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Mohammad Shehata, Kareem Abdou, Kiriko Choko, Mina Matsuo, Hirofumi Nishizono, Kaoru Inokuchi
There is substantial interest in memory reconsolidation as a target for the treatment of anxiety disorders such as post-traumatic stress disorder (PTSD). However, its applicability is restricted by reconsolidation-resistant boundary conditions that constrain the initial memory destabilization. In this study, we investigated whether the induction of synaptic protein degradation through autophagy modulation, a major protein degradation pathway, can enhance memory destabilization upon retrieval and whether it can be utilized to overcome these conditions...
March 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Shira Meir Drexler, Oliver T Wolf
During the postretrieval reconsolidation "window", memories can be disrupted, strengthened, or updated using various pharmacological and behavioral manipulations. Behavioral manipulations are more ecologically valid, thus allowing better understating of memory modification under natural conditions, but they can also be less potent compared to pharmacological interventions. In this review we present the current human and animal literature, aiming to understand the modulatory factors (i.e., task relevance, complexity, intensity) that promote reconsolidation disruption in purely behavioral means...
February 2018: Behavioral Neuroscience
Jocelyn Charlton, Timothy L Downing, Zachary D Smith, Hongcang Gu, Kendell Clement, Ramona Pop, Veronika Akopian, Sven Klages, David P Santos, Alexander M Tsankov, Bernd Timmermann, Michael J Ziller, Evangelos Kiskinis, Andreas Gnirke, Alexander Meissner
Cytosine methylation is widespread among organisms and essential for mammalian development. In line with early postulations of an epigenetic role in gene regulation, symmetric CpG methylation can be mitotically propagated over many generations with extraordinarily high fidelity. Here, we combine BrdU labeling and immunoprecipitation with genome-wide bisulfite sequencing to explore the inheritance of cytosine methylation onto newly replicated DNA in human cells. Globally, we observe a pronounced lag between the copying of genetic and epigenetic information in embryonic stem cells that is reconsolidated within hours to accomplish faithful mitotic transmission...
March 12, 2018: Nature Structural & Molecular Biology
Allison A Feduccia, Michael C Mithoefer
MDMA-assisted psychotherapy for treatment of PTSD has recently progressed to Phase 3 clinical trials and received Breakthrough Therapy designation by the FDA. MDMA used as an adjunct during psychotherapy sessions has demonstrated effectiveness and acceptable safety in reducing PTSD symptoms in Phase 2 trials, with durable remission of PTSD diagnosis in 68% of participants. The underlying psychological and neurological mechanisms for the robust effects in mitigating PTSD are being investigated in animal models and in studies of healthy volunteers...
March 7, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Daniel A Levy, Rotem Mika, Cecilia Radzyminski, Shir Ben-Zvi, Roni Tibon
In studies of behavioral reconsolidation interference, reactivation of a consolidated memory using some form of reminder is followed by the presentation of new information that can cause interference with that memory. Under these conditions, the interference not only impairs retrieval by indirect processes such as cue interference, but supposedly disrupts the original memory trace directly. Almost all studies of behavioral reconsolidation interference in episodic memory in humans have employed between-subjects paradigms, and deduced reminder effects from intrusion errors...
March 6, 2018: Neurobiology of Learning and Memory
V P Nikitin, S V Solntseva, S A Kozyrev, P V Nikitin, A V Shevelkin
Elucidation of amnesia mechanisms is one of the central problems in neuroscience with immense practical application. Previously, we found that conditioned food presentation combined with injection of a neurotransmitter receptor antagonist or protein synthesis inhibitor led to amnesia induction. In the present study, we investigated the time course and features of two amnesias: induced by impairment of memory reconsolidation using an NMDA glutamate receptor antagonist (MK-801) and a serotonin receptor antagonist (methiothepin, MET) on snails trained with food aversion conditioning...
February 27, 2018: Behavioural Brain Research
Linda Marschner, An Schreurs, Benoit Lechat, Jesper Mogensen, Anton Roebroek, Tariq Ahmed, Detlef Balschun
Mild traumatic brain injury (mTBI) can lead to diffuse neurophysical damage as well as cognitive and affective alterations. The nature and extent of behavioral changes after mTBI are still poorly understood and how strong an impact force has to be to cause long-term behavioral changes is not yet known. Here, we examined spatial learning acquisition, retention and reversal in a Morris water maze, and assessed search strategies during task performance after a single, mild, closed-skull traumatic impact referred to as "minimal" TBI...
February 27, 2018: Behavioural Brain Research
Gürsel Çalışkan, Oliver Stork
Behavioural metaplasticity is evident in experience-dependent changes of network activity patterns in neuronal circuits that connect the hippocampus, amygdala and medial prefrontal cortex. These limbic regions are key structures of a brain-wide neural network that translates emotionally salient events into persistent and vivid memories. Communication in this network by-and-large depends on behavioural state-dependent rhythmic network activity patterns that are typically generated and/or relayed via the hippocampus...
February 21, 2018: Neurobiology of Learning and Memory
Emiliano Merlo, Amy L Milton, Barry J Everitt
Fully consolidated fear memories can be maintained or inhibited by retrieval-dependent mechanisms depending on the degree of re-exposure to fear cues. Short exposures promote memory maintenance through reconsolidation and long exposures promote inhibition through extinction. Little is known about the neural mechanisms by which increasing cue exposure overrides reconsolidation and instead triggers extinction. Using auditory fear conditioning in male rats, we analysed the role of a molecular mechanism common to reconsolidation and extinction of fear, ERK1/2 activation within the basolateral amygdala (BLA), after intermediate CS exposure events...
