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PubMed2006

RISC-y Memories.

Local protein synthesis in the synapse is required for synaptic plasticity and has been implicated in learning and memory. However, direct evidence that behavioral training induces local protein synthesis has been lacking. In this issue of Cell, Ashraf et al. (2006) observe persistent local protein synthesis in the antennal lobe synapses of the fruit fly following olfactory-avoidance learning. This protein synthesis is regulated by the RNA-induced silencing complex (RISC).

Animals↗
PubMedDate not supplied

[Role of neuroexcitatory amino acids in memory processes. Study with gamma-L-glutamyl-L-aspartic acid].

Convergent data demonstrate that excitatory amino acid systems (glutamate and aspartate) participate in synaptic plasticity of the central nervous system. Their action is mediated by at least three subclasses of receptors which have been characterized on the basis of their selective affinity to N-methyl-D-aspartate (NMDA), quisqualate and kainate. NMDA receptors appear to be directly involved in the induction of long-term potentiation (LTP) at the hippocampal level, and quisqualate/kainate receptors in the expression of LTP. This suggests that excitatory amino acid systems may have an important role in learning and memory. However, how these systems interfere with memory processes remains largely unknown. We have isolated a pseudopeptide, gamma-L-glutamyl-L-aspartate (gamma-LGLA) (Ungerer et al., 1988), which has the pharmacological properties of a competitive antagonist at NMDA receptors as evidenced by biochemical studies and by the fact that gamma-LGLA selectively blocks the clonico-tonic seizures induced by NMDA, while having no significant action against seizures induced by kainate or quisqualate. Elsewhere, gamma-LGLA is devoid of toxicity at the doses used. Behavioral effects of gamma-LGLA were first studied in a Y-maze avoidance learning task. Animals had to leave the start alley within 5 sec. (temporal component) and to choose the left alley of the maze (spatial component) to avoid footshock. They underwent one trial every minute and were trained to a criterion of 7 correct out of 8 consecutive trials. Retention was tested either 1 h, 3 h, 6h, 24 h, 7 days or 21 days after acquisition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Enhanced maze performance and reduced oxidative stress by combined extracts of zingiber officinale and ginkgo biloba in the aged rat.

Here we assessed the effects of i.g. administration of Zingicomb (ZC), a mixture of zingiber officinale and ginkgo biloba extracts, on learning and memory, and on indicators of oxidative stress in aged rats. Effects of ZC (1 and 10 mg/kg) were investigated in 22-24 months old Wistar rats using the Morris water maze, in which they show deficient performance as compared to 3 months old rats in the undrugged state (days 1 and 2). Treatment was administered on days 3 and 4 of training, then over 7 days with training discontinued, and again on days 5 and 6 when training was resumed. Thereafter chronic treatment was maintained over 5 months. 1 mg/kg ZC improved escape learning in the water maze. The two capital indicators of oxidative stress in brain homogenates, the amount of oxidized proteins (assessed as carbonyl group containing proteins) and lipid peroxidation, were significantly reduced in ZC treated animals. Thus, ZC, which had previously been shown to improve inhibitory avoidance learning and to have anxiolytic properties in adult animals, might also facilitate spatial learning in aged animals, and reduces indices of oxidative stress in brain tissue after chronic treatment.

Aging↗
PubMed2004

Scopolamine given pre-Trial 1 prevents the one-trial tolerance phenomenon in the elevated plus-maze Trial 2.

A learned avoidance response has been one of the hypotheses proposed to explain the 'one-trial tolerance' (OTT) phenomenon, which represents a drug's loss of anxiolytic-like effect in the elevated plus-maze (EPM) test in experienced rodents. Based on these facts, if some kind of learning occurs throughout Trial 1, then an impairment of its acquisition would maintain the drug's anxiolytic-like effect on Trial 2. Using male Wistar rats, the present study examined whether scopolamine (SCO; 0.5-1.5 mg/kg), a drug that impairs learning acquisition, given 30 min prior to Trial 1, actually prevents the OTT phenomenon to either the midazolam (MDZ; 0.5 mg/kg) or the memantine (MEM; 8.0 mg/kg) anxiolytic-like effect on the EPM Trial 2 (48 h later). According to the results, both MDZ and MEM increased open-arm exploration (indicating anxiolysis) on Trial 2 only in rats that had been treated previously with 1.5 mg/kg SCO. These results were observed in the absence of change in general exploratory activity. The present findings suggest that SCO impaired the acquisition of the behavioral strategy to cope with the subsequent EPM exposure that supposedly underlies the OTT phenomenon, thereby revealing the anxiolytic-like effects of MDZ and MEM on Trial 2.

