Methylphenidate during early consolidation affects long-term associative memory retrieval depending on baseline catecholamines

RATIONALE: Synaptic memory consolidation is thought to rely on catecholaminergic signaling. Eventually, it is followed by systems consolidation, which embeds memories in a neocortical network. Although this sequence was demonstrated in rodents, it is unclear how catecholamines affect memory consolidation in humans. OBJECTIVES: Here, we tested the effects of catecholaminergic modulation on synaptic and subsequent systems consolidation. We expected enhanced memory performance and increased neocortical engagement during delayed retrieval. Additionally, we tested if this effect was modulated by individual differences in a cognitive proxy measure of baseline catecholamine synthesis capacity. METHODS: Fifty-three healthy males underwent a between-subjects, double-blind, placebo-controlled procedure across 2 days. On day 1, subjects studied and retrieved object-location associations and received 20 mg of methylphenidate or placebo. Drug intake was timed so that methylphenidate was expected to affect early consolidation but not encoding or retrieval. Memory was tested again while subjects were scanned three days later. RESULTS: Methylphenidate did not facilitate memory performance, and there was no significant group difference in activation during delayed retrieval. However, memory representations differed between groups depending on baseline catecholamines. The placebo group showed increased activation in occipito-temporal regions but decreased connectivity with the hippocampus, associated with lower baseline catecholamine synthesis capacity. The methylphenidate group showed stronger activation in the postcentral gyrus, associated with higher baseline catecholamine synthesis capacity. CONCLUSIONS: Altogether, methylphenidate during early consolidation did not foster long-term memory performance, but it affected retrieval-related neural processes depending on individual levels of baseline catecholamines

Quantum chemical modelling of the oxidation of myoglobin

The electronic structure (charge distribution, bond indices) and the geometry (bond distances and angles) of the deoxyheme and the oxyheme with coordinated proximal histidine in their reduced and oxidized form were determined by the INDO method. The effect of the distal histidine (in the case of the oxyheme) and a water molecule (in the case of the metheme) on the geometry, charge distribution and stability of the systems was investigated. The method was adopted to model the oxidation of myoglobin in biological systems. The results revealed that both deoxy- and oxymyoglobin could spontaneously undergo one-electron oxidation. The mechanistic considerations based on the charge distribution and energetic effects led to the conclusion, that in oxymyoglobin’s case the electron transfer are followed by dissociation of a dioxygen molecule and addition of a water molecule, where both processes proceed in parallel