Neurobiology of learning and memory
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Neurobiol Learn Mem · Mar 2013
Activation of the basolateral amygdala induces long-term enhancement of specific memory representations in the cerebral cortex.
The basolateral amygdala (BLA) modulates memory, particularly for arousing or emotional events, during post-training periods of consolidation. It strengthens memories whose substrates in part or whole are stored remotely, in structures such as the hippocampus, striatum and cerebral cortex. However, the mechanisms by which the BLA influences distant memory traces are unknown, largely because of the need for identifiable target mnemonic representations. ⋯ BLA-induced tuning shifts were associative, highly specific and long-lasting. We propose that the BLA strengthens memory for important experiences by increasing the number of neurons that come to best represent that event. Traumatic, intrusive memories might reflect abnormally extensive representational networks due to hyper-activity of the BLA consequent to the release of excessive amounts of stress hormones.
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Neurobiol Learn Mem · Oct 2012
Dissociation between memory reactivation and its behavioral expression: scopolamine interferes with memory expression without disrupting long-term storage.
The reconsolidation hypothesis has challenged the traditional view of fixed memories after consolidation. Reconsolidation studies have disclosed that the mechanisms mediating memory retrieval and the mechanisms that underlie the behavioral expression of memory can be dissociated, offering a new prospect for understanding the nature of experimental amnesia. The muscarinic antagonist scopolamine has been used for decades to induce experimental amnesias The goal of the present study is to determine whether the amnesic effects of scopolamine are due to storage (or retrieval) deficits or, alternatively, to a decrease in the long-term memory expression of a consolidated long-term memory. ⋯ This recovery of memory expression was reconsolidation specific since a reminder that does not triggers reconsolidation process did not allow the recovery. A higher dose (5 μg/g) of scopolamine induced an amnesic effect that could not be reverted through reconsolidation, and thus it can be explained as an interference with memory storage and/or retrieval mechanisms. These results, showing that an effective amnesic dose of scopolamine (100 ng/g) negatively modulates long-term memory expression but not memory storage in the crab Chasmagnathus, are consistent with the concept that dissociable processes underlie the mechanisms mediating memory reactivation and the behavioral expression of memory.
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Neurobiol Learn Mem · Oct 2012
Maternal deprivation induces deficits in temporal memory and cognitive flexibility and exaggerates synaptic plasticity in the rat medial prefrontal cortex.
Early life adverse events can lead to structural and functional impairments in the prefrontal cortex (PFC). Here, we investigated whether maternal deprivation (MD) alters PFC-dependent executive functions, neurons and astrocytes number and synaptic plasticity in adult male Long-Evans rats. The deprivation protocol consisted of a daily separation of newborn Long-Evans pups from their mothers and littermates 3h/day postnatal day 1-14. ⋯ In parallel, MD induced in the prelimbic area of the medial PFC an upregulation of long-term potentiation (LTP), without any change in the number of neurons and astrocytes. We provide evidence that MD leads in adults to an alteration of the cognitive abilities dependent on the PFC, and to an exaggerated synaptic plasticity in this region. We suggest that this latter phenomenon may contribute to the impairments in the cognitive tasks.
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Neurobiol Learn Mem · Jul 2012
Increased levels of conditioned fear and avoidance behavior coincide with changes in phosphorylation of the protein kinase B (AKT) within the amygdala in a mouse model of extremes in trait anxiety.
Patients diagnosed for anxiety disorders often display faster acquisition and slower extinction of learned fear. To gain further insights into the mechanisms underlying these phenomenona, we studied conditioned fear in mice originating form a bi-directional selective breeding approach, which is based on elevated plus-maze behavior and results in CD1-derived high (HAB), normal (NAB), and low (LAB) anxiety-related behavior mice. HAB mice displayed pronounced cued-conditioned fear compared to NAB/CD1 and LAB mice that coincided with increased phosphorylation of the protein kinase B (AKT) in the basolateral amygdala 45 min after conditioning. ⋯ Taken together, our results suggest that the genetic predisposition to high anxiety-related behavior may increase the risk of forming traumatic memories, phobic-like fear and avoidance behavior following aversive encounters, with a clear bias towards passive coping styles. In contrast, genetic predisposition to low anxiety-related and high risk-taking behavior seems to be associated with an increase in active coping styles. Our data imply changes in AKT phosphorylation as a therapeutic target for the prevention of exaggerated fear memories.
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Neurobiol Learn Mem · May 2012
Histone acetylation rescues contextual fear conditioning in nNOS KO mice and accelerates extinction of cued fear conditioning in wild type mice.
Epigenetic regulation of chromatin structure is an essential molecular mechanism that contributes to the formation of synaptic plasticity and long-term memory (LTM). An important regulatory process of chromatin structure is acetylation and deacetylation of histone proteins. Inhibition of histone deacetylase (HDAC) increases acetylation of histone proteins and facilitate learning and memory. ⋯ The facilitatory effect of NaB on extinction of cued fear memory of WT mice was confirmed in a study whereupon NaB was administered during extinction. Results suggest that (a) the rescue of contextual fear conditioning in nNOS KO mice is associated with NaB-induced increase in H3 histone acetylation and (b) the accelerated extinction of cued fear memory in WT mice is associated with NaB-induced increase in H4 histone acetylation. Hence, a single administration of HDAC inhibitor may rescue NO-dependent cognitive deficits and afford a long-term accelerating effect on extinction of fear memory of WT mice.