Limited period of action of testosterone on memory formation in the chick.

Domestic chicks will normally peck readily at small colored beads. However, a peck at a bead with an unpleasant taste usually results in a long-lasting aversion to beads of that type. The present study describes experiments in which pretraining and training were separated by a standard interval and then followed by retention tests at varying times in different groups of Warren sex-link chicks. The effect of variation in the interval between pretraining and training is also examined. Results show that if prior experience ("pretraining") of a bead of the type that is to be used in a later aversive training trial is given to testosterone-treated Ss, it interferes with the retention of avoidance. Interference by pretraining is effective only within sharply defined periods of time: when the pretraining–training interval is either less than 2 min (short-term) or greater than about 25 min (long-term). When pretraining and training are separated by 90 min or more, the steroid can be effective when injected up to 30 min after pretraining. It appears to change the character of the consolidating memory trace of pretraining in such a way as to make the consolidation of later, contradictory information from training less likely. The initial stage of this information is apparantly unaffected, since retention does not begin to decay until 30–60 min after training. Short-term interference leads to loss of avoidance within 5 min of training and can be used to demonstrate that the latency of action of the hormone in this task is less than 20 min following a sc injection. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of apomorphine and haloperidol on memory consolidation in the day-old-chick.

Apomorphine was found to disrupt memory consolidation in a dose–dependent manner on chicks trained on a 1-trial passive avoidance task with a strong aversant experience. Chicks injected with 4.0 mg/kg apomorphine displayed memory deficits at 180 min after learning and showed marked behavioral disturbances, including increased locomotion and increased pecking at the feet of conspecifics. Pretreatment with the dopamine antagonist haloperidol eliminated the memory disturbance induced by apomorphine and facilitated consolidation of memory in chicks given a weak (20% vol/vol methyl anthralinate) training experience. Time-of-retention data suggested that the memory disruption occurred from 120 min after learning, leading to the suggestion that dopamine–related modulation of the training experience may be involved in late-memory formation processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogenetic differences in the expression of conditioned stimulus conditioning: effects of retention interval

Preweanling 17-day-old rats were tested for retention of the conditioned emotional response after a 5-min or 24-hr retention interval. For a variety of conditioning parameters (i.e., variation in conditioned stimulus modality, unconditioned stimulus intensity, number of training trials), conditioned responding was consistently weaker after 5 min than after 24 hr. This apparent "incubation," or "hypermnesic," effect was not found in adult rats, even when comparable conditioning levels were indicated on the 24-hr test. The transient short-term retention deficit observed in 17-day-old preweanlings was alleviated by placing the pup in its home cage during the 5-min retention interval or by extending the conditioning session. Fifteen-day-old rat pups did not benefit from home cage exposure or extended training and displayed the transient short-term retention deficit regardless. The results are discussed in terms of age-related effects on time-dependent memory consolidation.     

Delaying interference enhances memory consolidation in amnesic patients.

Some patients with amnesia are able to retain new information for much longer than expected when the time that follows new learning is devoid of further stimuli. Animal work shows that the absence or delaying of interference improves long-term memory consolidation. Our study suggests that this is also true for at least some patients with amnesia. Retention of new verbal material was significantly higher in a sample of patients with amnesia (N = 12) when interference occurred at the end of a 9-min delay interval than when it occurred in the middle or at the beginning of the interval. Such findings cannot be accounted for by the mere use of explicit short-term memory rehearsal. Any such rehearsal should have been blocked by the interference, irrespective of interference onset, thus leading to poor retention in all three conditions. The current findings suggest that at least some of the severe forgetting observed in amnesia is the product of a disruption of memory consolidation by immediate postlearning interference. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibition of cerebral protein synthesis does not prolong short-term memory.

