Mechanisms of induction and retrieval of latent (hidden) memory for conditioned food aversion were investigated in snails. After initial training (single combination of a food stimulus with electric ...shock), aversive reactions to presentation of the conditioned food stimulus were not revealed. Repeated presentation of the stimuli in 12 days after the first combination was followed by the appearance of aversive food reactions that persisted for at least 14 days. Injections of inhibitors of protein (cycloheximide) or RNA (α-amanitin) synthesis immediately after the first or second combined presentation of the stimuli disturbed skill performance. We hypothesized that single combination of food and reinforcing stimuli led to translation- and transcription-dependent induction of latent conditioned food aversion memory. Transformation of this memory into an active state after repeated presentation of the stimulus combination also depends on the synthesis of new proteins and RNA.
Involvement of neurotransmitter receptors and translation and transcription processes in reconsolidation of conditioned food aversion memory was investigated in experiments on edible snails. ...Injections of neurotransmitter receptor antagonists and protein synthesis inhibitors before the reminder session were found to induce amnesia that was characterized by the possibility of memory recovery in repeated training and under the effect of mnemotropic agent D-cycloserine (early stage of amnesia) or by resistance to the mentioned actions (late stage). It has been shown that amnesia induction by memory reconsolidation impairment by neurotransmitter receptor antagonists depends on synthesis of specific proteins and mRNA, similar to the cases of induction of other adaptive brain modifications.
We studied the role of glutamate receptors and reminder in the mechanisms of amnesia maintenance caused by disruption of conditioned food aversion reconsolidation with an antagonist of NMDA glutamate ...receptor in snails. At the early stage of amnesia (day 3 after induction), injection or NMDA of AMPA glutamate receptor antagonists prior to reminder (presentation of the conditioned food stimulus) led to memory recovery. Reminder alone or injection of antagonists without reminder or after reminder was ineffective. At the late stage of amnesia (day 10), antagonists/reminder had no effect on amnesia maintenance. It was hypothesized that reminder at the early stage of amnesia led to reactivation and reconsolidation of the molecular processes of amnesia including activation NMDA and AMPA glutamate receptors. Injection of antagonists of these receptors prior to reminder led to disruption of reactivation/reconsolidation of amnesia and recovery of the conditioned food aversion memory.
Common snails previously trained to an associative skill consisting of refusing a defined foodstuff were used to study the effects of the ionotropic AMPA-kainate glutamate receptor antagonist DNQX, ...the serotonin receptor antagonist methiothepin, and the protein synthesis inhibitor cycloheximide on long-term memory reconsolidation processes. DNQX and cycloheximide given 24 h after training and before a reminder procedure were found to lead to impairment of the reproduction of the acquired skill, which was not restored by retraining two weeks after initial training. The skill impaired after methiothepin and the reminder recovered on retraining. However, simultaneous injections of DNQX and cycloheximide or methiothepin and cycloheximide before the reminder produced no impairment to the skill. It is suggested that irreversible and reversible types of amnesia induced by AMPA-kainate glutamate receptor antagonists and serotonin antagonists respectively require the synthesis of specific protein molecules.
The specific features of memory reconsolidation in edible snails were studied over 30 days after learning of conditioned food aversion. Injections of a NMDA glutamate receptor antagonist MK-801 or ...protein synthesis inhibitor cycloheximide in combination with the conditioned food stimulus (reminder) on day 2 after learning were followed by the development of amnesia. Repeated training on day 10 after the induction of amnesia did not result in skill formation. Injections of MK-801 or cycloheximide and reminder by the 10th day after training had no effect on memory retention. Injections of MK-801 or cycloheximide and reminder by the 30th day after training were followed by the development of amnesia. In these experiments, memory was recovered after repeated training. Our results indicate that a complex phase reorganization of memory occurs over 30 days after learning. This process includes memory consolidation over the first days after training, stabilization and resistance to adverse factors after 10 days, and newly acquired ability for reconsolidation by the 30th day after training.
1.25 mg/kg) given without a reminder two days after training were ineffective, while ZIP (2.5 mg/kg) evoked transient memory impairment one day after injection with spontaneous recovery on day 10. ...Injections of ZIP (5 mg/kg) without a reminder led to memory impairment and the development of stable amnesia. On repeat training of animals 11 days after induction of amnesia induced by ZIP (5 mg/kg), the number of combined food and reinforcement stimuli required to form the memory was similar to that in initial training. ZIP (5 and 10 mg/kg) combined with a reminder induced amnesia, though repeat training at 11 days led to dose-dependent increases in the rate of formation of memory than on initial training. It is suggested that in snails trained to conditioned food aversion, inhibition of a PKMzeta-like enzyme without a reminder induced “fading of the memory trace,” while repeat training formed a new memory. PKMzeta is evidently not directly involved in the process of memory reconsolidation, though reminding prevented the amnestic effect of ZIP.
We studied the involvement of Mζ-like protein kinase (PKMζ) into mechanisms of conditioned food aversion memory reconsolidation in
Helix lucorum
. Injections PKMζ inhibitor ZIP in a dose of 5 mg/kg ...on day 2 or 10 after learning led to memory impairment and amnesia development. Injections of the inhibitor in doses of 1.5 or 2.5 mg/kg had no effect. Repeated training on day 11 after induction of amnesia resulted in the formation of memory on the same type of food aversion similar to first training. The number of combinations of conditional (food) and reinforcing (electrical shock) stimuli was similar during initial and repeated training. We hypothesize that the inhibition of Mζ-like protein kinase erases the memory trace and a new memory is formed during repeated training.
The dynamics of the reproduction of long-term memory one and five days after acquisition of a spatial memory in a Morris water maze in rats and training to conditioned food aversion in common snails ...were studied. Animals trained for several days demonstrated stable and high levels of reproduction of memory one and five days after training. One-day training of mollusks and rats gave a higher level of reproduction of the memory on day 5 than on day 1. These results suggest that the spontaneous enhancement of skill reproduction five days after training results from “prolonged” consolidation of memory, during which it undergoes reorganization, including molecular and morphological changes to neurons in the animals’ brains.
We studied the role of DNA methylation in the mechanisms of amnesia in edible snails, which was induced by impairment of conditioned food aversion memory reconsolidation with NMDA glutamate receptor ...antagonist. The effects of DNA methyltransferase inhibitors were shown to depend on the stage of amnesia. At the early stage of amnesia (day 3 after induction), injections of methyltransferase inhibitors in combination with conditioned food stimulus (reminder) were followed by memory recovery. Application of inhibitors in the absence of the reminder was ineffective. Methyltransferase inhibitors were ineffective at the late stage of amnesia (day 10). Our results suggest that the presentation of reminding conditioned stimuli is followed by reactivation of amnesia. Methylation or demethylation of DNA in nerve cells serves as one of the key mechanisms for amnesia.
The effect of MK-801, an antagonist to NMDA-glutamate receptors, on reconsolidation of olfactory discrimination task in rats and taste discrimination in edible snails was examined. Twenty-four hours ...after conditioning, the animals received a single systemic injection of MK-801 followed by a reminding conditional stimulus. Disturbances in retrieval of the acquired task were observed 10 days after injection followed by a reminding procedure. Repeated conditioning of these animals did not restore the task. Injection of MK-801 without reminding stimulation had no effect on task retention. Thus, disturbances of NMDA-dependent reconsolidation of the associative memory in animals of different taxonomic groups irreversibly eliminated long-term memory.
