The memory enhancing effect of the APP-derived tripeptide Ac-rER is mediated through CRMP2.

The diasteromeric (D/L) form of the acetylated tripeptide rER (NH2-D-arg-L-glu-D-arg-COOH), derived from the external domain of amyloid precursor protein, protects against amyloid-β induced memory loss for a passive avoidance task in young chicks and enhances retention for a weak version of the task when injected peripherally up to 12 h prior to training. The tripeptide readily crosses the blood-brain barrier, binds to receptor sites in the brain and is without adverse effects on general behaviour. The mechanisms of its action are unknown, as are its target molecules/pathways.

Memory beyond the synapse.

Based on studies of the molecular and cellular cascades that occur during memory consolidation for a one-trial passive-avoidance learning task in the young chick, I review the evidence that memory is encoded in permanent changes in synaptic connectivity ina specific brain region, the Hebb hypothesis. I conclude that despite the fact that such a cascade occurs, culminating in the synthesis of cell-adhesion molecules that are involved in synaptic remodelling, synaptic events are not in themselves sufficient to account for the phenomena of memory. Both whole brain (neuromodulator) and whole body (hormonal) processes are engaged.

Protection against Abeta-induced memory loss by tripeptide D-Arg-L-Glu-L-Arg.

The molecular and cellular mechanisms underlying the memory deficits in Alzheimer's disease are increasingly thought to be associated with faulty processing of amyloid precursor protein. Following our earlier findings that it is possible to use the tripeptide RER (NH2-D-Arg-L-Glu-L-Arg-COOH, derived from the external domain of amyloid precursor protein) to rescue memory in animal models, we report here that the diasteromeric (D/L) form of the acetylated tripeptide RER protects against Abeta-induced memory loss for a passive avoidance task in young chicks and enhances retention for a weak version of the task when injected peripherally up to 12 h before training. The tripeptide readily crosses the blood-brain barrier, binds to membrane receptor sites in the brain and is without adverse effects on general behaviour.

Recalling an aversive experience by day-old chicks is not dependent on somatic protein synthesis.

Long-term memory is dependent on protein synthesis and inhibiting such synthesis following training results in amnesia for the task. Proteins synthesized during training must be transported to the synapse and disrupting microtubules with Colchicines, and hence, blocking transport, results in transient amnesia. Reactivating memory for a previously learned avoidance triggers a biochemical cascade analogous to that following the initial training and renders the memory labile once more to protein synthesis inhibitors.

Human agency in the neurocentric age. Philosophers and scientists resort to dualistic explanations to reconcile the age-old dichotomy between determinism and 'free will', but agency is an integral part of human biology.

Philosophers and scientists resort to dualistic explanations to reconcile the age-old dichotomy between determinism and 'free will', but agency is an integral part of human biology

Glycan analysis of the chicken synaptic plasma membrane glycoproteins--a major synaptic N-glycan carries the LewisX determinant.

The majority of synaptic plasma membrane components are glycosylated. It is now widely accepted that this post-translational modification is crucial during the establishment, maintenance and function of the nervous system. Despite its significance, structural information about the glycosylation of nervous system specific glycoproteins is very limited.

Amyloid precursor protein: from synaptic plasticity to Alzheimer's disease.

The amyloid precursor protein (APP) has been shown to be implicated in age-associated plastic changes at synapses that might contribute to memory loss in Alzheimer's disease. As APP has previously been reported to have multiple functions during normal development, and as human and avian APP share 95% homology in amino acid sequence, we have employed a one-trial passive avoidance task in day-old chicks to study its role in the process of memory formation. Administration of anti-APP antibodies, raised against human APP, APP-antisense, and Abeta during pre-training, prevented memory formation without effects on general behavior or initial acquisition.

Sex differences in pregnenolone sulphate in the chick brain after training.