Adaptation, Psychological↗
PubMed1996

Effect of prenatal undernutrition and phenobarbitone administration on discrimination learning and passive avoidance behaviour in rats.

Effects of prenatal undernutrition and phenobarbitone administration, individually and conjointly, was assessed on learning acquisition and subsequent retention of a black/white discrimination task and passive avoidance behaviour in rats. Undernutrition of the dams was induced by restricting food intake to half, throughout the period of gestation, whereas phenobarbitone sodium (2.5 mg/kg, ip) treatment was given from day 13 to 20 of gestation, this being the critical period for neural development in rats. The pups were subjected to brightness discrimination learning, retention of the learning acquisition in a single unit black/white T-maze and passive avoidance behaviour test at 8-9 weeks of age. The results indicate that prenatal undernutrition induces significant discrimination learning and retention deficits in the offsprings. Prenatal phenobarbitone treatment also caused significant learning acquisition and retention deficits in the discrimination test. Phenobarbitone augmented the learning and retention deficits induced by undernutrition. However, both prenatal undernutrition and phenobarbitone treatments did not affect the retention of the learned passive avoidance. The results indicate that the prenatal interference in the form of undernourishment and anticonvulsant barbiturates, may induce functional deficits resulting in perturbed cognition in the offsprings.

Animals↗
PubMed1996

Spatial learning deficit in mice expressing human 751-amino acid beta-amyloid precursor protein.

Cognitive and other behavioural characteristics of 3-month-old heterozygous male transgenic mice expressing the 751-amino acid isoform of human amyloid precursor protein (hAPP751) under the control of a neurone-specific enolase promoter, were compared with those of age-matched non-transgenic control males. No difference was found between hAPP751 transgenics and non-transgenic controls in passive avoidance learning, or in motor coordination. Significantly decreased measures were found in the open field test and in cage activity indicative of general hypoactivity in hAPP751 transgenics. In water maze training, hAPP751 males required significantly longer to locate the hidden platform. This was not due to decreased swimming velocity in hAPP751 mice, but rather to increased path lengths. This suggests a purely spatial learning deficit in hAPP751 males even though their performance during a final spatial test, the probe trail that followed water maze training, was indistinguishable from that of controls. Decreased activity and impaired spatial learning were also reported in an independent study of hAPP751-expressing transgenics showing beta-amyloid immunoreactive deposits and altered tau protein. Since such histopathological alterations were not found in the transgenic model analysed in this study, our results indicate that beta-amyloid deposition is not required for the development of behavioural and/or cognitive deficits in hAPP751 transgenic mice.

Amyloid beta-Protein Precursor↗
PubMed1997

Dual role of 5-HT in defense and anxiety.

Pharmacological results obtained in animals tested in approach/avoidance conflict situations have led to the suggestion that 5-HT enhances anxiety by acting on forebrain structures. In contrast, results with intracerebral drug injection associated with aversive electrical brain stimulation indicate that 5-HT inhibits aversion in the dorsal periaqueductal gray (DPAG). To reconcile this evidence, it has been suggested that 5-HT may enhance conditioned fear in the amygdala while inhibiting innate fear in the DPAG. To test this hypothesis, we used three drug treatments known to increase the release of 5-HT from terminals of the dorsal raphe nucleus (DR): (1) intra-DR microinjection of the benzodiazepine inverse agonist FG 7142, (2) intra-DR microinjection of the excitatory amino acid kainic acid and (3) intraperitoneal injection of the 5-HT releaser and uptake blocker D-fenfluramine. All drug treatments enhanced inhibitory avoidance (learned fear) in the elevated T-maze, a new animal model of anxiety. Intra-raphe kainate and D-fenfluramine also decreased one-way escape (innate fear) in the T-maze. In contrast, reduction of 5-HT release by intra-DR injection of 8-OH-DPAT impaired inhibitory avoidance without affecting one-way escape. Overall, these results agree with the above hypothesis. Clinical implications are discussed, especially with regard to panic disorder.

