Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002622 (amnesia)
 5,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies using protein synthesis inhibitors have provided key support for the prevalent view that memory formation requires the initiation of protein synthesis as a primary element of the molecular biology of memory. However, many other interpretations of the amnesia data have received far less attention. These include: (a) protein synthesis may play a constitutive role in memory formation, providing proteins prior to an experience that can be activated by training; (b) protein synthesis may be needed to replace proteins available prior to learning but 'consumed' by learning; (c) inhibition of protein synthesis impairs the well-being of neurons, leading to an inability to deliver resources needed for memory formation; and (d) inhibition of protein synthesis results in abnormal neural functions that interfere with memory. One of these, abnormal release of neurotransmitters after inhibition of protein synthesis, is detailed here, along with a review of many circumstances in which it appears that protein synthesis at the time of training is not required for the formation of new memories. Evidence of activation of cell signaling molecules and transcription factors is another form of support for a role of training-initiated protein synthesis in memory. However, recent findings suggest that many of these molecules are activated by training and remain activated for days after training, i.e. activated for times well beyond those typically invoked for memory consolidation processes. Reviewing these results, this paper suggests that the long-lasting molecular changes may be the basis of a form of intracellular memory, one responsible for up-regulating the probability that a neuron, once activated in this manner, will engage in future plasticity. This view melds ideas of modulation of memory with those of consolidation of memory.
Neurobiol Learn Mem 2008 Mar
PMID:Protein synthesis inhibition and memory: formation vs amnesia. 1805 4

In the present study, the possible role of nicotinic acetylcholine (nACh) receptors of the ventral tegmental area (VTA) on morphine-state-dependent learning was studied in adult male Wistar rats. As a model of memory, a step-through type passive avoidance task was used. All animals were bilaterally implanted with chronic cannulae in the VTA, trained using a 1mA foot shock, and tested 24h after training to measure step-through latency. Post-training subcutaneous (s.c.) injection of morphine (0.5-5mg/kg) dose-dependently reduced the step-through latency, showing morphine-induced amnesia. Amnesia induced by post-training morphine was significantly reversed by pre-test administration of morphine (2.5-5mg/kg, s.c.) and induced morphine-state-dependent learning. Pre-test injection of nicotine (0.25-1microg/rat) into the VTA plus an ineffective dose of morphine (0.5mg/kg) significantly restored the memory retrieval. It should be noted that pre-test intra-VTA injection of the same doses of nicotine (0.25-1microg/rat) alone cannot affect memory retention. Furthermore, pre-test intra-VTA injection of the nicotinic acetylcholine receptor antagonist, mecamylamine (1-3microg/rat) 5min before the administration of morphine (5mg/kg, s.c.) dose-dependently inhibited morphine-state-dependent learning. Pre-test injection of the higher dose of mecamylamine (3microg/rat) into the VTA by itself decreased the step-through latency and induced amnesia. On the other hand, mecamylamine (0.5 and 1microg/rat, intra-VTA) reversed the effect of nicotine on morphine response. The results indicate that nACh receptors in the VTA participate in the modulation of morphine-induced recovery of memory, on the test day.
Neurobiol Learn Mem 2008 Jul
PMID:Nicotinic acetylcholine receptors of the ventral tegmental area are involved in mediating morphine-state-dependent learning. 1844 Aug 34

The administration of the ryanodine receptor (RyR) agonist 4-Cmc (0.003-9 nmol per mouse intracerebroventricularly [i.c.v.]) ameliorated memory functions, whereas the RyR antagonist ryanodine (0.0001-1 nmol per mouse i.c.v.) induced amnesia in the mouse passive avoidance test. The role of the type 1, 2, and 3 RyR isoforms in memory processes was then evaluated by inhibiting the expression of the three RyR proteins in the mouse brain. A selective knockdown of the RyR isoforms was obtained by the i.c.v. administration of antisense oligonucleotides (aODNs) complementary to the sequence of RyR1, RyR2 and RyR3 proteins, as demonstrated by immunoblotting experiments. RyR1 (5-9 nmol per mouse i.c.v.) knockdown mice did not show any memory dysfunction. Conversely, RyR2 (1-7 nmol per mouse i.c.v.) and RyR3 (1-7 nmol per mouse i.c.v.) knockdown animals showed an impairment of memory processes. This detrimental effect was temporary and reversible, disappearing 7 d after the end of the aODN treatment. At the highest effective doses, none of the compounds used impaired motor coordination, as revealed by the rota rod test, nor modified spontaneous mobility and inspection activity, as revealed by the hole-board test. In conclusion, the lack of any involvement of cerebral RyR1 was demonstrated. These findings also showed the involvement of type 2 and type 3 RyR in the modulation of memory functions identifying these cerebral RyR isoforms as critical targets underlying memory processes.
Learn Mem 2008 May
PMID:Different involvement of type 1, 2, and 3 ryanodine receptors in memory processes. 1844 Dec 89

