Neuroscience
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The endocannabinoid system is involved in the fine-tuning of local synaptic plasticity in the hippocampus during the initial steps of memory formation/transformation. In spite of extensive studies, endocannabinoid modulation of these processes is still poorly understood. Here we studied the effects of intra-CA1 infused AM404, an anandamide (AEA) transport/metabolism inhibitor, upon an aversive memory consolidation with or without prior systemic administration of metyrapone, as well the concomitant intra-CA1 administration of AM404 plus AM251 (CB1 receptor inverse-agonist), capsazepine (TRPV1 receptor antagonist) or tropicamide (M4 receptor antagonist). ⋯ This confirms that CB1 actually mediate the amnestic effect caused by the augmented AEA pool, but TRPV1 does not. The tropicamide result suggests an interesting comodulatory interaction between the endocannabinoid and the cholinergic systems. We propose a steady-state model centered in the idea of an optimal, stable extracellular concentration of anandamide as a necessary condition to ensure the consolidation of a stable memory trace in the CA1 area.
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Oxytocin (OT) and vasopressin (AVP) are two closely related neuropeptides implicated in learning and memory processes, anxiety, nociception, addiction, feeding behavior and social information processing. Regarding learning and memory, OT has induced long-lasting impairment in different behaviors, while the opposite was observed with AVP. We have previously evaluated the effect of peripheral administration of OT or its antagonist (AOT) on the inhibitory avoidance response of mice and on the modulation of cholinergic mechanisms. ⋯ Administration of anticholinesterases inhibitors with access to the central nervous system (CNS), the activation of muscarinic acetylcholine (Ach) receptors and the increase of evoked ACh release using linopirdine (Lino) (3-10 µg/kg, IP), reversed the impairment of retention performance induced by OT. Besides, either muscarinic or nicotinic antagonists with unrestricted access to the CNS reduced the magnitude of the performance-facilitating effect of AOT's central infusion. We suggest that OT might induce a cholinergic hypofunction state, resulting in an impairment of IA memory formation, a process for which the cholinergic system is crucially necessary.
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Spaced training, which involves long inter-trial intervals, has positive effects on memories. One of the main attributes of long-term memories (LTM) is persistence. Here, to identify the process that promotes LTM persistence by spaced learning, we used the spatial object recognition (SOR) task in rats. ⋯ Our results suggest that the mechanism of memory expression, but not those of memory reinforcement or reconsolidation, is necessary to promote memory persistence after retraining. The molecular mechanisms involve ERKs1/2 activity to set the SOR learning tag, and the availability of GluA2-containing AMPA receptor. In conclusion, both the synthesis of PRPs and the setting of learning tags are key processes triggered by retraining that allow SOR memory persistence.
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The contribution of amyloid-β (Aβ) soluble forms to Alzheimer's Disease (AD) is undergoing revision and the characterization of monomeric, oligomeric and protofibrillar Aβ forms used in vivo to model AD is a critical step to ensure data interpretation. Atomic force microscopy (AFM) was used to characterize the nanoscale morphology of different Aβ42 forms also used for cerebroventricular injection (cvi) in young (6mo) and aged (36mo) adult zebrafish behavioral and cognitive tests. On the AFM, monomeric solution deposited onto mica resulted mostly in thin filamentous structures and shorter monomeric agglomerates with heights around or below 1.5 nm, as expected for single Aβ42. ⋯ On the Open Tank used to test exploratory parameters, no differences were observed between injected animals and their age-matched controls, except for a reduced distance travelled by aged individuals that received the Aβ42 oligomeric form. Long-term memory (LTM) for the inhibitory avoidance task was not influenced by monomers cvi, whilst oligomeric and fibrillar Aβ42 hindered LTM formation in young and aged groups. Our findings support current views of deleterious effects of Aβ42 soluble forms on cognition and ensures that preparations were structurally unique and within expected morphologies and dimensions.
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Systemic administration of drugs that activate the noradrenergic or glucocorticoid system potentiates aversive memory consolidation and reconsolidation. The opposite happens with the stimulation of endocannabinoid signaling under certain conditions. An unbalance of these interacting neurotransmitters can lead to the formation and maintenance of traumatic memories, whose strength and specificity attributes are often maladaptive. ⋯ Neither the high nor the low dose of adrenaline, corticosterone, or AM251 altered freezing times at test in a novel, neutral context two and ten days later. In contrast, animals receiving the association of their low dose exhibited significantly higher freezing times than controls. Together, the results indicate that newly acquired and destabilized threat memory traces become more intense and generalized after a combined interference acting synergistically and mimicking that reported in patients presenting stress-related psychiatric conditions.