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M E Gibbs

Publications and source records attributed to M E Gibbs.

At least 37 records · Page 2Linked to original sources
PubMed1996

Inhibition of glutamine synthetase activity prevents memory consolidation.

Methionine sulfoximine, a specific inhibitor of the exclusively glial enzyme glutamine synthetase, was shown, at a concentration of 3.5-4.5 mM, to prevent consolidation of memory for a passive avoidance task in day-old chicks. Provided the drug was administered 5-20 min before the learning task, significant retention loss was observed from the normal time of onset of the second of three postulated stages in the memory formation sequence but the drug had to be administered considerably earlier. The amnestic effect of methionine sulfoximine was successfully counteracted by L-glutamine (10 mM) and monosodium glutamate (4 mM), and also by a cocktail of alpha-ketoglutarate (5 mM) and alanine (5 mM). This effect of methionine sulfoximine is attributed to its blockade of the production of glutamine via the glutamate-glutamine cycle, leading to a reduced capacity of neurons to replenish their transmitter glutamate.

Alanine↗
PubMed1995

Inhibitors of cAMP-dependent protein kinase impair long-term memory formation in day-old chicks.

There is substantial evidence that protein kinases, through the phosphorylation of substrate proteins, play a significant role in information processing in the brain, including processes underlying memory formation. Inhibition of the activity of the cyclic-adenosine monophosphate-dependent protein kinase A by the highly specific inhibitor, halofantrine, resulted in impairment of memory formation in day-old chicks trained on a single-trial passive avoidance task. A dose of 9.6 ng/chick halofantrine induced amnesia at the beginning of a protein synthesis-dependent long-term memory stage, the last of three stages of memory postulated to underly memory formation in the chick following passive avoidance learning. The concentration of halofantrine required for 50% inhibition of chick brain protein kinase A was found to be similar to that observed for bovine heart and rat liver. The amnestic effect of halofantrine is tentatively attributed to interference with de novo protein synthesis necessary for long-term memory consolidation. Neither anthraquinone nor the anthraquinone derivative anthraflavic acid, which have little effect on protein kinase A activity, affected memory retention. On the other hand, two other anthraquinone derivatives, chrysophanic acid and purpurin, which inhibit PKA activity, at doses of 0.25 and 0.5 ng/chick also yielded retention deficits. In these cases, however, retention losses occurred earlier than observed with halofantrine, at about 30 min post-training. The earlier effects of these inhibitors may be due to the additional inhibitory action of these compounds on protein kinase C activity, which has been demonstrated in previous studies to be implicated, possibly through phosphorylation of the GAP43 phosphoprotein, in memory processing in the stage of memory immediately preceding the protein synthesis-dependent long-term stage.

Animals↗
PubMed1994

Astrocytic glycogenolysis energizes memory processes in neonate chicks.

In previous pharmaco-behavioural experiments, we have shown that three sequential stages can be distinguished in discrimination memory for a single trial passive avoidance experience in neonate chicks: a short-term (STM) stage, available for 10 min following learning; an intermediate (ITM) stage, operating between 20 and 50 min (ITMB) post-learning; and a long-term (LTM) stage formed by 60 min after learning. The ITM stage can be divided into two parts: a first phase (ITMA) which is susceptible to inhibition by the uncoupler of oxidative phosphorylation (and thus of oxidative metabolism), 2,4-dinitrophenol (DNP), and a second DNP-insensitive phase (ITMB). ITMA occurs between 20 and 30 min post-training and ITMB between 30 and 50 min. In the present study we have shown: (1) that day-old chicks trained in the passive avoidance task and immediately thereafter injected with the glycolytic inhibitor iodoacetate show retention deficits that are first evident 30 min post-training, and (2) that glycogenolysis, i.e. breakdown of glycogen, a high-molecular carbohydrate energy store localized in astrocytes, occurs in the forebrains of trained, but otherwise untreated birds, between 35 and 55 min after learning. These findings strongly suggest that glycolysis, including astrocytically localized glycogenolysis, is essential to provide energy for active processes occurring during ITMB and that these processes are indispensable for subsequent development of long-term memory.