Diencephalic amnesia manifests itself through a host of neurological and memory impairments. A commonly employed animal model of diencephalic amnesia, pyrithiamine-induced thiamine deficiency (PTD), results in brain lesions and impairments similar in nature and distribution to those observed in humans with Wernicke-Korsakoff syndrome (WKS). In the current investigation, 2 separate experiments were conducted in which acetylcholine (ACh) efflux was assessed in the hippocampus and striatum of PTD-treated and pair-fed (PF) control male Sprague-Dawley rats. The goal was to determine under what behavioral conditions and in which brain structures ACh efflux was spared, impaired, or adaptively enhanced. In Experiment 1, rats were assessed on a spontaneous alternation task; in Experiment 2, rats were tested on a T-maze discrimination task that could be learned via a hippocampal- or striatal-based strategy. In Experiment 1, PTD-treated rats were impaired on the spontaneous alternation task and ACh efflux in the hippocampus during testing was significantly reduced, but spared in the striatum. In Experiment 2, PTD- and PF-treated rats did not differ in the number of trials to criterion, but PTD-treated rats demonstrated greater reliance upon egocentric cues to solve the task. Furthermore, ACh efflux in the striatum was greater during maze learning in the PTD-treated animals when compared to the PF animals. These results suggest that there is behavioral and systems level plasticity that can facilitate the use of alternative strategies to solve a task following diencephalic damage and WKS.
Neurobiol Learn Mem 2008 Jul
PMID:Impaired, spared, and enhanced ACh efflux across the hippocampus and striatum in diencephalic amnesia is dependent on task demands. 1847 86

Previously acquired aversive and appetitive memories are not stable and permanent. The reactivation of such memories by re-exposure to training stimuli renders them vulnerable to disruption by amnestic agents such as the noncompetitive N-methyl-D-aspartate receptor antagonist (+)-5-methyl-10,11-dihydro-SH-dibenzo{a,d}cyclohepten-5,10-imine maleate (MK-801). However, relatively little is known about the parameters that influence the reactivation process. Here, we show that the method of stimulus presentation during memory reactivation is of great importance. Male Lister Hooded rats were trained to acquire a lever press response that delivered a sucrose reward paired with a light conditioned stimulus (CS). The CS-sucrose association was then reactivated through re-exposure to the CS, either contingently upon the lever press response, or noncontingently in the absence of instrumental responding. Systemic administration of MK-801 (0.1 mg/kg) at the time of memory reactivation resulted in amnesia, and hence a reduction in subsequent sucrose seeking induced by, and dependent upon, presentation of the CS, only when the memory was reactivated contingently. Therefore, stimuli may have to be presented in the same manner at memory reactivation as during learning in order to render a previously acquired memory vulnerable to disruption. These results have important implications for the potential translational use of glutamatergic treatments in conjunction with targeted memory reactivation.
Learn Mem 2008 Jun
PMID:Reactivation-dependent amnesia for appetitive memories is determined by the contingency of stimulus presentation. 1850 12

The temporal dynamics of consolidation and reconsolidation of taste/odor aversion memory are evaluated during rat pup growth at postnatal days 3, 10, and 18. This is assessed through the temporal gradients of efficacy of a protein synthesis inhibitor (anisomycin) in inducing amnesia after either acquisition (consolidation) or reactivation (reconsolidation). The results show a progressive reduction with age of the delay during which the inhibitor is able to induce amnesia. Control experiments rule out a reduction of anisomycin efficacy due to blood brain barrier growth or decrease in protein synthesis inhibition. Thus, these results present the first evidence that the protein synthesis-dependent phase of memory stabilization requires less time with age. This decrease occurs in parallel for consolidation and reconsolidation. Such changes in the dynamics of memory processing could contribute to the cognitive improvement associated with development.
Learn Mem 2008 Jun
PMID:The temporal dynamics of consolidation and reconsolidation decrease during postnatal development. 1851 44

The theory of memory reconsolidation relates to the hypothesized restabilisation process that occurs following the reactivation of a memory through retrieval. Thus the demonstration of reactivation-dependent amnesia for a previously acquired memory is a prerequisite for showing that such a memory undergoes reconsolidation. Here we show that the appetitive Pavlovian representations that underlie Pavlovian approach and Pavlovian-instrumental transfer are destabilized following their retrieval. This reactivation-dependent amnesia demonstrates that the general motivational or incentive properties of appetitive conditioned stimuli, as well as their conditioned reinforcing properties, can be reduced by blocking memory reconsolidation.
Learn Mem 2008 Aug
PMID:Reactivation-dependent amnesia in Pavlovian approach and instrumental transfer. 1868 51

