Search

Recent research has pointed to a role for brain-derived neurotrophic factor (BDNF) in long-term potentiation and memory. The present series of experiments examined the effects of the application of exogenous BDNF on memory consolidation and reconsolidation of a weak training stimulus with the day-old chick, using the passive avoidance learning paradigm. Chicks injected intracranially with 12.5 μg/mL recombinant BDNF immediately after a single-trial training event displayed enhanced retention relative to saline up to 24h post-training. Furthermore, this dose was also shown to enhance retention when administered following initial weak training. Thus, exogenous BDNF was shown to enhance both consolidation and reconsolidation of memory when administered acutely to the day-old chick., (Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.)

Memantine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist that has been approved for the treatment of the cognitive deficits noted in Alzheimer's disease. While there is a body of research that supports memantine's facilitative action upon memory compromise, this series of studies aimed to investigate the effects of this drug in healthy animals with intact memory functioning. A 0.1 mM dose of memantine injected immediately after a weakly aversive training event (i.e. 20% v/v methyl anthranilate) was found to enhance passive avoidance learning for this event in day-old chicks up to 24 h following training. The same dose of memantine was also observed to enhance memory for the training event when it was administered in conjunction with a reminder trial. These results suggest that memantine is capable of facilitating both memory consolidation as well as memory reconsolidation. It was concluded that memantine's mechanism may involve the short-term or intermediate memory phases of the Gibbs and Ng model of memory, and that the current findings represent enhancement of intact memory, rather than amelioration of memory compromise., (Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.)

This series of experiments investigated the role of protein translation and RNA synthesis on consolidation and reconsolidation of passive avoidance learning (PAL) in day-old chicks. Although it is well established that protein translation is required after a reminder, there are conflicting reports in the literature concerning the requirement for RNA synthesis at this time. Day-old male New HampshirexWhite Leghorn chicks were trained on a single trial passive avoidance task. The results confirmed the requirement for protein translation during reconsolidation with memory deficits induced by anisomycin (ANI) (10mg/kg) detected at 60min post-reminder. It was also established that RNA synthesis was required for consolidation of PAL through inhibition by 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) (0.075microg/kg), administered at or after training. The same dose of DRB was also found to inhibit memory post-reactivation. However injections were required before the reminder trial and memory deficits were evident by 60min, consistent with that found for ANI post-reminder. As with ANI, the DRB-induced memory deficit post-reminder was also transient, and resolved by 24h post-reminder. For both reconsolidation drug studies, the memory deficit was wholly dependent on the memory being reactivated by a reminder-trial. The study highlights an important role for RNA synthesis following memory reactivation.

This series of studies examined the effect of the PDE4 inhibitors rolipram and YM976 on the recall of the passive avoidance learning (PAL) task in the day old chick, with a particular focus on the role of D1 receptor in activating this pathway. The results indicated that 2.0 mg/kg rolipram administered 5 min before or immediately, 5, 15 or 30 min following training and 0.025 mg/kg YM976 administered 15 min before or immediately, 5, or 15 min following training facilitated recall of the weak form of the task (i.e. using 20% v/v methyl anthranilate (MeA) as the aversant) at 180 min following training. In each case the effect emerged from 60 min following the training, and was still observable from 180 min to 24 h after training. In addition, whilst administration of 0.5 mg/kg SCH23390, a D1 receptor antagonist, 10 min prior to training disrupted recall for the strong form of the task, co-administration of 2.0 mg/kg rolipram but not 0.025 mg/kg YM976 5 min prior to training prevented this disruption occurring. The results suggest a role for D1 receptor activation in the processes underlying the facilitation of memory by rolipram.

Gamma-butyrolactone (GBL) is a prodrug to gamma-hydroxybutyric acid (GHB) and metabolises to GHB when ingested. Discrimination stimulus studies report generalisation of effects of GHB to GBL. While amnesia is one of the most commonly reported symptoms of GHB's ingestion in human users, as yet few studies have examined this effect. Although an endogenous GHB specific receptor is present in the brain, several studies have indicated that the clinical effects of exogenous doses of GBL/GHB are due to its action on GABA(B) receptors rather than on the GHB receptor. In this series of studies, New Hampshire x White leghorn cockerels were trained using a modified version of the passive avoidance learning task. Subcutaneous injections of GBL induced a memory deficit by 10 min post-training, which persisted for at least 24 h. No effect on memory was seen with administration of the specific GHB agonist NCS-356 (gamma-p-chlorophenyl-trans-4-hydroxycrotonate). The GBL-induced memory deficit appeared similar to the deficit produced by baclofen, where the antagonist facilitated learning. Additionally, GBL-induced memory deficit was ameliorated by application of a GABA(B) antagonist. The results support the hypothesis that GBL exerts its influence on memory via the GABA(B) receptor rather than by the specific GHB receptor.

