Saccharin aversion memory in rats: inhibition of cycloheximide-resistant memory by ouabain.
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Animals↗
Biomedical subjects
M E Gibbs
Publications and source records attributed to M E Gibbs.
Neuronal depolarization and the inhibition of short-term memory formation.
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Animals↗
Biochemical aspects of protein synthesis inhibition by cycloheximide in one or both hemispheres of the chick brain.
Instracrnial administration of cycloheximide into one hemisphere of the chick brain resulted in inhibition of 14C-leucine incorporation into protein only in that hemisphere when the labelled amino acid was administered intracranially. With pericardial injections of labelled amino acid, inhibition of 14C-leucine incorporation was obtained in both the CXM-treated and the untreated hemisphere, when compared with bilateral saline-treated controls. The levels of inhibition were comparable to those obtained with bilateral administration of CXM. There was, however, a slight but significantly higher level of inhibition in the CXM-treated hemisphere. The results were interpreted as supporting the conclusion that monocular learning in chicks resulted in the formation of an engram only in the trained hemisphere.
Animals↗
Similar effects of a monoamine oxidase inhibitor and a sympathomimetic amine on memory formation.
Amnesia resulting from inhibition of cerebral protein synthesis by cycloheximide can be prevented by subcutaneous injection of the monoamine oxidase inhibitor pargyline (25 mg/kg) or the sympathomimetic amine metaraminol (3.0 mg/kg) administered up to 30 min following learning of a single trial passive avoidance task in day-old chickens. The injection has to be made during the life time of labile memory for the prevention of cycloheximide-induced amnesia. On the other hand, amnesia induced by the Na/K ATP'ase inhibitor ouabain can only be prevented if these two agents are administered up to 5 min after learning, i.e. during the life time of short-term memory. In addition, both agents produce a retrieval deficit 90 min after the injection, but only when memory is in long-term storage. These results are compared to those obtained with administration of norepinephrine, d-amphetamine and diphenylhydantoin.
Animals↗
Interhemispheric engram transfer in chick.
Monocular training on a one-trial passive avoidance task in the young chick has been shown to establish an engram in the forebrain hemisphere contralateral to the trained eye, and hence interocular transfer of this task must involve the naive hemisphere making access to the engram in the opposite hemisphere. We have studied the consequences for the untrained hemisphere of accessing a unilateral engram during two short term stages of its consolidation, by conducting interocular transfer tests at 7.5 min and 30 min after learning, prior to onset of amnesia induced by intracranial injection of ouabain or cycloheximide. Testing the naive hemisphere 24 h later indicated that engram transfer had occurred in chicks receiving one access trial at 7.5 min, during the first stage of consolidation of the unilateral engram. At 30 min, during second consolidation stage, five access trials were required to achieve engram transfer. These experiments confirm the findings from the rat that engram transfer can follow from making access to the unilateral engram. However, it has not previously been recognised that interhemispheric memory transfer depends on the recency of formation of the unilateral engram.
Animals↗
Behavioural stages in memory formation.
Day-old chickens trained in pairs on an aversive discrimination task yielded a retention function with two points of reduced retention, at 15 and 55 min after learning. These points of temporary reduction in retention were interpreted as reflecting change-over of recall from three successive phases in memory formation. Chicks trained in isolation showed the same retention function as paired chicks except that the second point of reduced retention occurred at 70 min after learning. It was suggested that isolation prolonged the availability for recall of the second phase of memory formation. The findings are consistent with and support a three phase, behaviourally sequentially dependent, model of memory formation previously postulated on the basis of pharmacological studies.
Animals↗
The influence of calcium on short-term memory.
Using a passive avoidance behavioural task in day-old chickens, it is possible by intracranial injection of appropriate drugs to separate out three phases of memory formation. The duration of the first such phase, called short-term memory, is increased when the intracranial calcium ion concentration is raised and the phase is practically abolished by injection of lanthanum ions.
Animals↗
A possible physiological mechanism for short-term memory.
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Animals↗
Memory formation for an appetitive visual discrimination task in young chicks.
The three-phase model of memory formation in young chicks proposed by Gibbs and Ng [7] was based on a single trial passive avoidance task. Some methodological and interpretative problems associated with this task are not encountered in appetitive visual discrimination tasks. Using such a task, it is shown that 2 mM KCl induces amnesia at 10 min, ouabain at 30 min and cycloheximide at 60 min after learning. These findings are consistent with those for the single trail passive avoidance task and confirm the generality of a model of memory formation in young chicks entailing a short-term phase, a sodium pumo-dependent labile phase, and a long-term, protein synthesis-dependent phase.
Animals↗
Unilateral storage of monocular engram in day-old chick.
Efficient interocular transfer of a one-trial passive avoidance task by the day-old domestic chicken, for whom the optic nerves decussate completely, raised the question of whether memory for the task was held in one or both sides of the forebrain. Intracranial injection of ouabain or cycloheximide to the trained hemisphere immediately after learning suppressed avoidance behaviour learned monocularly, while injection to the untrained side did not. Memory for the task was established in the side of the brain served by the eye used in learning. Interocular transfer was therefore achieved by the untrained hemisphere borrowing information from the other side's store. The presence of memories in the trained side was not sufficient to establish memory in the naive side.
Age Factors↗
Counteractive effects of norepinephrine and amphetamine on quabain-induced amnesia.