2,4-Dinitrophenol↗
PubMed1994

Effect of PKC inhibitors and activators on memory.

Changes in the activity of the enzyme protein kinase C (PKC) have been implicated in learning and memory consolidation, and in the induction of long-term potentiation. The precise role of PKC in memory processing is still unknown. Using 1-day-old chicks trained on a single-trial passive avoidance task, we demonstrate that inhibition of PKC activity by melittin induced retention loss, in a dose-dependent manner, in the second stage of a three-stage sequence of memory processing. The effect was lateralized to the left hemisphere of the chick forebrain. This effect of melittin was prevented by high concentrations (16-320 microM) of the PKC activator, phorbol 12-myristate 13-acetate (PMA). Furthermore, concentrations of PMA in the range 1.6 to 40 microM were shown to induce long-term memory consolidation following a weakly reinforced version of the learning task, which normally does not lead to formation of long-term memory. That these actions of PMA are attributable to PKC activation is supported by the further finding that the inactive phorbol ester 4 alpha-PDD had no effect either on melittin-induced amnesia or on memory consolidation following weakly reinforced learning. Paradoxically, concentrations of 16 microM or higher of PMA inhibited memory consolidation for the normal strongly reinforced learning trial, an effect again not observed with 40 alpha-PDD. The results are consistent with the view that PKC activity may be implicated in a pre-long-term stage of memory processing.

Animals↗
PubMed1994

Astrocytes implicated in the energizing of intermediate memory processes in neonate chicks.

Day-old chicks trained in a single trial passive avoidance task develop three sequentially dependent stages of discrimination memory. The second intermediate stage is made up of two phases: the initial A phase being susceptible to inhibition of oxidative metabolism in the tricarboxcylic acid (TCA) system with 2,4-dinitrophenol (DNP), and a second DNP-insensitive B phase. The studies reported in this paper found that doses of the metabolic toxins fluoroacetate (0.2 mM) and fluorocitrate (0.1 mM) previously reported to disrupt the astrocytic TCA cycle only, also disrupt the A (but not the B) phase of intermediate memory, suggesting an interaction between the astrocytic and neuronal oxidative systems may be required to meet the metabolic demands of this earlier phase. The B phase, on the other hand, was not expressed in the presence of the glycolytic inhibitor iodoacetate (1 mM), suggesting that glycolysis (known to be more efficient in astrocytes) and glycogenolysis (which may be exclusive to astrocytes) may support this second phase of intermediate memory. In this regard, the rise in forebrain noradrenaline levels previously reported to occur before the appearance of the B phase is particularly relevant. Given that noradrenaline has been shown to be capable of enhancing glycogenolysis in astrocyte-enriched cell cultures, it is conceivable that noradrenaline exerts an effect on memory by stimulating the glycolytic system in astrocytes, thereby providing energy or metabolites (e.g. pyruvate) needed to sustain the cellular processes operating during the B phase of intermediate memory.

Animals↗
PubMed1994

Both non-NMDA and NMDA glutamate receptors are necessary for memory consolidation in the day-old chick.

Day-old chicks (black Australorp-white Leghorn) trained to avoid an aversive stimulus will usually retain memory for this event indefinitely. The passive avoidance task used involves a period of pretraining where chicks peck freely at two differently colored glass beads, a single training trial where one of the beads is coated in a chemical aversant eliciting typical disgust reactions from the chicks, and a test trial where both beads are presented dry, and discrimination memory is demonstrated by avoidance of the previously aversive bead with continued pecking of the nonaversive bead. Intracranial administration of a N-methyl-D-aspartate glutamate receptor antagonist (50 microM 2-amino-5-phosphopentanoate) immediately after or prior to learning, or a non-N-methyl-D-aspartate glutamate receptor antagonist (100 microM 6,7-dinitro-quinoxaline-2,3-dione) between 10 and 25 min after learning, resulted in amnesia for this task at 80 to 90 min post-training. These data indicate that processes dependent on N-methyl-D-aspartate and non-N-methyl-D-aspartate glutamate receptor activation are necessary for memory consolidation of a passive avoidance task in the day-old chick. Since these agents must be administered during the earlier stages of memory formation to cause amnesia, the receptors are probably activated close to the time of learning. The delayed effect of these antagonists, however, suggests that memory is independent of these receptors until quite late in the memory consolidation process.