Both NMDA and non-NMDA receptors participate in the consolidation of passive avoidance learning (PAL) in the day-old chick. NMDA antagonists have also been implicated in reconsolidation processes following reminder-trials. In this study, we examined the effect of administering 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist, on reconsolidation following memory reactivation. New Hampshire x White leghorn cockerels were trained using a modified version of the PAL task. When CNQX was administered 20 min following a reminder trial, a retention deficit was detected at 90 min, but this had resolved by 24 h following the reminder. The parameters of the reconsolidation deficit were similar to those induced by CNQX injections post-training with the exception of their transience. This finding suggests that the action of non-NMDA receptors may perform a similar role in both consolidation and reconsolidation processes.

A one-trial learning task, where chicks learn that a bead of a particular shape and/or colour has a bitter taste (because it has been coated in 100% methyl anthranilate, MeA) and subsequently avoids it on test, has been widely used by research groups across the world. However, there are some differences in the results reported by different research laboratories. One important difference is found when chicks are trained with a diluted bitter taste on the bead (10 or 20% MeA); memory is not consolidated and fades, lasting for different times. At Monash and La Trobe Universities, memory lasts for 30 min but at the Open University (OU), memory lasts for 4-6h before fading. Differences in protocol that may explain this apparent discrepancy are whether the chicks have seen the bead before (novelty) and whether the colour or the shape of the bead is an important feature. In this review, we discuss these and other factors that may contribute to the differences in the characteristics of memory processing at Monash and at the OU, such as chick strain, hatchery or laboratory incubated chicks, age at training. It is clear that there is a difference between passive avoidance and discriminative avoidance protocols and this may explain the differences in duration of the memory with weakly reinforced learning. Is the OU task a more salient experience because of the novelty of the bead and therefore a 'stronger' learning experience? The different protocols may allow different questions to be addressed.

This study investigated the effect of ouabain, an inhibitor of NA(+) and K(+) ATPase, on consolidation and reconsolidation of a passive avoidance learning task in the day-old chick. In the consolidating trace, ouabain is thought to inhibit an intermediate-term memory phase, some aspects of which acts as a "trigger" for long-term stabilisation of the trace by new protein synthesis. It was hypothesised that a similar process may initiate the protein synthesis observed following reminder-activated reconsolidation in the young chick. Chicks were trained on a single trial passive avoidance task. A dose of 0.2 ug/kg ouabain was administered intracranially either 5 min post-training (consolidation processes) or 5 min post-reminder (reconsolidation processes). Consistent with previous research, ouabain administration induced a memory deficit following the initial learning trial. However, contrary to expectation, ouabain did not disrupt memory processing post-reactivation. This finding provides further evidence for the notion that consolidation and reconsolidation are associated with similar, but distinct, stages of processing.

Anecdotal and experimental evidence has demonstrated that humans and animals exhibit physiological and cognitive alterations in response to sickness and injury. It is now clear that these changes are due to the actions of proinflammatory cytokines. The current study examined the effects of peripheral administration of polyinosinic:polycytidylic acid, a synthetic double-stranded viral RNA, on the memory processes of day-old chicks trained on a single trial passive avoidance task. Polyinosinic:polycytidylic acid impaired performance on the passive avoidance task in a dose-dependent manner. Maximal deficits were observed when 5 g/kg polyinosinic:polycytidylic acid was administered 120 min before training. Tests for retention revealed that interference in memory consolidation appeared between 30 and 40 min after training. These results indicate an inhibitory effect of polyinosinic:polycytidylic acid on the processes of memory formation at the transition from intermediate-term memory phase (A) to intermediate-term memory phase (B) of the Gibbs and Ng model of memory formation. The study also investigated the pyrogenic actions of polyinosinic:polycytidylic acid, and examined the effect of pretreatment with ketoprofen, a cyclooxygenase inhibitor. Significant rises in body temperature were observed 30 min after injection of polyinosinic:polycytidylic acid. Inhibition of cyclooxygenase by ketoprofen ameliorated the polyinosinic:polycytidylic acid-induced deficits in retention and attenuated the increase in body temperature. These results demonstrate that polyinosinic:polycytidylic acid induces memory processing deficits and is pyrogenic in the day-old chick and that these effects are cyclooxygenase-dependent.

