the timing of events. These models predict that abnormalities in SLP should lead to learning deficits. We tested this prediction in four lines of mutant mice with abnormal SLP, but apparently normal LTP-mice heterozygous for a alpha-calcium calmodulin kinase II mutation (alpha CaMKII +/-) have lower paired-pulse facilitation (PPF) and increased post-tetanic potentiation (PTP); mice lacking synapsin II (SyII-/-), and mice defective in both synapsin I and synapsin II (SyI/II-/-), show normal PPF but lower PTP; in contrast, mice just lacking synapsin I (SyI-/-) have increased PPF, but normal PTP. RESULTS: Our behavioral results demonstrate that alpha CaMKII +/-, SyII-/- and SyI/II-/- mutant mice, which have decreased PPF or PTP, have profound impairments in learning tasks. In contrast, behavioral analysis did not reveal learning deficits in SyI-/- mice, which have increased PPF. CONCLUSIONS: Our results are consistent with models that propose a role for SLP in learning, as mice with decreased PPF or PTP, in the absence of known LTP deficits, also show profound learning impairments. Importantly, analysis of the SyI-/- mutants demonstrated that an increase in PPF does not disrupt learning.

Animals↗

PubMed2000

Effects of selective perirhinal and postrhinal lesions on acquisition and retention of a visual discrimination task in rats.

The hippocampal region along with rhinal structures seems to support learning and memory in an important manner. Structures adjacent to the rhinal fissure in the rat have recently been suggested to be divided into the perirhinal and postrhinal cortices. Some effects of perirhinal lesions on cognitive processing are known, whereas effects of postrhinal lesions appear to be unknown. The purpose of the present study was to examine the relative effects of perirhinal and postrhinal lesions in a three-choice visual discrimination test. The results show that both types of lesions impaired acquisition of the task, but only perirhinal lesions impeded subsequent retention. Because the initial phase of acquisition was unaffected by both lesions, it is suggested that the deficits observed may be of mnemonic nature. The apparent differential involvement of the perirhinal cortex and postrhinal cortex in cognition may be associated with differences in anatomical connectivity among these structures.

Animals↗