In 4 experiments, male Swiss-Webster CD-1 mice were given a single sc injection of a cerebral protein synthesis inhibitor, anisomycin (ANI, 1 mg/S), 20 min prior to a single trial of passive avoidance training. Ss demonstrated impaired retention at test given 3 hrs, 6 hrs, 1 day, and 7 days after training. Retention was not significantly different from that of saline controls when tests were given .5 or 1.5 hrs after training. Prolonging inhibition of brain protein synthesis by giving either 1 or 2 additional injections of ANI at 2 hrs or at 2 and 4 hrs after training did not prolong good retention performance. The temporal development of impaired retention in ANI-treated Ss could not be accounted for by drug dosage, duration of protein synthesis inhibition, or nonspecific sickness at test. In contrast to the suggestion that protein synthesis inhibition prolongs short-term memory, these results indicate that short-term memory is not prolonged by antibiotic drugs that inhibit cerebral protein synthesis. All evidence seems consistent with the hypothesis that short-term memory is independent of protein synthesis and that the establishment of long-term memory depends on protein synthesis during or shortly after training. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Different temporal profiles of amnesia after intra-hippocampus and intra-amygdala infusions of anisomycin.

Systemic or intra-hippocampal administration of the protein synthesis inhibitor anisomycin generally leads to impairments in memory tested 24 hr or more after training but spares memory for a few hours after training. Thus, amnesia does not appear immediately after training but develops with time, findings most often interpreted as evidence for distinct short- and long-term memory processes. However, time courses for the onset of amnesia vary substantially after treatment with protein synthesis inhibitors. Some of the variability across experiments may reflect task-related differences or, perhaps relatedly, may reflect memory processing mediated by different neural systems. In the present experiments, anisomycin was infused into either the hippocampus or the amygdala 20 min before inhibitory avoidance training. Similar to previous findings, intra-hippocampus injections of anisomycin impaired memory tested 48 hr after training yet spared memory tested 4 hr after training. In contrast, intra-amygdala injections of anisomycin impaired memory tested at 0.5, 4, and 48 hr after training, revealing no evidence for spared memory at short times after training. The distinct temporal properties for amnesia following anisomycin injections into the hippocampus or amygdala may reflect different consequences for memory of perturbations of the neural system in which the manipulation is made. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of lysine-8-vasopressin on retention and retrieval of a discrimination reward task in the rat.

The effect of vasopressin on memory of a brightness discrimination reward task was investigated in 20 male Sprague-Dawley rats. Two measures of retention were used: resistance to extinction and savings scores on a reacquisition task given 45 days after the completion of extinction training. The effect of the peptide on both memory consolidation and retrieval was assessed. There were 2 major findings: (a) The peptide enhanced memory consolidation of the task whether measured after a short time interval (6 days) or after a long time interval (45 days after completion of extinction training) using a measure of trials to relearn the task, and (b) the peptide had no effect on memory retrieval. These results were compared to those of other studies designed to access memory consolidation and retrieval on appetitive tasks. The mechanisms of the peptide's effect on memory was briefly discussed with respect to three theories on the subject. This study extends the vasopressin research on memory consolidation by suggesting that it pertains to appetitive as well as to aversive tasks. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reversible inactivation of the median raphe nucleus enhances consolidation and retrieval but not acquisition of passive avoidance learning in rats

Involvement of median raphe nucleus (MRN) in acquisition, consolidation and retrieval of passive avoidance (PA) was investigated with functional suppression of this area by lidocaine. Rats carrying a chronically implanted cannula aimed at the MRN were trained on a step-through passive avoidance task and received intra-MRN injection of lidocaine or saline 5 min before training or 5, 90 and 360 min after acquisition trial or 5 min before the retrieval test. Lidocaine MRN inactivation had no effect on PA learning. Lidocaine injected 5 and 90 min after the acquisition trial significantly enhanced avoidance of the dark compartment in comparison with the control group injected with saline. But PA retention was not affected by lidocaine injected 360 min after acquisition or 5 min before training. Retention latency significantly increased, when lidocaine injected 5 min before retrieval test. Step-through latency of naive rats was not affected by MRN blockade. Furthermore, reversible inactivation of MRN did not have a significant effect on locomotor activity. Our results indicate that the MRN contributes to PA consolidation at least until 90 min after acquisition and involves in PA retrieval. It is concluded that functional ablation of the MRN may disrupt the inhibitory actions of MRN projections to sub-cortical circuits participating in PA memorization and retrieval.     

