2-Deoxygalactose interferes with an intermediate processing stage of memory

doi:10.1016/S0163-1047(05)80002-0

Behavioral and Neural Biology

Volume 61, Issue 3, May 1994, Pages 206-213

https://doi.org/10.1016/S0163-1047(05)80002-0 Get rights and content

The effect of 2-deoxygalactose (2-D-gal), an inhibitor of glycoprotein synthesis, on memory formation was investigated with the day-old chick trained on a single-trial passive discrimination task. 2-D-gal (10 μmol/chick) was shown to inhibit memory formation at a time before the emergence of an antibiotic-sensitive long-term memory stage. The amnestic effect of 2-D-gal was successfully prevented by galactose, and more significantly by noradrenaline. In contrast, anisomycin-induced amnesia was resistant to challenge by either galactose or noradrenaline. The results are consistent with the view that some glycoprotein involvement in memory formation occurs prior to the formation of protein synthesis-dependent long-term memory, and this role of glycoproteins may be associated with the triggering of long-term memory formation by noradrenaline.

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Cited by (18)

Chloramphenicol-induced amnesia for passive avoidance training in the day-old chick
1999, Neurobiology of Learning and Memory
The antibiotic chloramphenicol, an inhibitor of mitochondrial protein synthesis, was used to investigate the time-related changes in protein synthesis following passive avoidance training in the day-old chick (white leghorn–black Australorp). Retention of memory for this simple learning task is known to be prevented by an inhibitor of cytosolic protein synthesis, anisomycin, in a biphasic manner, with the first phase of sensitivity occurring up to 90 min post-training and the second phase between 4 and 5 h post-training (Freeman, Rose, & Scholey, 1995). Birds received bilateral intracranial injections of chloramphenicol (10 μl/hemisphere of a 7.4 mM solution) at various times relative to training and were tested 24 h later. This report shows that at the second phase of anisomycin susceptibility there was a chloramphenicol-sensitive period (5 h post-training) which had an onset time less than 1 h after injection. The effect of chloramphenicol appears not to be due to the mitochondria being energetically compromised since intracranial injections of an uncoupler of mitochondrial oxidative phosphorylation, 2,4-dinitrophenol (0.1 mM), did not disrupt memory formation when injected 5 h after training, even though it did cause amnesia when injected at the earlier time point of 20 min post-training. These results are discussed in the context of what is already known about memory formation in the day-old chick.
2-Deoxy-D-galactose effects on passive avoidance memorization in the rat
1997, Neurobiology of Learning and Memory
2-Deoxy-d-galactose (do-gal) hinders glycoprotein fucosylation. This compound was intracerebroventricularly administered to male adult Wistar rats in order to assess whether it could exert amnesic effects on a passive avoidance response (PAR) to be learned in the light–dark box apparatus. Three experiments were performed. In the first, do-gal was administered immediately after the acquisition trials at three dosages (2, 4, and 8 μmol). It was found that only the 4-μmol dosage was followed by PAR disruption. In the second, do-gal was administered at the adequate dosage (4 μmol) either 30 min before the acquisition trial or 30 min before retrieval testing. It was found that only the preretrieval administration was followed by PAR impairment. In the third, do-gal (4 μmol) was administered in postacquisition, at increasing postacquisition delays (0.25, 1.5, 4, and 6 h). It was found that there was PAR disruption only after do-gal administration at the shortest (0.25 h) delay. The results confirm that in the rat, glycoprotein fucosylation is involved in some of the phases of memory trace processing, and they are discussed in relation to other findings in the rat and the chick.
D-Cycloserine causes transient enhancement of memory for a weak aversive stimulus in day-old chicks (Gallus domesticus)
1996, Neurobiology of Learning and Memory
TheN-methyl-D-aspartate (NMDA) receptor plays an important role in acquisition of memory after one-trial passive avoidance training in day-old chicks. Here, we examined the effect ofD-cycloserine, a partial agonist of the glycine site on the NMDA receptor, on memory retention after training on weak aversive stimuli (10% methyl anthranilate). Bilateral, or unilateral, intracranial injections of 5 μl of 600 μmol·l⁻¹D-cycloserine (DCS) were made into the intermediate and medial hyperstriatum ventrale 5 min posttraining and chicks were tested either 30 min or 1, 6, or 24 h later. Enhanced memory retention (number of chicks avoiding) occurred after bilateral, or left hemisphere, injections of DCS (compared to saline-injected controls), when chicks were tested at 1 and 6 h, but not at 30 min or 24 h posttraining. These data suggest that activation of the glycine site on the NMDA receptor in the immediate posttraining period can transiently extend the retention period of memory for a weak aversive stimulus.
Involvement of glutamate receptors, protein kinases, and protein synthesis in memory for visual discrimination in the young chick
1996, Neurobiology of Learning and Memory
