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.     

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.     

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.     

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.     

Puromycin: effect on memory of mice when injected with various cations

Puromycin dihydrochloride neutralized with bases of potassium, lithium, calcium, or magnesium fails to block expression of memory of maze learning in mice, unlike puromycin neutralized with NaOH. This failure may be due to cationic binding at anionic membrane sites with a resultant exclusion of sufficient peptidyl-puromycin to make it ineffective in blocking memory.     

The medial temporal lobe memory system

Studies of human amnesia and studies of an animal model of human amnesia in the monkey have identified the anatomical components of the brain system for memory in the medial temporal lobe and have illuminated its function. This neural system consists of the hippocampus and adjacent, anatomically related cortex, including entorhinal, perirhinal, and parahippocampal cortices. These structures, presumably by virtue of their widespread and reciprocal connections with neocortex, are essential for establishing long-term memory for facts and events (declarative memory). The medial temporal lobe memory system is needed to bind together the distributed storage sites in neocortex that represent a whole memory. However, the role of this system is only temporary. As time passes after learning, memory stored in neocortex gradually becomes independent of medial temporal lobe structures.     

Puromycin: action on neuronal mitochondria

Puromycin, in dosages that inhibit cerebral protein synthesis and expression of memory in mice, produces swelling of neuronal mitochondria. Acetoxycycloheximide, which inhibits cerebral protein synthesis to the same extent as puromycin, fails to produce swelling of neuronal mitochondria. Puromycin and heximide mixtures produce severe inhibition of protein synthesis, but result in a minimal swelling of neuronal mitochondria and in a decrease of peptidylpuromycin complexes to a level of 30 percent of that following the injection of puromycin alone. It is concluded that swelling of neuronal mitochondria in the presence of puromycin is not due to inhibition of cerebral protein synthesis per se, but is related to a specific action of puromycin on ribosomal protein synthesis. The findings are consistent with the hypothesis that peptidyl-puromycin complexes are responsible for mitochondrial swelling.     

Sites of neocortical reorganization critical for remote spatial memory

The hippocampus is crucial for spatial memory formation, yet it does not store long-lasting memories. By combining functional brain imaging and region-specific neuronal inactivation in mice, we identified prefrontal and anterior cingulate cortices as critical for storage and retrieval of remote spatial memories [correction]. Imaging of activity-dependent genes also revealed an involvement of parietal and retrosplenial cortices during consolidation of remote memory. Long-term memory storage within some of these neocortical regions was accompanied by structural changes including synaptogenesis and laminar reorganization, concomitant with a functional disengagement of the hippocampus and posterior cingulate cortex [correction]. Thus, consolidation of spatial memory requires a time-dependent hippocampal-cortical dialogue, ultimately enabling widespread cortical networks to mediate effortful recall and use of cortically stored remote memories independently.     

Reticuloendothelial blockade: effect of puromycin on opsonin-dependent recovery

Reticuloendothelial blockade induced by the administration of a gelatinized "reticuloendothelial test lipid emulsion" is due to a loss of opsonic activity in the plasma. Recovery from blockade, which is associated with restoration of plasma opsonins, was inhibited by the administration of puromycin. The effect of puromycin appears to be mediated by inhibition of opsonin formation rather than a puromycin-induced macrophage defect in phagocytosis.     

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.     

Effects of serotonin on memory impairments produced by ethanol

Subjects treated with low or high doses of ethanol demonstrated impaired memory, particularly in tests involving the recall of poorly learned information. Zimelidine, an inhibitor of serotonin reuptake, reversed this ethanol-induced impairment. The serotonin neurotransmitter system may mediate learning and memory in humans and may determine some of the effects of alcohol on higher mental functions.     

Amnesia or reversal of forgetting by anticholinesterase, depending simply on time of injection

The effect of intracerebral injections of the anticholinesterase drug diisopropyl fluorophosphate in rats was to produce good recall of an otherwise almost forgotten habit learned 28 days before. The same injections produced temporary amnesia for the same habit, otherwise well remembered, learned 14 days before. The injections had no ef fect on the memory of the same habit when it was only partly learned 14 days before. The results support the hy pothesis that the physiological basis of memory lies in an increase, and for getting in a decrease, in synaptic con ductance.     

Lesions of central norepinephrine terminals with 6-OH-dopamine: biochemistry and fine structure

Intracisternal injections of 6-hydroxydopamine produce rapid and long-lasting depletion of brain catecholamines without effects on serotonin concentrations. Depletion of norepinephrine is greatest in areas containing only nerve terminals and axons and least in areas containing monoamine cell bodies. The norepinephrine loss is accompanied by electron microscopic evidence of nerve terminal degeneration and decreased turnover. Dopamine loss is less marked and is not accompanied by degeneration or alteration of turnover rate.     