Subamnesic cycloheximide treatment delays consolidation in mice.

In Exp I, groups of C57 BL/6J mice were given passive avoidance training and then administered different doses of cycloheximide (CYC) immediately, 30 min, or 1 hr after training. Only the highest dose (150 mg/kg) administered immediately or 30 min after training impaired memory when the mice were tested 72 hrs after training. In Exp II, Ss were given a nonamnesic administration of CYC (30 mg/kg) or saline immediately after training and another injection of CYC (15, 30, or 75 mg/kg) or saline 1 hr after training. The combinations of 30 mg/kg?+?30 mg/kg and 30 mg/kg?+?75 mg/kg impaired memory. Exp III demonstrated that brief carbon dioxide anesthetization initiated immediately after training impaired memory. In Exp IV, mice were given either saline or 30 mg/kg CYC immediately after training and then subjected to either air or CO? anesthetization 30 min after training. Only the group given 30 mg/kg CYC?+?CO? was amnesic when tested 72 hrs after training. Results indicate that the administration of a nonamnesic dose of CYC immediately after training renders the memory susceptible to disruption by additional doses of CYC or other amnesic treatments for a longer period of time than normal. It is suggested that CYC delays consolidation and prolongs the labile period of memory formation. (11 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Salbutamol overcomes the effect of the noradrenergic neurotoxin DSP-4 on memory function in the day-old chick

These experiments investigated the effect of the relatively selective noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) on memory formation in day-old chicks trained on a discriminated passive avoidance task. A time course study showed that DSP-4 treatment resulted in amnesia as early as 20 min post-learning. In a second study, a series of alpha- and beta-adrenergic agonists (noradrenaline; the alpha 1 agonist phenylephrine; the beta 1 agonist dobutamine; and the beta 2 agonist salbutamol) were applied immediately after the training trial. Both noradrenaline and salbutamol were effective in ameliorating the memory deficits caused by DSP-4 treatment, and in consolidating weakly reinforced training. These studies support the notion that noradrenaline subserves a vital role in the consolidation of memory in the chick, and that the beta 2 receptor subtypes are principally involved in the intermediate phase of memory formation.     

The demonstration of short-term consolidation

In a dual-task paradigm, a visual display (T1) containing characters (letters or symbols) was presented first, followed by an auditory signal (T2) at various stimulus-onset asynchronies (SOAs). A speeded response to T2 was required. When the information in T1 had to be recalled later, response times to T2 (RT2) were elevated at short SOAs and decreased as SOA was increased. The effects on RT2 were larger when there were more items to be remembered. We interpreted the results as evidence that encoding information into short-term memory (STM) involves a distinct process, which we call short-term consolidation (STC). The results suggested that STC has limited capacity and that it requires central processing mechanisms. Additional evidence suggested that no memory for T1 was formed in STM when STC was not engaged.     

Ontogeny of contextual fear conditioning in rats: Implications for consolidation, infantile amnesia, and hippocampal system function.

Presents developmental evidence that contextual fear conditioning is supported by a short-term memory system that supports conditioning immediately after a shock and by a long-term memory system that supports contextual conditioning 24 hrs after training. This is based on the finding that after 1 conditioning trial, rats 18–32 days old show the same amount of conditioned freezing when tested immediately after conditioning but 18-day-old rats show much less conditioned freezing than the older rats when the retention interval is 24 hrs. The data also suggest that the long-term memory representation of context that mediates conditioned fear is not available until several hours after the conditioning trial. Implications of these findings for memory consolidation processes, infantile amnesia, and hippocampal formation development are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long gradient of retrograde amnesia in mice: Continuity with the findings in humans.

