Synaptic consolidation: from synapses to behavioral modeling

Synaptic plasticity, a key process for memory formation, manifests itself across different time scales ranging from a few seconds for plasticity induction up to hours or even years for consolidation and memory retention. We developed a three-layered model of synaptic consolidation that accounts for data across a large range of experimental conditions. Consolidation occurs in the model through the interaction of the synaptic efficacy with a scaffolding variable by a read-write process mediated by a tagging-related variable. Plasticity-inducing stimuli modify the efficacy, but the state of tag and scaffold can only change if a write protection mechanism is overcome. Our model makes a link from depotentiation protocols in vitro to behavioral results regarding the influence of novelty on inhibitory avoidance memory in rats.

Corticosterone facilitates long-term memory formation via enhanced glycoprotein synthesis

Maria del Carmen Sandi Perez

Long-term memory formation for a passive avoidance task in one-day-old chicks requires a late phase of synaptic glycoprotein synthesis (including the neural cell adhesion molecule), commencing 5.5 h post-training. This phase occurred in chicks trained with a strong, but not a weak aversant, which only retained this memory for a few hours (< 10). In addition, previous work has shown that a corticosteroid action through central corticosteroid receptors is also required for long-term passive avoidance memory. Here, we tested the hypothesis that the corticosteroid action on memory formation might be exerted via modulation of the late phase of neural glycoprotein synthesis. One-day-old chicks were used as experimental subjects. Incorporation of the radiolabelled glycoprotein precursor [3H]fucose into synaptic membranes of the chick forebrain was used as an index of glycoprotein fucosylation. Bilateral intracerebral injections of a corticosterone dose (0.5 micrograms/hemisphere) that facilitates long-term retention of weak learning were able to induce the late phase of glycoprotein synthesis in undisturbed chicks. A further experiment examined the effect of antibodies against the neural cell adhesion molecule on the facilitatory action of corticosterone on long-term memory for the weak passive avoidance training. Chicks trained on a weak aversant were injected with corticosterone (0.5 micrograms/hemisphere) 30 min post-training and testing occurred 24 h post-training. Administration of the neural cell adhesion molecule antibodies during the late phase (5.5 h post-training) blocked the facilitatory action of corticosterone on long-term memory. These findings further support the view that corticosteroids have a role in memory consolidation. In addition to previously proposed effects on gene transcription, these data suggest a post-translational glycosylation mechanism for the modulatory effect of corticosteroids on long-term memory formation.

1995

Post-training administration of a synthetic peptide ligand of the neural cell adhesion molecule, C3d, attenuates long-term expression of contextual fear conditioning

Maria del Carmen Sandi Perez

The neural cell adhesion molecule (NCAM) plays a key role in synaptic plasticity and memory formation. We have recently developed a synthetic peptide, termed C3d, which, through the binding to the first, N-terminal immunoglobulin-like (Ig) module in the extracellular portion of NCAM, has been shown to promote neurite outgrowth and synapse formation in vitro, and to interfere with passive avoidance memory in rats in vivo. In this study, we investigated whether the i.c.v. administration of C3d, either 5.5 h after or 2 days before training, could be effective to modulate the strength at which emotional memory for aversive situations is established into a long-term memory. The effects of the peptide were evaluated in adult male Wistar rats trained in the contextual fear conditioning task. The results indicated that C3d significantly reduced the subsequent long-term retention of the conditioned fear response when administered 5.5 h post-training, as indicated by retention tests performed 2-3 and 7 days post-training. However, this treatment failed to influence conditioning for this task when injected 2 days pre-training. Additional experiments showed that C3d did not influence the emotional or locomotor behaviour of the animals, when tested in the open field task. Furthermore, hippocampal levels of microtubule-associated protein 2 (MAP2), Synaptophysin and NCAM were found unchanged when evaluated by enzyme-linked immunosorbent assay in crude synaptosomal preparations 2 days after peptide i.c.v. injection. Therefore, post-training injection of this synthetic peptide was efficient to attenuate the strength at which memory for contextual fear conditioning was enduringly stored, whilst it did not affect the acquisition of new memories. In addition to further support the view that NCAM is critically involved in memory consolidation, the current findings suggest that the NCAM IgI module is a potential target for the development of therapeutic drugs capable to reduce the cognitive impact induced by exposure to intensive stress experiences.

2003

Learning under stress: a role for the neural cell adhesion molecule NCAM

Reto Bisaz, Lisa Conboy, Maria del Carmen Sandi Perez

Stress is known to be a potent modulator of brain function and cognition. While prolonged and/or excessive stress generally exerts negative effects on learning and memory processes, acute stress can have differential effects on memory function depending on a number of factors (such as stress duration, stress intensity, timing and the source of the stress, as well as the learning type under study). Here, we have focused on the effects of 'acute' stress, and examined the literature attending to whether the "source of stress" is 'intrinsic' (i.e., when stress is originated by the cognitive task) or 'extrinsic' (i.e., when stress is induced by elements not related to the cognitive task). We have questioned here whether the neural cell adhesion molecule of the immunoglobulin superfamily (NCAM) contributes to the neurobiological mechanisms that translate the effects of these two different stress sources into the different behavioral and cognitive outcomes. NCAM is a cell adhesion macromolecule known to play a critical role in development and plasticity of the nervous system. NCAM and its post-translational modified form PSA- NCAM are critically involved in mechanisms of learning and memory and their expression levels are known to be highly susceptible to modulation by stress. Whereas available data are insufficient to conclude as to whether NCAM mediates extrinsic stress effects on learning and memory processes, we present systematic evidence supporting a key mediating role for both NCAM and PSA-NCAM in the facilitation of memory consolidation induced by intrinsic stress. Furthermore, NCAM is suggested to participate in some of the bidirectional effects of stress on memory processes, with its enhanced synaptic expression involved in facilitating stress actions while its reduced expression being related to impairing effects of stress on memory function

Elsevier2009

Corticosterone facilitates long-term memory formation via enhanced glycoprotein synthesis

Maria del Carmen Sandi Perez

1995

Post-training administration of a synthetic peptide ligand of the neural cell adhesion molecule, C3d, attenuates long-term expression of contextual fear conditioning

Maria del Carmen Sandi Perez

2003

Learning under stress: a role for the neural cell adhesion molecule NCAM

Reto Bisaz, Lisa Conboy, Maria del Carmen Sandi Perez

Elsevier2009