Pregnenolone and pregnenolone sulphate are potent memory enhancers when administered to rodents prior to various learning and memory paradigms. Here, we show that training on a passive avoidance task results in the increased concentration of pregnenolone sulphate in the medial striatum, formerly known as lobus parolfactorius of female but not male chicks. In addition, we demonstrated potential for neuronal synthesis of pregnenolone in the day-old chick brain, including in the intermediate medial mesopallium, formerly known as intermediate medial hyperstriatum ventrale and the medial striatum.

The distributed neuronal systems supporting choice-making in real-life situations: differences between men and women when choosing groceries detected using magnetoencephalography.

In this work, magnetoencephalography was used to study the temporal dynamics of neural responses in 16 subjects (eight women, eight men) choosing among different day-to-day consumer items. At short latencies (< 150 ms), the evoked responses showed striate and extrastriate cortical activation common to the processing of general objects. At about 300 ms, women activated preferentially left posterior cortices, whereas men activated preferentially right temporal cortices.

Reminder effects: the molecular cascade following a reminder in young chicks does not recapitulate that following training on a passive avoidance task.

Memory traces, once established, are no longer sensitive to disruption by metabolic inhibitors. However, memories reactivated by reminder are once again vulnerable, in a time-dependent manner, to amnestic treatment. To determine whether the metabolic events following a reminder recapitulate those following initial training we examined the temporal dynamics of amnesia induced by the protein synthesis inhibitor anisomycin and the glycosylation inhibitor 2-deoxygalactose.

Reminder effects - reconsolidation or retrieval deficit? Pharmacological dissection with protein synthesis inhibitors following reminder for a passive-avoidance task in young chicks.

It is generally accepted that memory formation involves an irreversible passage via labile phases to the stable form of 'long-term memory' impervious to amnestic agents such as protein synthesis inhibitors. However, recent experiments demonstrate that reactivation of memory by way of a reminder renders it labile to such inhibitors, suggesting that such retrieval is followed by a so-called reconsolidation process similar or identical in its cellular and molecular correlates to that occurring during the initial consolidation. We compared the effects of the protein synthesis inhibitor anisomycin and the glycoprotein synthesis inhibitor 2-deoxygalactose on the temporal dynamics and pharmacological sensitivity of initial consolidation and memory expression following a reminder in a one-trial passive-avoidance task in day-old chicks.

Amino acid release from the intermediate medial hyperstriatum ventrale (IMHV) of day-old chicks following a one-trial passive avoidance task.

Indirect evidence has implicated glutamate and gamma-amino butyric acid in memory formation for one-trial passive avoidance learning. We have further examined this by following the time course of glutamate and gamma-amino butyric acid release from slices prepared from the intermediate medial hyperstriatum ventrale of day-old chicks (Ross 1 Chunky) trained to avoid a bead covered in the aversant methylanthranilate. At various times after training, slices of left and right intermediate medial hyperstriatum ventrale were incubated in medium containing 50 mM potassium chloride and amino acid release was determined.

Memory Formation in Day-old Chicks Requires NMDA but not Non-NMDA Glutamate Receptors.

The non-competitive N-methyl-d-aspartate (NMDA) antagonist MK-801, injected intraperitoneally at 0.1 mg/kg, at times between 1 h before and 5 min after training chicks on a one-trial passive avoidance task, resulted in amnesia for the task on test 3 or 24 h subsequently. No amnesia was apparent at 24 h if chicks were injected between 1 and 6 h after training.

Learning-induced Increase of Immediate Early Gene Messenger RNA in the Chick Forebrain.

The immediate early genes c-fos and c-jun are activated rapidly in nerve cells in response to in vivo and in vitro stimulation. Because of their involvement in transcriptional regulation, the products of these genes have been proposed as nuclear signals for consolidation of long-term memory. However, no specific changes of immediate early gene expression in relation to learning have yet been reported.

Glycoprotein Synthesis Is Necessary for Memory of Sickness-Induced Learning in Chicks.

Can current biochemical models of memory account for sickness-induced learning? We show that chicks can form an association between pecking a coloured but tasteless lure and becoming ill (LiCl, i.p.) 30 min later.