Aggression↗
PubMed2006

Sex- and APOE isoform-dependent effects of radiation on cognitive function.

Clinical irradiation of the brain induces hippocampus-dependent cognitive impairments in some but not all individuals, suggesting the involvement of genetic risk factors. Deficiency of apolipoprotein E (APOE), which is important for the metabolism and redistribution of lipoproteins and cholesterol, increases behavioral impairments after irradiation, supporting a protective role for APOE against radiation-induced cognitive injury. Compared to APOE3, APOE4 increases while APOE2 decreases the risk of developing age-related cognitive decline and Alzheimer's disease, particularly in women. To determine the potential effects of APOE isoform and sex on radiation-induced cognitive impairments, we irradiated 2-month-old male and female APOE2, APOE3 and APOE4 mice and assessed their cognitive performance 3 months later. When hippocampus-dependent spatial learning and memory were assessed in the water maze, sham-irradiated female APOE2, APOE3 and APOE4 and irradiated female APOE2 mice showed spatial memory retention, but irradiated female APOE3 and APOE4 mice did not. Compared to sham-irradiated female APOE4 mice, irradiated female APOE4 mice also required more trials to reach criterion in the hippocampus-dependent passive avoidance test. Radiation had no effects on water maze or passive avoidance learning and memory of male APOE2, APOE3 or APOE4 mice, indicating that the effects of radiation on cognitive performance are dependent on sex- and APOE isoform.

Animals↗
PubMed2005

The role of plant secondary metabolites in mammalian herbivory: ecological perspectives.

Plant secondary metabolites (PSM) have many ecological functions, but have long been considered as defences against pathogens or herbivores (vertebrate or invertebrate), reducing the likelihood and extent of attack. However, mammalian herbivores ingest many foods containing PSM and use both behavioural methods and physiological strategies to limit their negative effects. Most physiological counter-adaptations are inducible in response to ingested PSM, providing efficient protection against toxic effects. Possible positive effects of PSM include antioxidant and anthelminthic properties and complex formation between protein and condensed tannins that protects dietary protein from degradation by the symbiotic microflora of foregut fermenters, increasing its utilisation by the animal. This protein effect is probably only beneficial to animals under a narrow range of nutrient-rich conditions found mainly in agricultural systems. There are many examples of PSM causing food avoidance or reducing food intake, but there is as yet relatively little evidence for positive selection of them by herbivores. Although the feedback mechanisms relating the post-ingestive consequences of PSM to subsequent foraging behaviour are beginning to be understood, knowledge of the integration of behavioural and physiological strategies for regulating the effects of PSM is relatively poor. The opportunities for learned avoidance of PSM may be restricted in animals with complex diets that cannot associate a particular feedback signal with a given food type. A greater emphasis on the study of subclinical effects of PSM rather than acute effects, on pharmaco-kinetic studies in relation to behavioural studies and on the use of realistic experimental models is advocated.

Animal Diseases↗
PubMedDate not supplied

Metabotropic glutamate receptors (mGluRs) are involved in early phase of memory formation: possible role of modulation of glutamate release.