560 male albino mice were given a single training trial and then received either sham treatment or 4 ECS treatments at hourly intervals at 1 of 7 times (1–70 days) after training. Retention was always tested 2 wks after treatment. Controls exhibited gradual forgetting with increasing retention intervals. Ss given ECS exhibited severe retrograde amnesia, which diminished as the interval between training and ECS increased from 1 to 21 days. ECS given 21–70 days after training had no effect on memory. The finding of long, temporally graded retrograde amnesia in mice establishes continuity between the results for laboratory animals and those for humans and indicates that the neural changes involved in the consolidation of memory can continue for a significant portion of the lifetime of a memory. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of nitric oxide in passive avoidance learning

The role of nitric oxide on passive avoidance learning was studied by administering L-arginine or D-arginine to male rats in a passive avoidance paradigm. L-Arginine administered into the lateral brain ventricle at a dose of 1.25 microg showed a tendency to increase the passive avoidance latency, and 2.5 microg exerted almost maximal action, but the action gradually increased still further up to 20 microg tested. D-Arginine had no action. Peripheral administration (intraperitoneal) of L-arginine facilitated the consolidation of passive avoidance learning in a dose-dependent manner. A significant increase in passive avoidance response was obtained following an injection of 100 mg/kg L-arginine. When L-arginine was given i.c.v. with a selected dose of 5 microg, 30 min prior to a learning trial, the latency of the passive avoidance response was likewise lengthened. However, when L-arginine was given 30 min before the 24-hr testing (retrieval), it was ineffective. It was also ineffective when given 6 hr after the training trial. However, when L-arginine was administered immediately following the training trial, the action in improving the consolidation could be detected 6 hr after the training trial. Nitro-L-arginine, which blocks nitric oxide synthase, can also block the facilitation of consolidation caused by the nitric oxide donor L-arginine. The nitric oxide synthase inhibitor per se in different doses had no action on the learning of a passive avoidance task. The results indicate that nitric oxide is able to facilitate the learning and consolidation of memory in a passive avoidance paradigm, but it is ineffective in retrieval processes. The results also suggest that, under the experimental circumstances used, nitric oxide is involved only in the facilitated learning and memory processes caused by pharmacological effect of L-arginine, and not involved in normal learning processes.     

Delayed extinction attenuates conditioned fear renewal and spontaneous recovery in humans.

This study investigated whether the retention interval after an aversive learning experience influences the return of fear after extinction training. After fear conditioning, participants underwent extinction training either 5 min or 1 day later and in either the same room (same context) or a different room (context shift). The next day, conditioned fear was tested in the original room. When extinction took place immediately, fear renewal was robust and prolonged for context-shift participants, and spontaneous recovery was observed in the same-context participants. Delayed extinction, by contrast, yielded a brief form of fear renewal that reextinguished within the testing session for context-shift participants, and there was no spontaneous recovery in the same-context participants. The authors conclude that the passage of time allows for memory consolidation processes to promote the formation of distinct yet flexible emotional memory traces that confer an ability to recall extinction, even in an alternate context, and minimize the return of fear. Furthermore, immediate extinction can yield spontaneous recovery and prolong fear renewal. These findings have potential implications for ameliorating fear relapse in anxiety disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased immune activation precedes the inflection point of CD4 T cells and the increased serum virus load in human immunodeficiency virus infection

In sickness-conditioned learning, animals become ill after sampling a new substance and develop an aversion that is expressed as avoidance of that substance in subsequent presentations. We examined the parameters of a one-trial, nongustatory, sickness-conditioned learning task in day-old chicks. Chicks pecked a bead and were made ill by i.p. injection of lithium chloride (LiCl). Both 0.5 and 1.0 M LiCl (0.1 ml) produced reliable avoidance at test. Chicks injected with LiCl between 15 and 45 min after training avoided the bead at test, whereas those injected within 5 or 10 min or more than 45 min after training did not. Avoidance was present until 24 h posttraining and absent after 48 h. Therefore, robust learning of the sickness-conditioned learning task occurs in one trial without the need for gustatory cues, and memory for the task lasts at least 24 h. Uses of this task to study memory formation in the day-old chick are discussed.     