2-Amino-5-phosphonovalerate↗
PubMed1994

A nitric oxide agonist stimulates consolidation of long-term memory in the 1-day-old chick.

Chicks, age 1 to 2 days, that have been trained on a passive avoidance task with a strongly reinforced training trial yield a memory trace that is composed of 3 behaviorally and pharmacologically distinguishable stages, with the final long-term memory stage being dependent on protein synthesis. In contrast, chicks trained with a weakly reinforced learning trial typically do not demonstrate this final stage of memory. Sodium nitroprusside 150 microM intracranially administered immediately after a weak training trial promoted the formation of long-term memory, whereas saline did not. The results suggest that nitric oxide synthesis is either itself critical or stimulates other processes that are critical for the consolidation of long-term memory.

Age Factors↗
PubMed1991

Behavioral and pharmacological unravelling of memory formation.

A brief description of how a passive avoidance task, using one day-old chicks, has been used to test for memory formation is given. Chicks will peck at bright shiny beads but if a bead is painted with a bitter tasting chemical, after tasting it once, the chicks will refuse to peck on subsequent presentation of that bead. The chick associates the bitter taste with the particular characteristics of the bead. These experiments have led to the development of a model of memory. The basic model is made of short-term memory, which lasts 10 minutes, intermediate memory that has two phases A and B and lasts for 30 minutes and finally long-term memory. The use of certain classes of drugs to prolong, delay or abolish the various phases is described and then it is shown that many hormones and certain behavioral manipulations can modulate memory. Experiments are described which examine not only the temporal storage but delineate spatial storage within the brain. A brief discussion of current methodologies for looking at the exact spatial location of memory traces is given. The article concludes by emphasizing how even minor differences in protocols across laboratories can have large effects on the memory traces and stresses the significance of the narrow temporal windows, around the training trial, when memory can be modulated.

Animals↗
PubMed1991

Molecular mechanisms of memory formation.

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.

Animals↗
PubMed1991

Brain metabolic activity associated with long-term memory consolidation.

The use of day-old chickens trained on a single-trial passive avoidance task provides a useful paradigm for investigations into cellular mechanisms underlying memory formation. Pharmacological intervention studies indicate that there are three temporally identifiable stages of memory processing leading to the consolidation of information for this task. These stages, designated as short-term (STM; up to 15 min), intermediate-term (ITM; 15-55 min), and long-term (LTM; more than 55 min) memory, have been found to be sequentially dependent (Ng and Gibbs, 1989). In addition, ITM appears to consist of two physiologically distinguishable phases, A and B. Evidence in this laboratory suggests that the crossover between these ITM phases (at 30 min after training) represents a critical time-point for the triggering of LTM.

Animals↗
PubMed1991

Possible noradrenergic involvement in training stimulus intensity.

Day-old chicks trained on a single trial passive discrimination avoidance task using a concentrated chemical aversant, methyl anthranilate (MeA), have been shown to exhibit three stages of memory processing: short, intermediate and long term. A similar learning task with the aversant diluted to 20% in ethanol leads to short- and intermediate-term memory only, but not to long-term memory. The emergence of long-term memory has been shown to be associated with the production of a nonenergy-dependent phase of the intermediate memory stage. Subcutaneous administration of propranolol proved capable of inhibiting this nonenergy-dependent phase of memory under a number of training regimes: strongly reinforced training, and with weakly reinforced training presented twice or coupled with a selected dose of the stress-related hormone ACTH. This study supports the notion that there is a phase of memory that occurs prior to the protein synthesis-dependent phase of memory which is susceptible to interference by drugs affecting noradrenergic processes and which may be associated with the intensity of the training stimulus.

Animals↗
PubMed1991

Forebrain noradrenaline concentration following weakly reinforced training.