Infusions of CREB antisense into the amygdala prior to training impair memory for aversive tasks, suggesting that the antisense may interfere with CRE-mediated gene transcription and protein synthesis important for the formation of new memories within the amygdala. However, the amygdala also appears to modulate memory formation in distributed brain sites, through mechanisms that include the release of norepinephrine and acetylcholine within the amygdala. Thus, CREB antisense injections may affect memory by interfering with mechanisms of modulation, rather than storage, of memory. In the present experiment, rats received bilateral intra-amygdala infusions of CREB antisense (2 nmol/1 microL) 6 h prior to inhibitory avoidance training. In vivo microdialysis samples were collected from the right amygdala before, during, and following training. CREB antisense produced amnesia tested at 48 h after training. In addition, CREB antisense infusions dampened the training-related release of norepinephrine, and to a lesser extent of acetylcholine, in the amygdala. Furthermore, intra-amygdala infusions of the beta-adrenergic receptor agonist clenbuterol administered immediately after training attenuated memory impairments induced by intra-amygdala injections of CREB antisense. These findings suggest that intra-amygdala treatment with CREB antisense may affect processes involved in modulation of memory in part through interference with norepinephrine and acetylcholine neurotransmission in the amygdala.
Learn Mem 2008 Sep
PMID:Intra-amygdala injections of CREB antisense impair inhibitory avoidance memory: role of norepinephrine and acetylcholine. 1877 55

The effects of hypothermia on memory formation have been examined extensively, and while it is clear that post-training cooling interferes with the process of consolidation, the nature of the temperature sensitive processes disrupted in this way remain poorly defined. Post-training manipulations that disrupt consolidation tend to be effective during specific time-windows of sensitivity, the timing and duration of which are directly related to the mechanism through which the treatment induces amnesia. As such, different treatments that target the same basic processes should be associated with similar time-windows of sensitivity. Using this rationale we have investigated the possibility that cooling induced blockade of long-term memory (LTM) stems from the disruption of protein synthesis. By varying the timing of post-training hypothermia we have determined the critical period during which cooling disrupts the consolidation of appetitive long-term memory in the pond snail Lymnaea. Post-training hypothermia was found to disrupt LTM only when applied immediately after conditioning, while delaying the treatment by 10 min left the 24 h memory trace intact. This brief (<10 min) window of sensitivity differs from the time-window we have previously described for the protein synthesis inhibitor anisomycin, which was effective during at least the first 30 min after conditioning [Fulton, D., Kemenes, I., Andrew, R. J., & Benjamin, P. R. (2005). A single time-window for protein synthesis-dependent long-term memory formation after one-trial appetitive conditioning. European Journal of Neuroscience, 21, 1347-1358]. We conclude that hypothermia and protein synthesis inhibition exhibit distinct time-windows of effectiveness in Lymnaea, a fact that is inconsistent with the hypothesis that cooling induced amnesia occurs through the direct disruption of macromolecular synthesis.
Neurobiol Learn Mem 2008 Nov
PMID:Time-window for sensitivity to cooling distinguishes the effects of hypothermia and protein synthesis inhibition on the consolidation of long-term memory. 1879 38

Interference with activity of numerous cerebral structures produces memory deficiencies; in many instances, however, when animals are over-trained such interference becomes innocuous. Systemic administration of protein synthesis inhibitors impairs long-term retention; this effect has been interpreted to mean that protein synthesis is required for memory consolidation, though little is known about the effect of protein synthesis inhibitors on memory of enhanced learning in the rat. To further analyze the protective effect of enhanced learning against amnesic treatments, groups of Wistar rats were trained in a one-trial step-through inhibitory avoidance task, using different intensities of foot-shock during training. Cycloheximide (CXM; 2.8 mg/kg), an inhibitor of protein synthesis, was injected either 30 min before training or immediately after training. Twenty-four hours after training retention latencies were recorded. Our data showed that both pre- and post-training administration of CXM produced amnesia in those groups that had been trained with relatively low foot-shock intensities, but no impairment in retention was observed when relatively high intensities of foot-shock were administered. These and similar results lead us to conclude that protein synthesis inhibitors may interfere with memory consolidation, but their effect disappears when animals are submitted to an enhanced learning experience, calling into question the idea that protein synthesis is required for memory consolidation.
Neurobiol Learn Mem 2009 Mar
PMID:Enhanced inhibitory avoidance learning prevents the long-term memory-impairing effects of cycloheximide, a protein synthesis inhibitor. 1901 Apr 29


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