Puromycin effect on successive phases of memory storage

Mice injected bitemporally with puromycin 5 hours before training learned to escape or to avoid shock by choosing the correct limb of a Y-maze. When retested 15 minutes after training they had normal retention. In the ensuing 2(3/4) hours the animals injected with puromycin, unlike the controls, showed a progressive decrease of savings to less than 7 percent.     

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.     

Actinomycin D blocks formation of memory of shock-avoidance in goldfish

When 2 micrograms of antinomycin D was injected intracranially into goldfish immediately after a training session, the formation of long-term memory of a shock-avoidance was blocked. The results are discussed in relation to similar findings with acetoxycycloheximide and puromycin in the goldfish and with apparently conflicting results in the mouse.     

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

Rats had a memory loss of a fear response when they received an electroconvulsive shock 24 hours after the fear-conditioning trial and preceded by a brief presentation of the conditioned stimulus. No such loss occurred when the conditioned stimulus was not presented. The memory loss in animals given electroconvulsive shock 24 hours after conditioning was, furthermore, as great as that displayed in animals given electroconvulsive shock immediately after conditioning. This result throws doubt on the assertion that electroconvulsive shock exerts a selective amnesic effect on recently acquired memories and thus that electroconvulsive shock produces amnesia solely through interference with memory trace consolidation.     

Intracerebral saline: effect on memory of trained mice treated with puromycin

It was shown that puromycin administered to mice 1 or more days after maze-learning blocks expression of memory; the blockage can be removed by intracerebral injections of saline. We present evidence that intracerebral injections of saline are relatively ineffective in restoring memory when puromycin is administered either before or immediately after training; in these two situations puromycin appears to interfere with consolidation of memory.     

Retrograde amnesia: production of skseletal but not cardiac response gradient by electroconvulsive shock

Rats given a single electroconvulsive shock immediately after but not 60 seconds after an aversive conditioning trial exhibited behavioral retention deficits 24 hours later in a one-trial passive avoidance task. In contrast to these differential performance deficits, similar heart-rate changes, indicative of fear retention, were seen in punished animals irrespective of the time of delivery of the shock. These data suggest retention of a generalized fear to the training experience that was not revealed by the behavioral measure. The potential usefulness of concomitant behavioral and physiological response assessment in consolidation research is discussed.     

Retrograde Amnesia from Conditioned Competing Responses

If electroconvulsive shock is given immediately after a learning trial, retrograde amnesia for that response occurs. The usual interpretation of such amnesia states that a neural engram, after a learning trial, requires a certain amount of time to consolidate, and electroconvulsive shock interferes with this consolidation, producing amnesia. Four studies are summarized which indicate that convulsive shock serves as an unconditioned stimulus producing a convulsive response, that takes precedence over other behavior, and part of which becomes conditioned to stimuli in the learning situation. The convulsive response competes with, and replaces, the previous response, resulting in the appearance of amnesia.     

Extinction following intracranial reward: the effect of delay between acquisition and extinction

Rats trained to press a bar for intracranial reinforcement gave as many responses during extinction as did water-reinforced controls, when extinction came immediately after an acquisition session. However, the experimental animals gave fewer responses in extinction than water-reinforced animals when extinction was delayed for 1 hour after acquisition. The activity level of the experimental animals was high immediately after acquisition but declined markedly over the delay period, which suggests that resistance to extinction after intracranial reinforcement is primarily a function of activity level.     

Memory in mice analyzed with antibiotics. Antibiotics are useful to study stages of memory and to indicate molecular events which sustain memory

It is apparent that antibiotics are useful in differentiating different stages in the formation of memory. Puromycin gave the first indication that very early memory can be established and survive, for a short period at least, in spite of inhibition of protein synthesis (12). Injection of actinomycin D indicates that RNA synthesis is not essential during this early stage (13). The duration of this early period seems to vary with the inhibiting agent; with puromycin memory was notably degraded in less than an hour, but with actinomycin D or with acetoxycycloheximide it persisted for several hours or more. The fixation or consolidation of memory involves whatever processes give permanence to memory. These processes are disrupted when electroconvulsive shock is administered shortly after a learning experience, presumably because of the interference with organized patterns of neuronal electrical activity. Memory acquired in the presence of antibiotics appears to proceed to a stage beyond that based purely on electrical activity because the memory persists beyond the period usually reported as sensitive to electroconvulsive shock. Further work should show whether this stage is truly insensitive to electroconvulsive shock. Memory acquired in the presence of puromycin does not seem to achieve any durable consolidation. In contrast, memory acquired in the presence of or immediately before injection of acetoxycycloheximide does appear to initiate the later stages of consolidation, as permanent memory. reappears some days after the initial stages have become ineffective in controlling performance. Finally, puromycin has provided evidence of the enlarged area of the neocortex which participates as memory matures. Puromycin also indicates the time required for this maturation process. Since antibiotics have also been useful in studying learning and memory in goldfish (14), this approach seems to have general applicability in defining various stages in the process of memory formation. The initial purpose of these investigations was to determine the molecular basis of the "memory trace" This goal still remains distant, although there are some indications that protein synthesizing systems are involved. This objective, though of enormous interest, is to be regarded as only a necessary first step. Whether new proteins or some other molecules cause the changes in synapses thought to underlie memory, this knowledge of itself will contribute only a beginning to our understanding of the events which account for the functioning of the brain. A determination of the composition of computer components would provide very little information towards unraveling their function. As the experiments proceeded, however, information of a more general nature was being obtained. The identification of different stages of consolidation show how injections of antibiotics can supplement electroconvulsive shock as a way of disrupting the establishment of memory and how it can supplement ablation in destroying memory already laid down in a permanent mode. Applied to larger animals the localization of various regions sensitive or insensitive to the action of the drugs should become more definitive. We hope that such experiments will contribute increasingly to the general problem of brain function.     

