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To understand cognition, it is important to understand how a learned response becomes a long-lasting memory. This process of memory consolidation has been modeled extensively using one-trial avoidance learning, in which animals (or humans) establish a conditioned response by learning to avoid danger in just one trial. This relies on molecular events in the CA1 region of the hippocampus that resemble those involved in CA1 long-term potentiation (LTP), and it also requires equivalent events to occur with different timings in the basolateral amygdala and the entorhinal, parietal and cingulate cortex. Many of these steps are modulated by monoaminergic pathways related to the perception of and reaction to emotion, which at least partly explains why strong and resistant consolidation is typical of emotion-laden memories. Thus memory consolidation involves a complex network of brain systems and serial and parallel molecular events, even for a task as deceptively simple as one-trial avoidance. We propose that these molecular events might also be involved in many other memory types in animals and humans. [Copyright &y& Elsevier]

Abstract: Evidences indicate that extinction represents a NMDA receptor (NMDAr)-dependent learning rather than erasure of previously stored information. Several members of the Src family of tyrosine kinases are activated by stimulation of the NMDAr and are involved in both induction of hippocampal long-term potentiation and consolidation of hippocampal-dependent, NMDAr-sensitive, memories. Here we analyzed the role of the Src family within the CA1 region of the hippocampus in extinction and reacquisition of the memory for step-down, inhibitory avoidance learning task (IA). Rats trained in IA were submitted to 5 daily extinction sessions during which the avoidance response was elicited in the absence of the unconditioned stimulus. Immediately or 180 min after each extinction session animals received intra-CA1 infusions of either 0.1% DMSO, the Src-family inhibitor PP2 or its inactive analog, PP3. PP2 blocked extinction of the IA response which was otherwise evident in DMSO and PP3-treated animals. After being submitted to a new training session the animals reacquired the avoidance response; however, they failed to do so if they received intra-CA1 infusions of PP2 immediately following retraining. Our results indicate that, like the original learning, extinction and reacquisition of the IA response require activity of the Src family in the CA1 region of the hippocampus. [Copyright &y& Elsevier]

Object recognition memory (ORM) allows identification of previously encountered items and is therefore crucial for remembering episodic information. In rodents, reactivation during recall in the presence of a novel object destabilizes ORM and initiates a Zif268 and protein synthesis-dependent reconsolidation process in the hippocampus that links the memory of this object to the reactivated recognition trace. Hippocampal NMDA receptors (NMDARs) modulate Zif268 expression and protein synthesis and regulate memory stability but their possible involvement in the ORM destabilization/reconsolidation cycle has yet to be analyzed in detail. We found that, in adult male Wistar rats, intra dorsal-CA1 administration of the non-subunit selective NMDAR antagonist AP5, or of the GluN2A subunit-containing NMDAR antagonist TCN201, 5 min after an ORM reactivation session in the presence of a novel object carried out 24 h post-training impaired retention 24 h later. In contrast, pre-reactivation administration of the GluN2B subunit-containing NMDAR antagonist RO25–6981 had no effect on ORM recall or retention but impeded the amnesia caused by Zif268 silencing and protein synthesis inhibition in dorsal CA1. Our results indicate that GluN2B-containing hippocampal NMDARs are necessary for ORM destabilization whereas GluN2A-containing NMDARs are involved in ORM reconsolidation, and suggest that modulation of the relative activity of these receptor subtypes during recall regulates ORM persistence. [ABSTRACT FROM AUTHOR]

Abstract: Compounds isolated from different members of the Amaryllidaceae family are becoming relevant options for the treatment of neurological disorders and neurodegenerative diseases. In particular, species of the Hippeastrum genus are important source of alkaloids with a wide profile of putative therapeutical applications. Here, we report on the behavioral and pharmaco-toxicological characterization of montanine, an isoquinoline alkaloid isolated from Hippeastrum vittatum, an ornamental plant found throughout the world. In mice, montanine showed a LD50 of 64.7 mg/kg and 67.6 mg/kg for male and female, respectively. When given i.p., montanine dose-dependently decreased sodium pentobarbital-induced sleep, protected against pentylenetetrazole-provoked convulsions, increased the number of entries and the time spent in the open arms of an elevated plus maze and augmented the time spent struggling during a forced swimming test. When given immediately after inhibitory avoidance training, montanine did not affect avoidance memory retention in rats. Our results suggest that montanine, as other alkaloids isolated from Amaryllidaceae species, has psychopharmacological activities including anxiolytic, antidepressive and anticonvulsive effects. [Copyright &y& Elsevier]

