Consolidation Of Memory Traces Research Articles

Detection of protein with anticonsolidation properties in the rat brain.

Isolation and identification of rat brain protein regulated by serotonin-modulated protein SMP-69 is described. Intracerebral administration of anti-SMP-69 antibodies activates cerebral cortex cell genome and increases the content of electropheretic fraction 28. Intracerebral administration of isolated and purified protein to rats disturbed memory consolidation. It is concluded that nerve cells have a molecular switch regulating consolidation of memory traces.

Genetic mechanisms of the involvement of SMP-69 protein in memory consolidation

Intracerebral administration of antibodies to SMP-69 protein to rats 24 h prior to passive avoidance conditioning impaired memory processes, while the administration 48 h after learning had no such effect. Activation of RNA and protein synthesis was observed 24 h after the administration. It is suggested that the impaired consolidation of memory traces is due to the synthesis of “anticonsolidation” proteins.

Are glutamate receptors specifically implicated in some forms of memory processes?

Convergent data indicate that certain substances that interact with N-methyl-D-aspartate (NMDA) receptors or metabotropic glutamate receptors (mGluRs) do not affect acquisition processes per se, or retrieval, but interfere specifically with the formation of memory traces. This action differs widely in its amplitude and time-course according to the learning task used. We showed that systemic injection of the competitive NMDA receptor antagonists, gamma-L-glutamyl-L-aspartate (gamma-LGLA) and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), or intracerebroventricular infusion of D-2-amino-5-phosphonovalerate (D-AP5), immediately following acquisition of a Y-maze avoidance learning task in mice, deeply impaired retention of the temporal component of the task (leaving the start alley within the first 5 s of a trial), which significantly improved in controls during the hours following acquisition. In contrast the same substances had no or only slight effects on retention of the discrimination component (choice of the correct alley), which did not improve over time in control animals. This retention deficit did not appear to be due to an action on acquisition, retrieval and/or forgetting processes, or to state-dependent effects. Moreover, gamma-LGLA, CPP or AP5, when administered immediately after partial acquisition of a food-reinforced bar-press task, suppressed the spontaneous improvement in post-training performance observed in control mice 24 h after the training session. (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG), an antagonist of mGluRs, also suppressed the post-training performance increment and its effects were antagonized by the co-administration of trans-ACPD, an agonist of mGluRs. Post-training improvement of performance over time is thought to reflect an active and dynamic process, leading to the organization of memory traces. According to this hypothesis, our results suggest that synaptic plasticity mediated by NMDA receptors and/or mGluRs activation is involved in mechanisms underlying long-term consolidation of memory traces.

Genetic aspects of the mechanisms of learning.

Published data demonstrating the direct involvement of the genome in processes associated with learning are presented. These processes include the intensification of protein and RNA synthesis during learning and induction of early gene expression during learning. The relationship between consolidation of memory traces and protein synthesis is discussed. Along with different types of memory needing induction of gene expression for consolidation, some types of long-term memory are independent of protein synthesis. The use of genetic methods for studying the mechanisms of learning and memory is discussed.

Retrograde Enhancement of Human Kinesthetic Memory by Alcohol: Consolidation or Protection against Interference?

Alcohol intake is known to impair memory in animals and humans. However, five studies reported that “medium” (0.05 ml/kg body weight) to “high” (1.0 ml/kg body weight) doses of alcohol improved memory when drunk immediately after initial learning of verbal or visual material. It was proposed that alcohol brought about this retroactive facilitation either through enhanced consolidation of memory traces or by protecting against retroactive interference. The present double blind study compared the performances of an alcohol and a placebo group on a kinesthetic memory task before alcohol or placebo intake and at retest 1 h after consumption. A second experiment was identical to the first except that all subjects carried out two trials on a T maze in the hour between testing and retesting. The alcohol group in the first experiment performed significantly better than the placebo group at retest (p< .05) but this was not the case in the second experiment. Alcohol therefore enhanced performance on the kinesthetic memory task in the first experiment but may not have protected against the moderate interference from the T maze in the second. The low levels of alcohol could have had a stimulant effect on trace consolidation, perhaps via raised blood glucose levels.