Paradoxical fear-increasing effects of tranquilizers: evidence of repression of memory in the rat

Conditioned suppression of feeding, an index of fear, was increased rather than decreased by the administration of benzodiazepine tranquilizers or amobarbital. The drug-induced increase in conditioned fear varied directly with the intensity of the shock used in fear conditioning. The drugs had no fear-increasing effect in unshocked controls or in rats made amnesic by electroconvulsive shock given immediately after fear conditioning. These observations in animals are reminiscent of clinical reports that intraveneous amobarbital facilitates the recall of repressed traumatic experiences. The retrieval of painful memories may be inhibited or repressed in animals as well as in humans. In both cases, tranquilizers may counteract repression by disinhibition of the act of retrieval.     

Retrograde amnesia: electroconvulsive shock effects after termination of rapid eye movement sleep deprivation

Mice that were deprived of rapid eye movement sleep for 2 days immediately after one-trial training in an inhibitory avoidance task and were given an electroconvulsive shock after deprivation displayed retrograde amnesia on a retention test given 24 hours later. Electroconvulsive shock produced no amnesia in comparable groups of animals that were not deprived of rapid eye movement sleep.     

Activity and responsivity in rats after magnesium pemoline injections

Rats injected intraperitoneally with magnesium pemoline avoided a buzzing sound (conditioned stimulus) associated with an electric shock to the feet (unconditioned stimulus) more frequently than controls. Drug-injected rats did not avoid the foot shock more frequently than controls, although the experi mental rats did have shorter response latencies fn the active avoidance task. In sub sequent experiments which measured activity changes and response to the buzzing sound alone, it was found that magnesium pemoline caused a lesser decrease in activity level and a more sustained responsivity to the buzzer's. sound than did control injections of tragacanth. This may account for the latency differences observed in the avoidance task.     

Retrograde amnesia: effects of handling and microwave radiation

Rats that were irradiated with microwaves immediately after the training trial in a one-trial shock-avoidance learning task retained the conditioned avoidance response 24 hours later. However, rats that were handled a few minutes each day for 3 days before the experiment did not retain the response, although they were capable of learning in a later test.     

Effect of electroconvulsive shock on an extinguished "fear" response

To test Gellhorn's hypothesis that electroconvulsive shock reinstates extinguished responses, a conditioned "anxiety" response was established and then extinguished in rats. A series of treatments did not restore the extinguished "anxiety" response; in fact, control animals showed appreciable spontaneous recovery of the "anxiety" response while treated animals did not.     

Puromycin effect on memory may be due to occult seizures

Intracerebral injections of puromycin, which have been shown to impair memory 3 hours after training, increase the susceptibility of mice to seizures after administration of normally subconvulsive doses of pentylenetetrazol. Cycloheximide, which antagonizes the puromycin-induced amnesia 3 hours after training, also antagonizes the puromycin effect on susceptibility to seizure. The anticonvulsant diphenylhydantoin antagonizes the puromycin effect on memory. The puromycin effect on memory may be due to occult seizures.     

Theta rhythm: a temporal correlate of memory storage processes in the rat

We examined the amount of theta rhythm (4 to 9 hertz) in cortical electroencephalograms of rats for 30 minutes after training in one-trial tasks. Some animals received electroconvulsive shock after training. The amount of theta in the electroencephalogram after training was positively correlated with the degree of subsequent retention of a footshock, whether animals had received electroconvulsive shock or not.     

Memory in the Japanese quail: effects of puromycin and acetoxycycloheximide

Intracerebral injections of puromycin produced memory deficits in naive quail trained to discriminate between red and green stimuli. Puromycin aminonucleoside, acetoxycycloheximide, and saline had no such effect. After a single reversal of the visual cues, naive quail treated with puromycin performed better than control birds. Also, puromycin had no effect on performance when injected into previously trained animals. High doses both of puromycin and acetoxycycloheximide inhibited ribonucleic acid and protein synthesis to a similar extent, while low doses of puromycin inhibited only protein synthesis. Since only puromycin inhibited memory, the basis for its effect appears more likely to be mediated by the action of peptidyl-puromycin rather than by the quantitative inhibition of macromolecular synthesis or by some nonspecific toxic action.     

Recovery of memory after amnesia induced by electroconvulsive shock

Electroconvulsive shock given to rats immediately after one-trial avoidance learning produced a significant amnesic effect 24 hours later; this amnesia had largely disappeared in further retention tests 48 and 72 hours after treatment. This result puts in question a basic assumption implicit in most memory consolidation studies that such amnesic effects will be permanent.     

Hippocampal unit activity during classical aversive and appetitive conditioning

Rats were trained with a tone being followed by either food or electric shock, on alternate days. Unit activity during application of the conditioned stimulus was recorded from the dorsal hippocampus. The results indicate differentiation of the hippocampal system. Dentate units respond by augmentation to a conditioned stimulus which leads to food and by inhibition to the same stimulus when it precedes electric shock. The hippocampus proper responds by augmentation in both situations. The intensity of the hippocampal response to the conditioned stimulus on the first day of training is higher if the unconditioned stimulus is food than if it is electric shock. These data cast light on the functions of the dorsal dentate-hippocampal connections and the hippocampus proper during aversive and appetitive conditioning.     

Changes in intensity of punishment: effect on running behavior of rats

Changing the strength of punishment produced only minor changes in rats' speed of running to food and shock at the goal of an alley. The persistence of running behavior after increased or decreased shock intensity is attributed to a stereotyped withdrawal response conditioned at the goal during initial punishment training.