Protein synthesis- and fucosylation-dependent mechanisms in corticosterone facilitation of long-term memory in the chick

Long-term memory formation for a passive avoidance task in day-old chicks, which requires a late phase of glycoprotein fucosylation (5-8 hr posttraining), is dependent on a corticosterone action in the brain. In addition, corticosterone enhances late-phase fucosylation. In this study, the authors explored (a) to what extent the memory-facilitating action of corticosterone is dependent on protein fucosylation and (b) whether a protein synthesis mechanism might be involved in the steroid effects on memory and late-phase fucosylation. A combination of psychopharmacological and biochemical experiments, including the fucosylation inhibitor 2-deoxygalactose (2-DG), the protein synthesis inhibitor anisomycin (ANI), and radiolabeled fucose, indicated that the late phase of glycoprotein synthesis involved in the memory-facilitating effect of corticosterone occurs on newly synthesized proteins.

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

Effects of NMDA and AMPA receptor antagonists on corticosterone facilitation of long-term memory in the chick

Maria del Carmen Sandi Perez

Long-term memory formation for a weak passive avoidance task in day-old chicks is facilitated by corticosterone administration. Since (i) glutamatergic systems, through different receptor types, play a key role in learning and memory processes, and (ii) glucocorticoids increase glutamate concentrations in learning-related regions of the mammalian brain, we reasoned that glutamatergic activation might be a mechanism by which corticosterone facilitates the formation of an enduring memory. To assess this hypothesis, long-term retention was evaluated in chicks trained on a weak passive avoidance task and intracerebrally injected with NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists (MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione) with regard to training and corticosterone injection respectively. The results indicated that either of the antagonists prevented the facilitating effect of corticosterone when administered before the training trial, but failed to interfere with the steroid effect when injected before corticosterone administration in the post-training period, suggesting that their early effectiveness was not related to corticosterone-induced actions but to training-triggered mechanisms. In addition, administration of the AMPA antagonist, 5.5 h after training, was also effective in impairing the long-term memory-potentiating effect of corticosterone. These results support the view that corticosterone facilitates the formation of an enduring memory in this learning model, through the modulation of late events during the consolidation period, including the activation of the AMPA receptor type.

1997

Training-dependent biphasic effects of corticosterone in memory formation for a passive avoidance task in chicks

Maria del Carmen Sandi Perez

This study investigates the functional role of corticosterone in memory formation for a passive avoidance task in the day-old chick. Whereas training chicks with a strong aversant results in an enduring memory, memory for a weak aversant which is only retained for a few hours (< 9 h) is facilitated by intracerebral corticosterone administration. We now report that only chicks trained on the strong task, a learning situation that results in a high percentage of chicks (around 80%) forming a long-term memory, showed increased post-training plasma corticosterone levels, whereas chicks trained on the weak task showed corticosterone values comparable to untrained chicks. We also questioned whether the effects of corticosterone on retention might be concentration dependent. In the weak task, intracerebral administration of 1 microgram corticosterone facilitated retention, but a higher dose failed to induce this effect. However, in the strong task, corticosterone administration at doses of 1 and 5 micrograms produced an impairment in long-term retention for the avoidance response. These results support a crucial role of corticosterone release following training on the physiological mechanisms ensuring the transition from short- to long-term memory, and provide an animal learning model for the study of the mechanisms of action of a biphasic modulation of memory formation by acute corticosterone administration.

1997

Corticosterone facilitates long-term memory formation via enhanced glycoprotein synthesis

Maria del Carmen Sandi Perez

1995