In contrast to models and theories that relate adult neurogenesis with the processes of learning and memory, almost no solid hypotheses have been formulated that involve a possible neurocomputational influence of adult neurogenesis on forgetting. Based on data from a previous study that implemented a simple but complete model of the main hippocampal circuitry (Weisz & Argibay, 2009), we now test this model under different situations to better study the case of remote memories. The results of this work show that following neurogenesis, the new, ongoing memories in the hippocampus are better retained than when no neurogenesis occurs at all, while the older memories are affected (to a lesser extent) by a special type of interference that is different from interference that occurs with an increasing number of memories per se. This work adds a new point of analysis in support of the interference view that might lead to the forgetting of memories in the hippocampus as they are transferred to neocortex for long-term storage, consistent with the Complementary Learning Systems models of system-level consolidation. Attention should be directed to the specific causes of interference; the results of this work signal a type of distortion of remote memories that is produced by the birth and the growth of new processing units, which results in a subtly impoverished retrieval as new neurons become active. The proposals of this model fit well with some empirical findings that are related to the issue. In the future, as new evidence emerges, we believe that this biological process, which is largely related to learning and memory, will also help to shape our ideas about normal forgetting and its possible contributions to system consolidation.
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http://dx.doi.org/10.1016/j.cognition.2012.07.002 | DOI Listing |
Alzheimers Dement
December 2024
School of Pharmacy, Chapman University, Irvine, CA, USA.
Background: Although novel treatments for Alzheimer's disease (AD) have begun to show modest therapeutic effects, agents that target hallmark AD pathology and offer neuroprotection are desired. Erythropoietin (EPO) is a glycoprotein hormone with neuroprotective effects but is faced with challenges including limited brain uptake and increased hematopoietic side effects with long-term dosing. Therefore, EPO has been modified and bound to a chimeric transferrin receptor monoclonal antibody (cTfRMAb); the latter shuttles EPO past the blood-brain barrier (BBB) into brain parenchyma and reduces its plasma exposure and potential for side effects.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Bioengineering, University of California, Los Angeles, CA, USA, Los Angeles, CA, USA.
Background: The initiation of amyloid plaque deposition signifies a crucial stage in Alzheimer's disease (AD) progression, which often coincides with the disruption of neural circuits and cognitive decline. While the role of excitatory-inhibitory balance is increasingly recognized in AD pathophysiology, targeted therapies to modulate this balance remain underexplored. This study investigates the effect of perampanel, a selective non-competitive AMPA receptor antagonist, in modulating neurophysiological changes in hAPP-J20 transgenic Alzheimer's mice.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Yonsei University, Incheon, Incheon, Korea, Republic of (South).
Background: Cyclin Y (CCNY) is a member of cyclin protein family inhibiting long-term synaptic plasticity, which is related to the learning and memory function in neuronal system. Recently, CCNY has been reported to associate with the cognitive deficits in Alzheimer's disease (AD).
Method: In this study, we discovered PFTAIRE peptide to diminish CCNY protein level and to ameliorate cognitive dysfunction in AD.
Background: Memory is influenced by epigenetic mechanisms that regulate gene expression. Histone acetyltransferases (HATs), and histone deacetylases (HDACs), are two competitive enzymes regulating histone acetylation. Histone acetylation is reduced in Alzheimer's disease (AD) brains, and evidence has shown a synergistic regulation of HDACs and HATs activities.
View Article and Find Full Text PDFBackground: There are no cures for Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by elevation of beta-amyloid and tau proteins besides neuronal death and causing cognitive impairment. Phosphodiesterase 5 (PDE5) is a cyclic guanosine monophosphate-degrading enzyme involved in numerous biological pathways including those relevant to memory formation. PDE5 inhibition offers the potential to attenuate AD progression by acting at the downstream level of beta-amyloid and tau elevation.
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