Metabotropic glutamate receptors (mGluRs) groups I and II are involved in the cellular processes of long-term potentiation (LTP) and learning and memory formation. I.c.v. injection of the mGluRs agonist 1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) can impair memory formation in some types of learning task. The role of mGluRs in neurotransmitters release and production of second messengers has been suggested. The aim of the present study was to determine the effect of i.c.v. administration of the new potent mGluRs agonist ABHxD-I and compare its effect with that of ACPD. We studied the effect of both agonists on acquisition and memory for a one-trial passive avoidance learning task in day-old chicks and on the training related glutamate (Glu) release. ACPD or ABHxD-I (50 nmole per chick, i.c.v. injection) were administered at different times before or after training and chicks were tested at various times after training. Chicks injected with ABHxD-I 30 min before training showed amnesia when tested 30 min or 3h after training. The amnestic effect of ACPD was significant only 30 min after training. Glu release evoked by 70 mM KCl was measured in slices prepared from the IMHV of chick brain isolated from animals injected with either ACPD or ABHxD-I 30 min before training and tested 30 min after training. Glu concentration was measured using HPLC. Both ACPD and ABHxD-I significantly increased Glu release in slices isolated from untrained chicks (30 and 48% compare to control, respectively, P<0.05). Training itself increased Glu release (41% compared to control, P<0.01) and no additional effect of either ACPD or ABHxD-I was observed. These results suggest that mGluRs groups I and II are involved in the early stages of memory formation and that application of either of the studied mGluRs agonists may interfere with that process. The amnestic effect of ABHxD-I seems to be stronger and longer lasting. Although the mechanism of this effect still remains unclear, our results suggest that disregulation of Glu release by mGluR agonists may participate in this process.

Animals↗
PubMed2005

Deficient behavioral inhibition and anomalous selective attention in a community sample of adolescents with psychopathic traits and low-anxiety traits.

Socialization is the important process by which individuals learn and then effectively apply the rules of appropriate societal behavior. Response modulation is a psychobiological process theorized to aid in socialization by allowing individuals to utilize contextual information to modify ongoing behavior appropriately. Using Hare's (1991) Psychopathy Checklist and the Welsh (1956) anxiety scale, researchers have identified a relatively specific form of a response modulation deficit in low-anxious, Caucasian psychopaths. Preliminary evidence suggests that the Antisocial Process Screening Device (APSD; Frick & Hare, 2001) may be used to identify children with a similar vulnerability. Using a representative community sample of 308 16-year-olds from the Child Development Project (Dodge, Bates, & Pettit, 1990), we tested and corroborated the hypotheses that participants with relatively low anxiety and high APSD scores would display poorer passive avoidance learning and less interference on a spatially separated, picture-word Stroop task than controls. Consistent with hypotheses, the expected group differences in picture-word Stroop interference were found with male and female participants, whereas predicted differences in passive avoidance were specific to male participants. To the extent that response modulation deficits contributing to poor socialization among psychopathic adult offenders also characterize a subgroup of adolescents with mild conduct problems, clarification of the developmental processes that moderate the expression of this vulnerability could inform early interventions.

Adolescent↗
PubMed1991

Early postnatal hyperthyroidism alters hippocampal circuitry and improves radial-maze learning in adult mice.

Inbred mice show strain-specific differences in the hippocampal mossy fiber projection. These differences are most pronounced in the portion of the projection that forms synaptic connections with the basal dendrites of the CA3 pyramidal neurons [intra- and infrapyramidal mossy fiber (IIP-MF) projection]. We have previously demonstrated that the extent of the IIP-MF subfield is positively correlated with the capacity to perform a spatial radial-maze task and that an experimentally induced enlargement of the IIP-MFs, by means of postnatal thyroxine treatment, predicted the ability of adult two-way avoidance learning. In the present study, we tested whether this treatment would also influence radial-maze performance. Forty-five male mouse pups from the inbred strain DBA/2 (chosen because of scanty IIP-MF projection and poor radial-maze learning) were divided into three groups that received daily injections of either 2 micrograms L-thyroxine, an alkaline vehicle solution, or physiological saline. Treatment lasted from postnatal days 0 to 11. At the age of 3 months, these animals were tested in an eight-arm radial maze. The extent of their IIP-MF projections was measured by means of planimetry on Timm-stained sections. Thyroxine-treated animals made significantly fewer errors and had larger IIP-MF projections as compared to both control groups. Within each group, the individual variability of the IIP-MF projection was significantly and positively correlated with performance. We conclude that experimentally modified IIP-MF projections mediate processes underlying spatial working memory. It would appear that the hippocampal circuitry alterations induced by postnatal hyperthyroidism can counteract a hereditary lack of talent, albeit only partially and in selected populations.

