One-trial Passive Avoidance Learning Task Research Articles

The effects of morphine at different embryonic ages on memory consolidation and rewarding properties of morphine in day-old chicks

Prenatal exposure to morphine can alter the capacities for learning and memory and the sensitivity to drugs of abuse in progeny. In the present study, we examined the effects of morphine during chick embryonic period of 5–8, 9–12, 13–16 and 17–20 on cognitive function and the sensitivities to morphine reward in the post-hatch chick, using the one-trial passive avoidance learning task and the conditioned place preference paradigm. It was observed that the injection of morphine (1 mg/kg of egg weight) during E5–8, but not in other three periods, significantly impaired intermediate- and long-term memory in one-day-old chicks. On the other hand, the chicks prenatally exposed to morphine during E17–20 remarkably not only acquired but also maintained the conditioned place preference induced by morphine. The present results suggest that there are two time-windows during development, which in the chick are around E5–8 and E17–20, when prenatal morphine exposure is likely to confer maximal risks for vulnerabilities to breakdown of memory consolidation and to morphine-induced reward in day-old chicks respectively.

Chronic prenatal lead exposure impairs long-term memory in day old chicks

Environmental exposure to lead during developmental stages has been established as a potential cause of intellectual deficits. The high susceptibility of rapidly developing fetal and infant brains to external factors suggests that impairment of later cognitive functions may arise from relatively minor prenatal exposure to environmental lead levels. In this study, we used the one-trial passive avoidance learning paradigm with day old chicks to evaluate memory function and memory consolidation in response to prenatal lead exposure. Lead acetate (5.5mg/kg, 11mg/kg, 16.5mg/kg) was administered daily from E9 to E16 via direct injection into the airspace in chick eggs. Higher doses of lead acetate (11mg/kg, 16.5mg/kg) administration had significant effects on the hatching success (23.4 and 17, respectively) and hatch weight ( approximately 10% decrease) of chicks when compared to equivalent treatments of sodium acetate (11mg/kg, 16.5mg/kg) (p<0.001). Low doses of lead acetate (5.5mg/kg) did not significantly affect chick hatching, weight or morphology compared to equivalent sodium acetate treatments (5.5mg/kg) and controls. However, lead acetate (5.5mg/kg) was found to significantly impair long-term memory after 120min following training in the one-trial passive avoidance learning task (p<0.05). These findings add to a growing body of evidence that suggests lead toxicity during fetal development leads to impairment in cognitive and memory processes.

Effects of Lanthanum Chloride Administration in Prenatal Stage on One-Trial Passive Avoidance Learning in Chicks

Lanthanum cations (La 3+) are well known for their inhibitory actions on calcium channels. Prenatal lanthanum exposure may affect the development of embryo and alter the capacity for learning and memory in adults, and the one-trial passive avoidance learning paradigm with day-old chicks is an excellent model to study several mechanisms of memory formation. In the present study, we examined the effects of prenatal lanthanum chloride exposure on memory consolidation using one-trial passive avoidance learning task in day-old chicks. The data suggest that chicks injected with lanthanum chloride (2 mg/kg) daily from E9 to E16 had significantly impaired long-term memory at 120 min after training (p < 0.05) but not the chicks injected with lanthanum chloride (0.1 mg/kg) daily from E9 to E16.

Aposematic colouration enhances memory formation in domestic chicks trained in a weak passive avoidance learning paradigm

The one-trial passive avoidance learning task is commonly used in avian research to explore anatomical, cellular and molecular parameters of learning and memory. Many factors are known to influence the effectiveness and/or duration of such learning events. Combinations of novel odours, such as pyrazine, and aposematic colours, such as brig ht yellow or red, have been shown to induce a long-lasting aversion to food crumbs in ‘visual’ predators, including birds such as the domestic chick (1). The aim of this study was to (a) examine whether visual complexity played a role in the generation of an aversive response to a novel visual stimulus and (b) to establish whether the duration of memory of an aversive experience could be modified by altering the visual properties of the stimulus. In the first experiment, naïve domestic chicks were trained on a weakly aversive one-trial passive avoidance bead task, in which chicks were allowed to peck at a bead coated with a 10% solution of the bitter-tasting and odorous substance methylanthranilate (MeA). The chicks were trained with (allowed to peck) one of four differently coloured beads dipped in 10% MeA. Chrome, black, yellow or black-and-yellow striped beads were used. ‘Recall’ of the aversive bead was examined by presenting the (clean) training bead 24 h after training and monitoring avoidance to it compared to a ‘neutral’ white bead. A high proportion (63%) of chicks trained with the black and yellow striped bead avoided it 24 h after training, whereas little or no avoidance was seen in response to chrome, yellow or black beads. In a second experiment naïve domestic chicks were all trained once only with a black and yellow striped bead coated in a 10% MeA solution, but this time, were tested 24 h later, once only, with either a black, a yellow or a black and yellow striped bead. Nearly 60% of chicks tested with a black and yellow striped bead showed avoidance of the bead, whereas only 23% of those tested with a black bead and 14% tested with a yellow bead showed avoidance. These results confirm the importance of complex warning colouration, when paired with a novel olfactory cue and a bitter taste, in avoidance learning. We conclude that the chicks’ response to monochromatic colours (e.g. yellow or black) is not affected by their previous experience with a conspicuously patterned stimulus (yellow and black stripes). Moreover, it suggests a predisposition for chicks to attend to aversive cues associated with ‘naturalistic’ high contrast colour cue combinations such as black and yellow.