Two-day-old chicks were trained to discriminate between edible chick crumbs and arrays of colored beads glued to the floor of their cage. Normal chicks learned this task within a few minutes and retained it for at least 24 h. The role of several biochemical systems known to be required for other forms of early learning in the chick was explored in this task. Antagonists and inhibitors of these systems were used in the doses known to produce amnesia in a related passive avoidance learning model. Drugs were injected intracerebrally just before training, and retention was tested at various times subsequently. The protein synthesis inhibitor anisomycin (240 nmol/chick) was without effect on retention at 30 min posttraining, but chicks were amnestic at 3 and 24 h. The protein kinases inhibitors melittin (1.2 nmol/chick) and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine hydrochloride (100 nmol/chick) were without effect on retention at 30 min posttraining but were amnestic by 3 h. While these effects are similar to those found for one-trial passive avoidance training, neither theN-methyl-D-aspartate receptor antagonists (+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten-5,10-imine maleate (up to 15 nmol/chick) orDL-2-amino-5-phosphonovalerate (1.3 nmol/chick), both of which are amnestic for passive avoidance, nor the non-NMDA-glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3,-dione (4 nmol/chick) were amnestic for the visual discrimination task. By contrast, the metabotropic glutamate receptor blocker (RS)-α-methyl-4-carboxyphenylglycine (300 nmol/chick) injected 5 min pretraining resulted in amnesia at 3 h posttraining. The implications of these findings for the putative “memory consolidation cascade” are discussed.
Cell adhesion molecules and the transition from short- to long-term memory
1996, Journal of Physiology Paris
Training chicks on a one-trial passive avoidance task results in a cascade of molecular and cellular processes in two forebrain regions, culminating within 60–90 min in post-translational glycosylation of synaptic membrane proteins and expression of immediate early genes c-fos and c-jun. We have now found a second window of vulnerability of memory to the protein synthesis inhibitor anisomycin, 4 h downstream of training. By 5.5 h post-training this window closes, to be replaced by a window of sensitivity to blockade of glycoprotein synthesis, presumably representing post-translational modification of the newly synthesised proteins. Amongst the pre- and post-synaptic membrane glycoproteins involved at both first and second time windows are the cell adhesion molecules, L1 (at both times) and NCAM (at the later). Molecular dissection of the external membrane domains of L1 distinguishes between a requirement for the IgG domain at the early time, the fibronectin-like domain at the later. The second time window only occurs if the animal is trained on a stimulus strong enough to be remembered for a long period. Weak memories do not persist beyond 6–8 h and the second wave of glycoprotein synthesis does not occur. Thus the second wave may represent the molecular processes required for the alterations in synaptic configuration, by way of the adhesion molecules amongst others, required for the morphological changes in neuronal connectivity hypothesised to encode memory.
Administration of glutamate following a reminder induces transient memory loss in day-old chicks
1995, Cognitive Brain Research
Monosodium glutamate (4.0 mM) administered immediately after a visual reminder presented to day-old chickens between 7.5 min and 24 h following a single trial passive avoidance learning task produced transient losses of memory on retention test, an effect not observed in the absence of a reminder or when the reminder was given 48 h post-learning. The duration of the transient deficit decreased with increasing interval between the training and the reminder trial. The time of onset of memory loss after the reminder trial appeared to increase with increasing interval between the training and the reminder trials. The results suggest that, for a period of at least up to 24 h after passive avoidance training, retrieval of memory may lead to processes which are sensitive to inhibition by glutamate, with the duration of sensitivity post-retrieval decreasing as the period of memory consolidation increases. The results extend previously reported findings with rodents and suggest the possibility that consolidation of a stable memorial representation of a learning experience may take place over several days and may entail the concurrent laying down of a stable retrieval mechanism.

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¹: The authors thank the Australian Research Council for agrant enabling this study. We are particularly grateful also to Professor Steven Rose of the Open University, United Kingdom, for making available prepublication data which, together with his valuable suggestions, enabled us to interpret our findings more meaningfully.

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2-Deoxygalactose interferes with an intermediate processing stage of memory

Pharmacology, Biochemistry and Behavior

Behavioral and Neural Biology

Physiology and Behavior

Behavioural Brain Research

Brain Research

Journal of Neuroimmunology

Behavioral and Neural Biology

Progress in Neurobiology

Neuroscience

Pharmacology, Biochemistry and Behavior

2-Deoxy-d-galactose impairs the fucosylation of glycoproteins of rat liver and Morris hepatoma

European Journal of Biochemistry