The effects of anandamide on memory consolidation in mice involve both D1 and D2 dopamine receptors

Post-training administration of anandamide (1.5, 3, 6 mg/kg) dose-dependently impairs the retention of an inhibitory avoidance response in mice. The effects on retention performance induced by the drug appear to be due to an effect on memory consolidation, as they were observed when drugs were given at short, but not long, periods of time after training, i.e. when the memory trace was susceptible to modulation. Pretreatment with either selective D1 or D2 dopamine (DA) receptor agonists, SKF 38393 and quinpirole, at doses that were ineffective when given alone (5 and 0.25 mg/kg, respectively), antagonized the effects of anandamide on memory consolidation, suggesting that D1 and D2 receptors are similarly involved in the effects of anandamide on memory consolidation. These results are discussed in terms of a possible inverse relationship between the modulation of memory processes by endogenous cannabinoid and DA systems.     

Increased GABAergic activity in the region of the pedunculopontine and deep mesencephalic reticular nuclei reduces REM sleep and impairs learning in rats.

Newly formed memories are initially fragile and require consolidation to be transformed into an enduring state. Memory consolidation may occur during increased postlearning REM sleep. REM deprivation during these periods (termed REM sleep windows [RSWs]) impairs subsequent performance. The pedunculopontine nucleus (PPT) and adjacent deep mesencephalic reticular nuclei (DpMe) have been implicated in the generation of REM sleep. Following 24-hr baseline recording, rats were trained on the 2-way avoidance task for 50 trials/day over 2 days and retested on Day 3. EEG was recorded 22 hr after training on training Days 1 and 2. Rats were injected with the GABAB agonist baclofen or saline into the PPT/DpMe region at 0300 to coincide with the start of a known RSW. Based on shuttle performance, saline rats were assigned post hoc to a learning group (LG) that avoided the footshock at least 60% at retest or nonlearning group (NLG) that performed below this criterion. Baclofen-injected rats were not assigned post hoc into separate groups as all rats performed below the learning criterion. PPN/DpMe infusions of the inhibitory GABAB agonist baclofen decreased REM and impaired subsequent memory performance. Normal GABAergic transmission in the PPN/DpMe may be necessary for REM to occur and for the consolidation of incentive learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Competitive short-term and long-term memory processes in spatial habituation.

Exposure to a spatial location leads to habituation of exploration such that, in a novelty preference test, rodents subsequently prefer exploring a novel location to the familiar location. According to Wagner's (1981) theory of memory, short-term and long-term habituation are caused by separate and sometimes opponent processes. In the present study, this dual-process account of memory was tested. Mice received a series of exposure training trials to a location before receiving a novelty preference test. The novelty preference was greater when tested after a short, rather than a long, interval. In contrast, the novelty preference was weaker when exposure training trials were separated by a short, rather than a long interval. Furthermore, it was found that long-term habituation was determined by the independent effects of the amount of exposure training and the number of exposure training trials when factors such as the intertrial interval and the cumulative intertrial interval were controlled. A final experiment demonstrated that a long-term reduction of exploration could be caused by a negative priming effect due to associations formed during exploration. These results provide evidence against a single-process account of habituation and suggest that spatial habituation is determined by both short-term, recency-based memory and long-term, incrementally strengthened memory. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Temporally graded retrograde amnesia of contextual fear after hippocampal damage in rats: within-subjects examination

We have shown previously that electrolytic lesions of the dorsal hippocampus (DH) produce a severe deficit in contextual fear if made 1 d, but not 28 d, after fear conditioning (). As such, the hippocampus seems to play a time-limited role in the consolidation of contextual fear conditioning. Here, we examine retrograde amnesia of contextual fear produced by DH lesions in a within-subjects design. Unlike our previous reports, rats had both a remote and recent memory at the time of the lesion. Rats were given 10 tone-shock pairings in one context (remote memory) and 10 tone-shock pairings in a distinct context (with a different tone) 50 d later (recent memory), followed by DH or sham lesions 1 d later. Relative to controls, DH-lesioned rats exhibited no deficit in remote contextual fear, but recent contextual fear memory was severely impaired. They also did not exhibit deficits in tone freezing. This highly specific deficit in recent contextual memory demonstrated in a within-subjects design favors mnemonic over performance accounts of hippocampal involvement in fear. These findings also provide further support for a time-limited role of the hippocampus in memory storage.