Memory beyond the synapse

Based on studies of the molecular and cellular cascades that occur during memory consolidation for a one-trial passive-avoidance learning task in the young chick, I review the evidence that memory is encoded in permanent changes in synaptic connectivity ina specific brain region, the Hebb hypothesis. I conclude that despite the fact that such a cascade occurs, culminating in the synthesis of cell-adhesion molecules that are involved in synaptic remodelling, synaptic events are not in themselves sufficient to account for the phenomena of memory. Both whole brain (neuromodulator) and whole body (hormonal) processes are engaged.Memories are labile, disarticulated and stored in a distributed manner; how the mind/brain recreates coherent memories from this pattern is a mystery.

Metabotropic glutamate receptors (mGluRs) are involved in early phase of memory formation: possible role of modulation of glutamate release

Metabotropic glutamate receptors (mGluRs) groups I and II are involved in the cellular processes of long-term potentiation (LTP) and learning and memory formation. I.c.v. injection of the mGluRs agonist 1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) can impair memory formation in some types of learning task. The role of mGluRs in neurotransmitters release and production of second messengers has been suggested. The aim of the present study was to determine the effect of i.c.v. administration of the new potent mGluRs agonist ABHxD-I and compare its effect with that of ACPD. We studied the effect of both agonists on acquisition and memory for a one-trial passive avoidance learning task in day-old chicks and on the training related glutamate (Glu) release. ACPD or ABHxD-I (50nmole per chick, i.c.v. injection) were administered at different times before or after training and chicks were tested at various times after training. Chicks injected with ABHxD-I 30min before training showed amnesia when tested 30min or 3h after training. The amnestic effect of ACPD was significant only 30min after training. Glu release evoked by 70mM KCl was measured in slices prepared from the IMHV of chick brain isolated from animals injected with either ACPD or ABHxD-I 30min before training and tested 30min after training. Glu concentration was measured using HPLC. Both ACPD and ABHxD-I significantly increased Glu release in slices isolated from untrained chicks (30 and 48% compare to control, respectively, P<0.05). Training itself increased Glu release (41% compared to control, P<0.01) and no additional effect of either ACPD or ABHxD-I was observed. These results suggest that mGluRs groups I and II are involved in the early stages of memory formation and that application of either of the studied mGluRs agonists may interfere with that process. The amnestic effect of ABHxD-I seems to be stronger and longer lasting. Although the mechanism of this effect still remains unclear, our results suggest that disregulation of Glu release by mGluR agonists may participate in this process.

Comparison of methyl anthranilate and denatonium benzoate as aversants for learning in chicks

Methyl anthranilate (MeA) has been widely used as a taste aversant for domestic chicks in the one-trial passive avoidance learning (PAL) task. However, MeA has a strong smell that may be aversive to chicks. Therefore, odourless denatonium benzoate (DB) has been suggested as an alternative taste aversant in PAL. The present study was designed to compare the efficacy of MeA and DB as aversants in the one-trial PAL task. In this task, young chicks peck a visually conspicuous bead coated with a taste aversant and in a single trial learn to avoid a similar, but uncoated bead at subsequent presentation. In Experiment 1, chicks were trained using a silver-coloured bead coated with 100% MeA, 0.5% DB or distilled water. After 3 h, MeA-trained, but not DB-trained chicks, exhibited significantly higher avoidance of the test bead than water-trained chicks. In Experiment 2, three pre-training presentations of an uncoated red bead preceded training with the silver bead. MeA-trained chicks showed significantly higher avoidance of the test bead than water-trained chicks. The numbers of water- and DB-trained chicks that avoided pecking the test bead were low and not significantly different from each other. However, DB-trained chicks exhibited significantly longer latencies to peck the test bead than water-trained chicks, indicating that they had retained some memory of the task. Thus, 0.5% DB is a weaker aversant than MeA and it does not induce high levels of learning in the one-trial PAL task. However, DB may prove useful for investigating weakly reinforced learning.