Ouabain, administered 5 min prior to learning induces amnesia for a single-trial passive avoidance task in day-old chickens by inhibiting memory formation during the labile sodium-pump dependent phase. Amphetamine and norepinephrine (NE) successfully counteract ouabain-induced amnesia when administered immediately after learning. The actions of these drugs on ouabain-induced amnesia parallel that of diphenylhydantoin (DPH), and within similar time constraints. It is concluded that amphetamine (through release of NE) and norepinephrine exert their effects through stimulation of Na+/K+ ATP'ase activity. This conclusion is supported by the observation that these drugs do not overcome potassium chloride (KCl) inhibition of memory formation in the short-term phase prior to formation of labile sodium-pump dependent memory, and the fact that the noradrenergic blockers, propranolol and piperoxane do not alter the couteractive influence of DPH on cycloheximide (CXM) inhibition of the protein synthesis dependent long term memory phase which follows the labile phase.
Amnesia↗
Cycloheximide and passive avoidance memory in mice: time-response, dose-response and short-term memory.
The greatest loss of memory shown by mice 24 hr after learning was found to occur with cycloheximide (CXM) (120 mg/kg) administered subcutaneously 30 min before training. With injection at this time the extent of the amnesia was dose dependent (30-150 mg/kg) and the resultant amnesia was found to be relatively constant when tested at 1, 7 or 14 days. An attempt was made to follow the development of this amnesia with 100 and 120 mg/kg CXM. However, the saline controls showed an unexpectedly low avoidance 6 hr after training. This was interpreted as a possible interaction between the stress of the injection and the 6 hr interval. An experiment designed to test this possibility showed that mice injected with 0.1 ml of 1% lignocaine gave high avoidance at 6 hr but mice receiving only a needle puncture of the skin gave performances similar to mice receiving saline injections. It was felt that these findings cast doubt on the usefulness of the passive avoidance task in the assessment of drug action on short term memory.
Animals↗
Modulation of cycloheximide-resistant memory by sympathomimetic agents.
Amphetamine overcomes the amnesia caused by cycloheximide (CXM) provided it is administered closely following the learning trial. In day-old chickens with one trial passive avoidance learning, there is a short-term, labile memory existing for 90 min following training under the influence of CXM. Amphetamine has been shown to keep the memory at precisely the level exhibited by the labile, cycloheximide-resistant memory trace at the time of injection. Norepinephrine, methoxamine (an alpha adrenergic stimulant) and isoprenaline (a beta adrenergic stimulant) each mimic the amphetamine effect in CXM-pretreated chickens. That the action of amphetamine could be due to its release of norepinephrine is supported by the finding that it could be blocked by both alpha adrenergic (piperoxane) and beta adrenergic antagonists (propranolol). It has been suggested that this labile memory trace depends on the functioning of a sodium pump. Norepinephrine may be modulating memory formation by an action on the sodium pump since in preliminary biochemical assays norepinephrine stimulated the sodium pump (Na+/K+ ATPase) activity in chicken forebrain total homogenate.
Amphetamine↗
Effects of amphetamine on short-term, protein-independent, memory in day-old chickens.
When the protein synthesis inhibitor cycloheximide (CXM) is administered just before or soon after a single learning trial, the formation of permanent memory is prevented in day-old chickens. In spite of the blockage of long-term memory, which occurs by 3 hr, Mark and Watts [14] have demonstrated a short-term memory which is independent of protein synthesis and which decays over the 3 hr period. D-amphetamine sulphate, administered subcutaneously (up to 2 hr) after learning to CXM pretreated chickens, held the memory at the level exhibited by the labile memory trace at the time of injection. This close relationship between the amount of labile memory and the time of injection was still apparent 24 hr after learning. These data suggest that, provided there is sufficient labile memory in existence at the time of administration, amphetamine maintains the trace which would otherwise decay and allows it subsequent consolidation into permanent memory at a time later than normal.
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Diphenylhydantoin facilitation of labile, protein-independent memory.
Diphenylhydantoin (DPH 10(-4)M) administered subcutaneously to chicks 5 min after a one-trial passive avoidance learning task successfully counteracted amnesia 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 X 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 amnesia if administered later than 30 min after learning. This suggests that the effect of DPH on CXM-induced amnesia 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.
Adenosine Triphosphatases↗
Drug effects on sucessive discrimination learning in young chickens.
Chicks were trained to avoid pecking either a red or a blue bead in a one-trial avoidance task by coating one bead with methy anthranilate. They avoided the aversant bead on retention tests 10 to 180 min or 24 hr after learning, but not the neutral bead. Intracranial administration of ouabain or cycloheximide (CXM) 5 min before learning resulted in decay in retention after 10 and 30 min respectively following learning, discrimination being effective prior to those times. In a second experiment, chicks were trained on three physically distinct beads, two of which were made aversive during the learning period, the training trials separated by an hour. Saline-treated chickens retained memory of both aversive beads on retention trials 180 min later. CXM- and ouabain-treated chickens showed loss of memory for the bead associated with the drug but showed retention of the task which was not associated with the drug.
Animals↗
Sodium pump activity, amino acid transport and long-term memory.
Long-term protein synthesis-dependent memory formation is shown to be inhibited by the non-metabolizable amino acid alpha-amino-isobutyrate (AIB) possibly through a process related to competition for uptake with amino acids necessary for protein synthesis specific to long-term memory. Unlike cycloheximide (CXM) which inhibits long-term memory by inhibiting ribosomal protein synthesis, AIB is non-effective when administered 10 min or more after learning, and its effect is overcome by the sodium pump stimulator diphenylhydantoin if the latter is administered 10 min or more after learning. Within the model of memory formation adopted in this paper it is postulated that the amino acids necessary for long-term memory protein synthesis are taken up by sodium pump activity in the first 10 min following learning, when formation of the preceding labile memory phase is occurring.
Amino Acids↗