Object recognition memories (ORM) can incorporate new information upon reactivation. This update initially involves destabilization of the original memory, which is followed by restabilization of the upgraded engram through a reconsolidation process that requires gene expression and protein synthesis in the hippocampus. We found that when given in dorsal CA1 either immediately after training or 15 min before ORM reactivation in the presence of a novel object, the dopamine D 1 /D 5 receptor antagonist SCH23390 did not affect ORM consolidation, expression or retention but impeded the amnesia caused by the post-retrieval administration of the mRNA synthesis inhibitor α-amanitin or the protein synthesis blocker anisomycin. This anti-amnesic effect was not observed when SCH23390 was given immediately after training and again 15 min before memory reactivation. Our results demonstrate that hippocampal D 1 /D 5 receptors are not needed for formation, retrieval or post-retrieval restabilization of the ORM trace but are essential for its destabilization when reactivation occurs together with the incorporation of new information into the original memory. Importantly, they also suggest that reenactment of the animal's post-learning neurochemical milieu at the moment of memory reactivation can be a boundary condition for reconsolidation. [ABSTRACT FROM AUTHOR]

Abstract: The ability to regulate cell cycle progression and apoptosis through the activation of nuclear receptors and gene transcription has been generally accepted as a potential chemopreventive and therapeutic property of retinoids. However, recent studies suggest that retinol and related compounds can exert rapid and non-genomic effects, which may increase the production of reactive oxygen species (ROS) and lead to cell cycle disruption and malignant transformation. In this work, we report that, in Sertoli cells, retinol (7 μM) induces the Src-dependent activation of ERK1/2 MAPK and the ERK1/2-mediated phosphorylation of the transcription factor CREB. We found that these retinol-induced effects were completely blocked by the antioxidant Trolox 100 μM (a hydrophilic analogue of alpha-tocopherol), the hydroxyl radical scavenger mannitol (1 mM) and the addition of native superoxide dismutase (200 U/ml), and also that retinol increased the production of ROS and several other parameters indicative of oxidative stress during the same incubation periods in which ERK1/2 and CREB were phosphorylated. The activation of the ERK1/2–CREB pathway appears to be involved in the onset of some of the malignant effects caused by retinol in Sertoli cells since inhibition of ERK1/2 activation blocked the retinol-induced cell transformation and proliferation. [Copyright &y& Elsevier]

Abstract: Hippocampal α- and βI/βII protein kinase C (PKC) are crucial for the formation of different types of memory in several species, including that for a one trial inhibitory avoidance (IA) task in rats. Many studies, however, have shown that other brain structures besides the hippocampus, notably the basolateral amygdala (BLA) and posterior parietal cortex (PC) are also necessary for memory consolidation. Here, we examine the role of α- and βI/βII PKC in the BLA and PC on the consolidation of the memory for IA in rats. The selective inhibitor of α- and βI/βII-PKC Gö 6976 and the nonselective PKC inhibitor Gö 7874 were administered into these structures at different times after training at concentrations known to inhibit PKC and to produce retrograde amnesia when given into the hippocampus. Gö 7874 blocked consolidation of IA memory when infused into BLA immediately and 30 min or into PC 180 to 360 min posttraining. Gö 6976 caused amnesia when given into the BLA also immediately or 30 min posttraining but in the PC hindered memory retention only when infused 270 and 360 min after the training session. Our data indicate that α- and βI/βII-PKC are critical for consolidation of IA memory shortly after training in BLA and that, first other isoforms and subsequently the α- and βI/βII PKC are required 3 or more hours after training in the PC. The findings on BLA are similar to those previously reported in the hippocampus, but those on PC suggest an entirely different molecular dynamics for memory formation in that area. [Copyright &y& Elsevier]