Role of brain-derived neurotrophic factor and presynaptic proteins in passive avoidance learning in day-old domestic chicks

The consolidation of a one-trial passive avoidance learning task in the day-old chick involves a number of transient and longer-term biochemical processes, including increased release of glutamate. This study demonstrated that brain-derived neurotrophic factor, a proposed modulator of synaptic transmission and neurotransmitter release, is involved in the cascade associated with memory consolidation in the chick and that its actions were linked to modulation of expression of SNAP-25, syntaxin and synaptophysin, required for exocytosis. Intracerebral injections of 5 μl of antibodies to brain-derived neurotrophic factor into the left and right intermediate medial hyperstriatum ventrale resulted in a dose-dependent reduction in avoidance of an “aversive” bead by 3 h after training. Neurotrophin antibodies (0.5 μg/chick) administered between 1 h before, and up to 30 min after, training induced amnesia by 3 h which was sustained for at least 24 h. Injections of recombinant brain-derived neurotrophic factor (50 μg/ml; 0.5 μg/chick) just before training maintained avoidance in birds trained with a weaker aversant (10% methylanthranilate), such that chicks showed enhanced recall at times (24 h) beyond that when shorter-term forms of memory have decayed. In lysed synaptosomal membranes prepared from chicks injected with antibodies to brain-derived neurotrophic factor there was a decrease in expression of SNAP-25 and syntaxin in the left, but not the right, intermediate medial hyperstriatum ventrale, a region known to be associated with memory formation, which correlated with the decrease in neurotrophin concentration. Thus, these data indicate that brain-derived neurotrophic factor is involved in the formation of a long-term memory for an aversive stimulus and may function as a modulator of presynaptic proteins associated with exocytosis, enabling increases in neurotransmitter release.

Characterisation and regional localisation of pre- and postsynaptic glycoproteins of the chick forebrain showing changed fucose incorporation following passive avoidance training.

To identify those glycoproteins whose synthesis or modification is necessary for memory formation, we have studied the uptake of radiolabelled fucose into synaptic plasma membranes (SPMs) and postsynaptic densities (PSDs) derived from two specific left and right forebrain loci, at two different times after training of 1-day-old chicks on a one-trial passive avoidance learning task. To increase the reliability of the comparison, a double-labelling method was used. Tissue samples from intermediate medial hyperstriatum ventrale (IMHV) and lobus parolfactorius (LPO) were isolated at 6 and 24 h after training. At both times, training resulted in region-specific changes, both increases and decreases, in incorporated radioactivity into pre- and postsynaptic glycoproteins. After 6 h, there was a relative decline in incorporation into both SPMs and PSDs of the right IMHV of trained chicks, a decline that persisted in the PSDs until 24 h. A small decline in incorporation in SPMs from the right LPO of trained chicks at 6 h was reversed by 24 h, by which time there was a 64% increase in incorporation into SPMs and a 24% increase into PSDs of the left LPO. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis of left and right hemisphere samples containing LPO revealed that 6 h after training the main effect was presynaptic, including a reduction of incorporation into high molecular mass glycoproteins, of 150-180 kDa, and an increase in a lower molecular mass (41 kDa) fraction. By 24 h after training, a left hemisphere presynaptic glycoprotein of molecular mass approximately 50 kDa showed the biggest increase in fucosylation. In addition, a wide group of postsynaptic glycoproteins of both hemispheres, in the ranges 150-180, 100-120, and 33 kDa now showed increases in incorporation. Some other fractions showed decreases. These results are in accord with previous data on incorporation obtained using the amnesic agent 2-deoxygalactose. They also support the hypothesis that memory formation involves the strengthening of connections between pre- and postsynaptic neurons of the LPO by growth or modulation of pre- and postsynaptic structures.

Diphenylhydantoin facilitation of labile, protein-independent memory

Diphenylhydantoin (DPH 10 −4M) administered subcutaneously to chicks 5 min after a one-trial passive avoidance learning task successfully counteracted anmesia induced by pretreatment 5 min before learning with ouabain or cycloheximide (CXM). Biochemical assays confirmed that in chick forebrain homogenate DPH at concentrations of 1 and 5 × 10 −4 M enhanced Na +/K + ATP'ase activity. Since both DPH and ouabain inhibit post-tetanic potentiation, the results support the hypothesis of an initial labile phase of memory based on sodium pump (Na +/K + ATP'ase) activity. DPH was less effective in counteracting ouabain-induced amnesia if administered later than 10 min after learning and CXM-induced anmesia if administered later than 30 min after learning. This suggests that the effect of DPH on CXM-induced anmesia is through enhancement of Na +/K + ATP'ase activity. It was suggested that the possible hyperpolarization of membrane potential associated with sodium pump activity may serve to mark the labile memory trace, enabling formation of a more permanent trace through protein synthesis.

Drug inhibition of memory formation in chickens. I. Long-term memory.

1. A one-trial passive avoidance learning task using day-old chickens is described and shown to be suitable for testing the effects of direct intracranial injection of drugs. 2. Inhibitors of the sodium pump have been found to block the formation of long-term memory only if present at the time of learning. 3. Inhibitors of protein synthesis will prevent long-term memory formation even if they are administered after learning. 4. From this, there appear to be at least two stages in the formation of memory. A short-term phase dependent on membrane mechanisms leads to permanent storage dependent on protein synthesis.