Animals↗
PubMed2004

Disruption of reconsolidation but not consolidation of auditory fear conditioning by noradrenergic blockade in the amygdala.

Consolidation is a process through which labile memories are made persistent [Science 287 (2000) 248]; [Annu Rev Psychol 55 (2004) 51]. When retrieved, a consolidated memory is rendered labile again and undergoes reconsolidation [Learn Mem 7 (2000) 73]; [Trends Neurosci 26 (2003) 65]). Reconsolidation thus offers the opportunity to manipulate memory after it is formed, and may therefore provide a means of treating intrusive memories associated with post-traumatic stress disorder (PTSD). Reconsolidation is most usually studied using protein synthesis inhibitors, which is not practical in humans. However, the beta adrenergic receptor antagonist propranolol impairs consolidation of declarative memory in humans [Science 287 (2000) 248]; [Nature 371 (1994) 702] and consolidation and reconsolidation of inhibitory avoidance learning in rats [Brain Res 368 (1986) 125]; [J Neurosci 19 (1999) 6623]. Here, we show that systemic or intra-amygdala infused propranolol blocks reconsolidation but not consolidation. If the effects on reconsolidation are verified in humans, the results would suggest the possibility that propranolol after memory retrieval might be an effective way of treatment of intrusive memories in PTSD. That the systemic effects of propranolol on reconsolidation are achieved via an action in the amygdala is especially important in light of the fact that PTSD involves alterations in the amygdala [Arch Gen Psychiatry 53 (1996) 380].

Acoustic Stimulation↗
PubMed2001

Functional blocking of integrin-associated protein impairs memory retention and decreases glutamate release from the hippocampus.

We have previously demonstrated that integrin-associated protein is involved in memory consolidation of one-way inhibitory avoidance learning in rats and mice. In the present study, we examined the effects of functional blocking of integrin-associated protein on memory retention, long-term potentiation and glutamate release in mice as well as on cell attachment to extracellular matrix protein in primary cultures. The results indicated that integrin-associated protein monoclonal antibody miap301, when directly injected into the dentate gyrus of the hippocampus at moderate doses, significantly impairs memory retention in mice in the same one-way inhibitory avoidance task and decreases the amplitude of tetanic stimulation-induced long-term potentiation in dentate gyrus neurons. At a dose that effectively impairs both memory retention and long-term potentiation, integrin-associated protein monoclonal antibody also significantly blocks potassium chloride-induced glutamate release from the hippocampus in vivo. Results from western blot confirmed the presence of integrin-associated protein at the synaptic area. Cell adhesion experiments further revealed that integrin-associated protein monoclonal antibody markedly inhibits granular cell attachment to thrombospondin, the extracellular matrix protein known to bind integrin-associated protein, but not to collagen and laminin, the extracellular matrix proteins known to bind integrin. From these results we suggest that integrin-associated protein monoclonal antibody may impair synaptic plasticity and behavioral plasticity in mice through blockade of granular cell attachment to extracellular matrix protein and the subsequent signal transduction, and through inhibition of glutamate release from the hippocampus.

Animals↗
PubMed2000

Locomotor and learning deficits in adult rats exposed to monosodium-L-glutamate during early life.

Neonatal administration of neurotoxic doses of monosodium-L-glutamate (MSG) to rats causes neuronal necrosis of the hypothalamus along with behavioral abnormalities. In the present study the behavioral effects in rats treated with subneurotoxic doses of MSG (2 mg/g, p.o., for 10 days) at the weaned stage were investigated at day 90 post-dosing. The MSG-treated rats did not show significant changes in any of the components of spontaneous locomotor activity but, after apomorphine challenge, marked decreases in the distance travelled, ambulatory and stereotypic times, and the number of stereotypic movements with an increase in the resting time were observed. Significant decrease in the active avoidance learning performance was observed in the MSG-treated rats in the learning (acquisition) phase without any changes in the extinction and relearning phases. The results indicate that exposure to MSG in early life in rats could lead to subtle behavioral aberrations in late adulthood.

Age Factors↗