Engram activation reinstates the susceptibility of consolidated memory traces to retrograde amnesia by functional blockade of parabrachial nuclei

Previous studies have shown that in rats the acquisition of a step-through passive avoidance reaction (PAR) in the light-dark box apparatus is disrupted by tetrodotoxin (TTX) inactivation of the parabrachial nuclei (PBN) 24 but not 48 h after the acquisition trial. The present experiment shows that TTX induces retrograde amnesia even when applied to the PBN 48 h after PAR acquisition only if it is preceded by a 30-min confinement (extinction) or by a footshock (retraining) in the dark compartment. These stimuli, independently of their sign, induce quantitatively comparable TTX disrupting effects. This happens notwithstanding the fact that these stimuli are too weak to modify PAR under control conditions. This paradoxical finding suggests that engram vulnerability may not be a simple inverse function of its recency but that it may reflect a reactivation of the neural circuits involved in memory trace formation. Consolidated engrams become again vulnerable only when contextual cue stimuli are presented shortly before the application of the disrupting procedure.

Reversal of scopolamine-induced amnesia and alterations in energy metabolism by the nootropic piracetam: implications regarding identification of brain structures involved in consolidation of memory traces

Pretreatment with scopolamine, 3 mg/kg, prevented the acquisition of a passive avoidance task in rats. These amnesic effects of scopolamine could largely be treatment with 100 mg/kg of the nootropic drug piracetam. In order to identify the brain structures involved, the effects of these drugs on regional energy metabolism were measured throughout the brain, utilizing Sokoloff's 2-deoxyglucose autoradiographic procedures. Scopolamine, 3 mg/kg, reduced glucose utilization in several areas of the cerebral cortex. These effects were largest in the parietal and temporal cortices. Other areas affected included the sensorimotor and cingulate cortices, the ventral and lateral thalamus, and the dendritic neuropil of the CA 1, CA 2, and CA 3 regions of the hippocampus. The regional depressions in glucose metabolism observed following scopolamine treatment in the rat had some resemblance to depression in glucose metabolism reported for Alzheimer's disease patients in positron emission tomography studies. Piracetam, 100 mg/kg, did not alter the energy metabolism of any of the 41 brain regions examined. However, this dose of piracetam completely reversed the scopolamine-induced depressions in the hippocampus. Piracetam partially but significantly reversed the scopolamine effects in the the cingulate cortex. It is concluded that the data provide support for the hippocampal-cholinergic theory of memory as originally formulated by Meyers and Domino in 1964 and give insight into the mechanisms by which nootropics work.

Interaction between learning and paradoxical sleep in cats.

1. Learning sessions for the acquisition and extinction of alimentary conditioned responses do not significantly alter the structure of the wakefulness-sleep cycle during the post-conditioning period, and the percentage ratio of the different phases is preserved, without an augmentation of one of them. 2. Under the influence of learning sessions the number of awakenings for the deprivation of paradoxical sleep does not change, making it possible to reject the idea that learning has any appreciable influence on the formation of PS requirement. 3. PS deprivation brought about by non-emotional awakening after learning sessions does not delay the acquisition or extinction of alimentary conditioned responses. 4. The conclusion is drawn that paradoxical sleep has no specific role to play in memory trace consolidation during the formation of long-term memory.

Selective vulnerability of hippocampus and disturbances of memory storage after mild unilateral ischemia of gerbil brain.

The effect of selective injury of hippocampal neurons on the consolidation of memory traces was studied in gerbils (meriones unguiculatus) after production of mild cerebral ischemia. The right carotid artery was permanently ligated, and animals without gross neurological deficits ("symptom-negative" gerbils) were selected. Eight days and eight weeks after vascular ligation, cell counts of hippocampal neurons were carried out and correlated with regional blood flow and the acquisition of operant behaviour. Eight days after carotid artery occlusion, learning behaviour was significantly impaired although the number of hippocampal neurons had not changed and blood flow had even increased above normal. After eight weeks, learning behaviour and blood flow were normal but now a significant loss of pyramidal neurons was present in the CA1 and CA2 sectors of the hippocampus. Our observations demonstrate that it is possible to detect subtle functional disturbances by appropriate behavioural investigation before manifestation of selective injury of the hippocampus. Recovery of integrative function, despite persistent cellular damage, provides further evidence for central nervous plasticity.

Does paradoxical sleep deprivation disturb memory trace consolidation?