Puromycin and cycloheximide: different effects on hippocampal electrical activity

Abstract. Mice were injected in the temporal region of the brain with cycloheximide or puromycin; both agents markedly inhibit protein synthesis in the brain. Recordings of electrical activity were made in the hippocampal region 5 hours after injection of these drugs. The amplitude and frequency observed in records from mice injected with cycloheximide were indistinguishable from those injected with saline alone. Records from puromycin-injected mice were strikingly abnormal. This finding may contribute to the differences in behavioral effects of intracerebral injections of the two inhibitors of protein synthesis studied.     

Cholinergic enhancement and increased selectivity of perceptual processing during working memory

Using functional magnetic resonance imaging, we investigated the mechanism by which cholinergic enhancement improves working memory. We studied the effect of the cholinesterase inhibitor physostigmine on subcomponents of this complex function. Cholinergic enhancement increased the selectivity of neural responses in extrastriate cortices during visual working memory, particularly during encoding. It also increased the participation of ventral extrastriate cortex during memory maintenance and decreased the participation of anterior prefrontal cortex. These results indicate that cholinergic enhancement improves memory performance by augmenting the selectivity of perceptual processing during encoding, thereby simplifying processing demands during memory maintenance and reducing the need for prefrontal participation.     

Behavioral effects in monkeys of racemates of two biologically active marijuana constituents

Both dl-Delta(8)- and dl-Delta(9)-tetrahydrocannabinol produced marked alterations of behavior in rhesus and squirrel monkeys. Squirrel monkeys appeared to have visual hallucinations. Continuous avoidance behavior of squirrel monkeys was stimulated by both drugs, but high doses of dl-Delta(9)-tetrahydrocannabinol also caused depression after the stimulant phase. Complex behavior involving memory and visual discrimination in rhesus monkeys was markedly disrupted by both drugs.     

威海雷电灾害分布及成因分析

利用威海气象局1997—2017年雷电灾害统计资料,分析威海市雷电灾害的主要形式、经济损失、伤亡人数、时空分布特征、行业特征和地域差异,并对灾害成因做了进一步的分析。结果表明,雷灾事故相对发生较多的地区为威海中部及西部内陆地区,雷灾事故相对发生较少的地区为东部及南部沿海地区;年雷电灾害次数总体呈上升趋势;雷电造成的损害有直接雷击灾害和间接雷击灾害,其中间接雷击造成的损失占79.44%;每年5—8月是威海雷电灾害事故高发时期,每天15:00—17:00是雷电灾害事故高发时段;雷击造成微电子设施损失位居榜首,供配电设施次之;郊区雷击时常造成人员伤亡事故,应引起特别关注。     

Alzheimer's disease: cell-specific pathology isolates the hippocampal formation

Examination of temporal lobe structures from Alzheimer patients reveals a specific cellular pattern of pathology of the subiculum of the hippocampal formation and layers II and IV of the entorhinal cortex. The affected cells are precisely those that interconnect the hippocampal formation with the association cortices, basal forebrain, thalamus, and hypothalamus, structures crucial to memory. This focal pattern of pathology isolates the hippocampal formation from much of its input and output and probably contributes to the memory disorder in Alzheimer patients.     

Memory-blocking agents: effects on olfactory discrimination in homing salmon

Homing salmon were injected intracranially with puromycin, actinomycin D, or cycloheximide. From 4 to 7 hours after such treatment these agents markedly inhibited olfactory bulbar discrimination between home water and other natural waters, including spawning sites for other groups of salmon. At longer intervals after treatment there was a partial restoration of olfactory memory-based discrimination. The dosages of the inhibitors used could be shown to have depressed incorporation of H(3)-leucine into protein by 78 percent or of H(3)-uridine into RNA by 41 percent in the salmon brains 4 hours after intracranial injection. These findings suggest that acute blockage of RNA synthesis or protein synthesis can interfere with long-term olfactory memory in anadromous salmon, at least as this function can be analyzed by electrophysiological methods. This implies that long-term olfactory memory depends upon continued metabolism of RNA and continued protein synthesis.     

Overeating and obesity from damage to a noradrenergic system in the brain

A discrete, ascending fiber system that supplies the hypothalamus with most of its noradrenergic terminals was destroyed at midbrain level, both electrolytically and with local injections of 6-hydroxydopamine, a destructive agent specific for catecholaminergic neurons. The result was hyperphagia leading to obesity. Fluorescence histochemical analysis showed that loss of noradrenergic terminals in ventral bundle termination areas such as the hypothalamus was necessary for hyperphagia. Damage to dorsal bundle or dopaminergic projections was not. Prior treatment with desmethylimipramine to selectively block uptake of 6-hydroxydopamine into noradrenergic neurons prevented both hyperphagia and loss of norepinephrine fluorescence. The lesions that produced hyperphagia also reduced the potency of d-amphetamine as an appetite suppressant. It is concluded that this noradrenergic bundle normally mediates suppression of feeding, thereby influences body weight, and serves as a substrate for d-amphetamine-induced loss of appetite.