This series of studies used a weakly trained (20% methyl anthranilate) version of the passive avoidance learning task in the 1-day-old chick to investigate memory facilitation effects by diphenylhydantoin (DPH). The results indicated that the pairing of the weak training experience with DPH results in facilitation of memory that can be observed from 40 min following training with the weak training experience. The results from a biochemical experiment indicated that DPH facilitates the activity of Na(+)/K(+)-ATPase at the majority of times sampled in a large percentage of the sections of the chick brain. The most marked level of elevation in the activity of the enzyme was observed at the 20-min time point following weak training in the section of the chick brain, which contained several memory relevant neuroanatomical loci. This represents a 68% increase in the activity of the enzyme in those areas considered to be crucial to the processing of memory in the paradigm at a time predicted by previous investigation to be crucial in the development of the intermediate-term memory stage of memory. The results of this series of studies support the notion that Na(+)/K(+)-ATPase plays an important role in memory processing following passive avoidance training in the 1-day-old chick.

This series of studies provides a behavioural account of dopamine D1-receptor-dependent facilitation and disruption of memory for the single-trial passive avoidance task in the day-old chick. The D1 antagonist, SCH23390, induced memory disruption in a dose-dependent manner from 60 min after training with a strong (100% methyl anthranilate) aversant experience. The D1 agonist, SKF38393, was found to facilitate memory in chicks given a weak (20% vol/vol methyl anthranilate) training experience. The D2 antagonist, sulpiride, and the D2 agonist, quinpirole, showed no memory effects. The research indicates an important role for dopamine D1-dependent mechanisms in memory formation in the chick.

We have recently shown that activation of the immune system with lipopolysaccharide (LPS) results in memory-processing deficits for the passive avoidance learning task in the day-old chick. The current study examined two important issues in understanding the mechanisms underlying these memory deficits associated with immune system activation, namely, whether LPS (1) impairs Na(+)/K(+)-ATPase functioning and (2) increases corticosterone (CORT) concentrations in chicks trained on the task. As the effects of LPS on sickness behavior have only previously been characterized in older chickens, this study also tested whether LPS is able to produce similar alterations in day-old chicks. LPS decreased brain Na(+)/K(+)-ATPase activity and increased plasma concentrations of CORT in chicks trained on the passive avoidance learning task. These findings give an insight into some of the mechanisms that may be responsible for the LPS-induced memory-processing deficits. Consistent with previous research in older chickens, LPS increased body temperature in a dose-dependent manner, however, only the lowest dose of LPS tested significantly decreased food intake in the day-old chicks.

The single-trial passive avoidance task is a useful procedure for examining learning and memory in the young chick. However, it has recently been suggested that discrepant results reported by different laboratories are due to differences in training procedure. The present study investigated a number of parameters surrounding the passive avoidance task, using day-old White Leghorn, Black Australorp cockerels. The results suggested that presentation of a water-dipped bead immediately after the aversive bead significantly altered retention levels. In addition, when the water-dipped bead was presented after the aversive bead, chicks failed to discriminate between beads for a period of 10 min following exposure to the aversant experience. A novel variant of the passive avoidance procedure, involving pretraining with a water-dipped red bead, training with an aversant-coated red bead, and testing with a dry red bead, was evaluated. A measure of avoidance was calculated using all three trials. It is suggested that the use of a single bead, measured both before and after the training experience and using both aversant- and water-trained controls, results in the most concise characterization of memory-related phenomena in the chick which is not contaminated by a carryover effect from the aversive training experience to the nonaversive bead.