The effect of water tank PSD on memory in the passive avoidance test as well as on open field behavior was studied in rats. The effect of combining water tank PSD with a period of normal sleep-wakefulness cycle or with PSD by non-emotional awakening was investigated in a special series of experiments. It is concluded that PSD, even by the water tank procedure, does not disturb trace consolidation and formation of long-term memory in the passive avoidance test. However, a change in the correlation of motor-exploratory activity and fear reaction, due to the stressful situation intrinsic in the water tank PSD procedure, does not allow the animals to reach comparatively long temporal criteria in the passive avoidance test.

Changes in size and shape of synaptic connections after visual training: An ultrastructural approach of synaptic plasticity

The effect of visual training 30 on the synapses in the visual cortex of rabbits was quantitatively investigated. The number, the size and the fine structural organization of synaptic grids were analyzed in 0.5 μm E-PTA sections. The size of the pre- and postsynaptic terminals, the length of the apposition zones, the number of synaptic vesicles per terminal, the dimensions of the synaptic cleft and postsynaptic density and the frequency of mitochondria and spine apparatuses were studied in conventional OsO 4 sections. As compared to control animals, the synaptic population of visually trained rabbits exhibits 3 important changes: 1. (1) the number of complex grids has significantly increased; (perforated synapses according to refs. 6 and 24), 2. (2) the size of the synaptic grids has decreased. As is deduced from careful electron microscopic observations, this decrease in size is the result of a focalization of large grids. 3. (3) a significant increase in thickness of the postsynaptic density and a decrease in synaptic cleft is observed. The changes are most pronounced in deep layers (L IV and V) and are almost absent in superficial layers (L I). On account of recent insights into the mechanism of synaptic transmission and of the intrinsic relation between the fine structural components of the synaptic junction and the process of transmitter release, the observed changes are interpreted as an expression of enhanced synaptic efficacy. It is further postulated that modification of synaptic efficacy must be considered as an important factor in the adaptation of the nervous system to changing environmental conditions and for the consolidation of memory traces.

Investigations on the Retroactive Influence of Latent Visual Learning on Previously Formed Memory Traces in Fish1

Experiments with crucians (Carassius carassius L.) and goldfish (Carassius auratus L.) have shown that a consolidated memory trace of a simple visual pattern became disturbed by later seeing series of similar patterns (unrewarded), that is to say by latent learning. In a test in which the experimental group (es) had to choose between the originally learnt and the similar pattern, it did not prefer the former, whereas the control group (cs), which had only seen white walls of the aquarium, still preferred the originally learnt pattern. The same happened when es learnt a similar pattern by reward after the memory of the original pattern had been consolidated. In another set of experiments the negative influence of post-exposure could be demonstrated in facilitation of later learning the postexposed pattern as positive versus the originally learnt pattern, now negative. When es had seen a dissimilar wall-paper pattern then the memory of the primarily learnt pattern was not disturbed. A tentative explanation is based on the notion that two similar engrams have part of the neuronal network in common.

Firing rates and patterns of output and nonoutput cells in cortical areas 5 and 7 of cat during the sleep-waking cycle

The rate and patterns of spontaneous discharge in output cells and putative interneurons of cortical areas 5 and 7 were analyzed in the behaving cat during wakefulness (W), synchronized (S) sleep, and desynchronized (D) sleep, with (D+) and without (D−) rapid eye movements (REMs). Output cells were antidromically identified following stimulation of the thalamic and pontine nuclei. Interneurons were inferred from their thalamically elicited synaptic responses consisting of high-frequency spike barrages. Non-parametric (rank) statistics were used for tests of significance. A method derived from the Wilcoxon rank tests was developed to permit some statistical testing between interspike interval histogram patterns. Rate analysis showed that output cells discharge in all states of the sleep-waking cycle at significantly higher rates than interneurons. Corticothalamic and corticopontine cells decreased firing rates from W to S sleep and reached maximal rates in both (D+ and D−) substates of D sleep. In contrast, interneurons increased firing rates from W to S sleep and had their highest rates in D sleep, selectively occurring during REM epochs. In output cells, pattern differences between states consisted essentially of: (a) more short and long interspike intervals in S sleep compared to W, which indicates an increase in the burst-silence pattern in S sleep; (b) more short, but less long, intervals in D sleep, compared to both W and S sleep, which results from tonic excitation during D sleep and indicates that the firing pattern in D sleep is not an extreme type of S sleep. Compared to output cells, interneurons in all states had more short and long intervals and a significantly higher probability of spike bursts. The REM-related firing of interneurons may be related to recent investigations suggesting the consolidation of memory traces during D sleep.