Day-old chicks trained on a single-trial discriminated passive avoidance task using a concentrated taste aversant, methyl anthranilate, have been shown to exhibit three stages of memory processing; short-, intermediate-, and long-term memory. If the aversant is diluted to 20% v/v methyl anthranilate in absolute ethanol, only the short-term and some of the intermediate stage are observed. In this study we investigated the whole forebrain levels of noradrenaline in response to differing intensities of the training experience. The results show a profound difference in the level of whole forebrain NA at all training-sacrifice intervals for the trained as compared to the untrained controls, except at 15- and 20-minute posttraining, when a substantial reduction in the level of NA was achieved under all training conditions. Furthermore, subjects which received treatments which resulted in the emergence of behavioural evidence of long-term memory tended to have higher levels of whole-forebrain NA at 30 minutes after initial training. This is the time when we have postulated that triggering of protein synthesis associated with long-term memory formation takes place.

Animals↗
PubMed1990

Memory consolidation of weak training experiences by hormonal treatments.

Day-old chicks trained on a single-trial passive discrimination avoidance task using a concentrated chemical aversant, methyl anthranilate (MeA), have been shown to exhibit three stages of memory processing; short-, intermediate- and long-term. A similar learning task with the aversant diluted to 20% in ethanol leads to short-and intermediate-term memory, but no long-term memory. Subcutaneous administration of selected doses of the stress-related hormones, noradrenaline, ACTH and vasopressin in close temporal proximity to the training trial, produced long-term memory in chicks trained on the weakly reinforced task, mimicking the outcome of strongly reinforced learning and of retraining with the weakly reinforced task reported previously. These effects are shown to be associated with the production of a nonenergy-dependent phase of the intermediate memory stage, postulated to be necessary for long-term memory consolidation.

2,4-Dinitrophenol↗
PubMed1989

Memory formation processes in weakly reinforced learning.

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.

2,4-Dinitrophenol↗
PubMed1989

Effect of retraining trials on memory consolidation in weakly reinforced learning.

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.

2,4-Dinitrophenol↗
PubMed1987

Inhibition of memory in the chick using a monoclonal anti-Thy-1 antibody.

One-day-old chicks trained on a single trial passive avoidance task were administered a monoclonal anti-chick Thy-1 antibody, either intracranially or subcutaneously, at various times before and after learning and retention tested at various times post-learning. This procedure resulted in profound amnesia when anti-Thy-1 antibody was administered immediately before learning (5 min) in the case of the subcutaneous injections or 5 min before until 5 min after the learning process with intracranial injections. Antibody administered at other times, either before or after learning had little or no effect on retention. Retention levels were normal until 50 min post-learning, then declined sharply and remained at control levels for the duration of the test period. Chicks injected with anti-chick cerebellum or anti-rat Thy-1 antibodies showed no evidence of amnesia for the concentration of the antibodies used.

Animals↗
PubMed1987

Effect of excess intracranial amino acids on memory: a behavioural survey.

Nineteen naturally occurring amino acids were administered intracranially to day-old chicks at various times before and after a single trial passive avoidance learning task. The results suggest a consistent and simple difference between essential and non-essential amino acids. Except for arginine, phenylalanine, tryptophan and tyrosine, the essential amino acids had no effect on memory formation when administered 5 min before or immediately after learning. However, arginine, phenylalanine and tryptophan yielded amnesia after 60 min following learning, when given between 5 min before and 2.5 min after learning. In the case of tryptophan, amnesia was only temporary, lasting from 60 min to 240 min post-learning. All non-essential amino acids, when administered between 5 min before and 5 min after learning yielded amnesia by 60 min post-learning, with no evidence of recovery by 24 hr post-learning. Alanine-, asparagine-, cysteine- and glutamate-treated chicks, however, showed signs of generalized avoidance shortly after administration. The retention time courses after injection of glutamine, proline, serine and taurine were similar to that obtained with the non-metabolizable amino acid alpha-amino-isobutyric acid, and amnesia arising from administration of these amino acids was counteracted by diphenylhydantoin, as was amnesia induced by phenylalanine and tyrosine. The retention function obtained with tryptophan was similar to that obtained with 5-hydroxytryptamine, and DPH had no effect on the action of tryptophan or the actions of arginine, alanine or asparagine. The findings were interpreted in the context of a three-stage model of memory formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