Recent examination of the mixed dopamine agonist apomorphine suggests that dopamine inhibits both passive avoidance and response suppression learning. The present study investigated the effects of selective dopamine agonists on memory consolidation using a passive avoidance task in the day-old chick. The dopamine D1 agonist SKF 38393, the D2 agonist quinpirole, and the D4 agonist PD 168077 all failed to disrupt memory consolidation when injected immediately after training. However, chicks injected with 6.0 mg/kg of the D3 agonist (+)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) displayed memory impairment 180 min after aversive training. A study of the time course of this effect of 7-OH-DPAT showed that it first appeared 90 min after aversive training. Pretreatment with the dopamine D3 antagonist U 99194 eliminated the disturbance of passive avoidance learning induced by 7-OH-DPAT. These results indicate that dopamine is involved in the later stages of the memory formation process and that the D3 receptor is crucially involved in this disruption.

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.

The discrepant results noted by the La Trobe/Monash, Sussex, Open, and Berkeley University memory research groups employing the passive avoidance task (PAT) with the chick indicate that some of these differences may be due to differences in training procedures between the various groups. The procedures employed by each group were replicated as closely as possible and compared using the same strain of chick. Higher levels of pecking and lower training latencies were observed in the La Trobe/Monash chicks. Improved training latency was observed following a change in the day of experimentation with Sussex chicks, and in white light in Open chicks. A powerful reinforcing effect was observed when pretraining was conducted with a wet lure across multiple pretraining trials, indicating the importance of this difference between groups. The observed impact on chick performance of these variables indicates that differences between PAT procedures may have important interactive effects with aversive learning. The results of data gathered using different procedures may only be superficially comparable, and further investigation of the effects of these variables is indicated., (Copyright 2001 Academic Press.)

The results of this series of experiments with chicks trained on a single trial, passive avoidance task, demonstrate that methotrexate-induced folate deficiency, and excess levels of folate and B12 lead to amnesia in these subjects. The amnesia appears only after 50 min following learning, leaving the earlier processing stages of memory formation unaffected. The application of methotrexate resulted in disruption of righting reflex in a dose dependent manner, however the ataxia did not appear to be the cause of the memory deficit. The deficit in memory induced by methotrexate-induced folate deficiency could be ameliorated with methionine. These studies suggest that cellular processes involving folate metabolism may play an important role in the memory formation of the young chick and that the observed disruption of memory may well occur due to its affect on protein synthesis mediated by alterations in methionine metabolism.

Studies with neonate chicks, trained on a passive avoidance task, suggest that at least two shorter-term memory stages precede long-term, protein synthesis-dependent memory consolidation. Posttetanic neuronal hyperpolarization arising from two distinct mechanisms is postulated to underlie formation of these two early memory stages. Maintenance of the second of these stages may involve a prolonged period of hyperpolarization brought about by phosphorylation of particular proteins. A triggering mechanism for long-term consolidation is postulated to occur at a specific time during the second stage, and may involve reinforcement-contingent release of neuronal noradrenaline stimulating cAMP-dependent intracellular processes. The possibility that astroglia may have a critical role to play in these early stages of memory processing is raised.

Day-old chicks given a single weakly reinforced (20% v/v methyl anthranilate in absolute ethanol) passive avoidance learning trial showed no evidence of long-term memory. A second learning trial given at 15 minutes after initial resulted in consolidation of the learning experience into long-term memory. The retention function resulting from two learning trials is similar to that observed with a single strongly reinforced learning trial, and consists of the stages postulated by Gibbs and Ng. With a dilution of 10% methyl anthranilate in ethanol, four training trials were needed to yield unequivocal evidence of long-term memory consolidation.

Day-old chicks trained on a single-trail passive avoidance learning task, with varying concentrations of the aversive stimulus (methyl anthranilate), truncated retention functions for low concentrations. The retention function for a 20% v/v dilution of methyl anthranilate in absolute ethanol yielded high retention levels until approximately 40 to 45 minutes following learning. This retention function appears to consist of only the short-term and intermediate (phase A) memory stages of Gibbs and Ng's three-stage model of memory formation, with the short-term stage susceptible to inhibition by monosodium glutamate, and the intermediate stage by ouabain and dinitrophenol. The results suggest that processing of memory into the relatively permanent long-term stage may depend on the strength of the reinforcer in aversive learning.