Paradoxical sleep and memory storage processes

This paper advances the view that during the paradoxical sleep (PS) phase, the brain sets in motion a “chain-of-events” that is necessary for learning ability and that these events are an integral component of memory storage processes. The evidence supporting the position taken in this paper comes from experiments showing that: (1) PS deprivation (PSD), prior to training or immediately thereafter, impairs the formation of a permanent memory trace; (2) prolonged PSD following learning interferes with the state of a consolidated memory trace; (3) in the course of distributed learning, each learning session is followed by a brief augmentation of PS; (4) massed learning, in which registration of a learned response is incomplete, is followed by a protracted augmentation of PS; (5) pharmacological alterations of brain protein synthesis, cholinergic and catecholaminergic neurotransmitter activity are paralleled by the appearance or disappearance of PS periods, with concomitant changes in memory. The accumulated data suggest that the events occurring during the PS phase play an integral part in memory storage processes in two ways: (1) provide conditions which facilitate the conversion of a learned response into a stable long-term memory, and (2) actively maintain the stability of a consolidated memory trace.

Dream recall: Facts and perspectives

The author has reviewed some of the questions of dream recall. His main proposal is that dream research has to pay more attention to conditions necessary to consolidation of memory traces than has been done till now. Psychodynamics of nonrecall, such as repression, seem to play a role of secondary importance as compared with problems of memory consolidation.

Retrograde amnesia produced by electroconvulsive shock after reactivation of a consolidated memory trace: A replication

Rats showed retrogarde amnesia when electroconvulsive shock was administered 24 h after a fear conditioning trial when the shock was preceded by some of the specific conditioning cues but not others. This result replicates the findings of Misanin, Miller, & Lewis (1968) and suggests that ECS can act to produce retrograde amnesia by means other than disrupting memory consolidation.

Subjective estimation of the duration of time periods in night sleep.

DURING sleep, the brain continues to process information received in the waking state and rapid eye movement sleep (REMS) in particular seems usually to have a special role in the consolidation of memory traces and “programming” mechanisms in the brain1-5. We have attempted to elucidate the nature of the information processing activity of the brain during sleep and particularly during delta sleep by examining subjective impressions of the duration and quality of sleep after a wakening from sleep of different stages and cycles.

Some experiments concerning the effects of sleep on memory.

ABSTRACTA series of studies was conducted in an attempt to explore the effect of sleep on consolidation of memory traces. In each study, Ss were shown words shortly after each of several awakenings during the night. After the words were shown, the Ss were either permitted to return to sleep immediately (S treatment) or were kept awake for 5 min working on a psychomotor task (A treatment). Memory for the words was tested the following morning.Under the (S) treatment condition, retention was positively related to the time taken to return to sleep after the word was shown. It was possible to replicate previous findings that retention is better in the (A) than in the (S) treatment. However, this treatment effect was found only if the psychomotor task was conducted under testlike conditions and only if the Ss pronounced the words during the stimulus presentation. If the task was presented to the S as a game, or if pronunciation was delayed until after the presentation ended, merely keeping the S awake in the (A) treatment did not improve retention. The phenomena observed do not appear to be easily interpreted as an effect of sleep on memory.

Electroconvulsive shock effects on a reactivated memory trace: further examination.

Rats showed amnesia for conditioned fear training if given an electroconvulsive shock immediately after training. Retention was unimpaired, however, when the electroconvulsive shock treatment was given 1 day after training immediately after the presentation of the stimulus used in the fear conditioning training. These results support the view that electroconvulsive shock disrupts memory trace consolidation but does not disrupt a recently reactivated memory trace.

Reminiscence and Consolidation in a Gross Motor Task

It has been proposed by Eysenck (1965) that following massed practice conditions there is a period of consolidation of memory traces after S is no longer performing the learning task. An experiment was carried out attempting to interfere with the consolidation process. The effect of reading aloud' on reminiscence on a motor task was examined in 52 male students. Ss were given 3 learning periods of 5 min. of continuous practice; between learning periods, there was a 5-min. rest interval during which S was given either an experimental condition of reading or a control condition. It was found that the amount of reminiscence did not differ significantly under control and experimental conditions.