February 23, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
J Jane Zhang, Josué Haubrich, Matteo Bernabo, Peter S B Finnie, Karim Nader
Reconsolidation, a process by which long-term memories are rendered malleable following retrieval, has been shown to occur across many different species and types of memory. However, there are conditions under which memories do not reconsolidate, and the reasons for this are poorly understood. One emerging theory is that these boundary conditions are mediated by a form of metaplasticity: cellular changes through which experience can affect future synaptic plasticity. We review evidence that N-methyl-D-aspartate receptors (NMDARs) might contribute to this phenomenon, and hypothesize that resistance to memory destabilization may be mediated by the ratio of GluN2A/GluN2B subunits that make up these receptors...
February 20, 2018: Neurobiology of Learning and Memory
Tamila Shymansky, Emily Hughes, Cailin M Rothwell, Ken Lukowiak
The therapeutic efficacy of the synthetic β-adrenergic receptor blocker, propranolol, for the treatment of post-traumatic stress disorder (PTSD) is currently being debated. Mixed results have been published regarding propranolol's ability to disrupt the consolidation and reconsolidation of memories. Here, we use the invertebrate model Lymnaea to study propranolol's ability to disrupt consolidation of memories formed under varying various types of stress which cause differing degrees of emotional memory. We show that when propranolol is administered immediately following operant conditioning, only the consolidation process of memories enhanced by individual stressors (i...
February 3, 2018: Neurobiology of Learning and Memory
Mickaël Puaud, Zofia Ossowska, Jordan Barnard, Amy L Milton
RATIONALE: Animal models of alcohol-seeking are useful for understanding alcohol addiction and for treatment development, but throughput in these models is limited by the extensive pretraining required to overcome the aversive taste of ethanol. Work by Augier et al. (Psychopharmacology 231: 4561-4568, 2014) indicates that Wistar rats will self-administer alcohol without water deprivation, exposure to sweetened ethanol solutions or intermittent access to ethanol. OBJECTIVES AND METHODS: We sought to replicate and extend the work of Augier et al...
February 6, 2018: Psychopharmacology
Alessandro Piva, Elisabetta Gerace, Marzia Di Chio, Lisa Osanni, Laura Padovani, Lucia Caffino, Fabio Fumagalli, Domenico E Pellegrini-Giampietro, Cristiano Chiamulera
Metaplasticity, defined as the plasticity of synaptic plasticity, could affect learning and memory at different neural levels. It was hypothesized that metaplasticity changes on glutamate receptors may affect memory destabilization, promoting or preventing reconsolidation. We investigated the metaplastic effect of NMDA channel blocker MK-801 on sucrose instrumental memory reconsolidation in a behavioural rat model associated to the assessment of molecular markers of metaplasticity, memory retrieval, destabilization and reconsolidation...
January 31, 2018: Neurobiology of Learning and Memory
Ravi K Das, Grace Gale, Vanessa Hennessy, Sunjeev K Kamboj
Maladaptive reward memories (MRMs) can become unstable following retrieval under certain conditions, allowing their modification by subsequent new learning. However, robust (well-rehearsed) and chronologically old MRMs, such as those underlying substance use disorders, do not destabilize easily when retrieved. A key determinate of memory destabilization during retrieval is prediction error (PE). We describe a retrieval procedure for alcohol MRMs in hazardous drinkers that specifically aims to maximize the generation of PE and therefore the likelihood of MRM destabilization...
January 5, 2018: Journal of Visualized Experiments: JoVE
Hélène Villain, Aïcha Benkahoul, Philippe Birmes, Barbara Ferry, Pascal Roullet
Post-traumatic stress disorder (PTSD) is a common consequence of exposure to a life-threatening event. Currently, pharmacological treatments are limited by high rates of relapse, and novel treatment approaches are needed. We have recently demonstrated that propranolol, a β-adrenergic antagonist, inhibited aversive memory reconsolidation in animals. Following this, in an open-label study 70% of patients with PTSD treated with propranolol during reactivation of traumatic memory exhibited full remission. However, the reason why 30% of these patients did not respond positively to propranolol treatment is still unclear...
2018: PloS One
Renée M Visser, Alex Lau-Zhu, Richard N Henson, Emily A Holmes
Memories that have strong emotions associated with them are particularly resilient to forgetting. This is not necessarily problematic, however some aspects of memory can be. In particular, the involuntary expression of those memories, e.g. intrusive memories after trauma, are core to certain psychological disorders. Since the beginning of this century, research using animal models shows that it is possible to change the underlying memory, for example by interfering with its consolidation or reconsolidation...
March 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Merel Kindt
Current pharmacological and psychological treatments for disorders of emotional memory only dampen the affective response while leaving the original fear memory intact. Under adverse circumstances, these original memories regain prominence, causing relapses in many patients. The (re)discovery in neuroscience that after reactivation consolidated fear memories may return to a transient labile state, requiring a process of restabilization in order to persist, offers a window of opportunity for modifying fear memories with amnestic agents...
March 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Barry J Everitt, Chiara Giuliano, David Belin
Since the introduction of intravenous drug self-administration methodology over 50 years ago, experimental investigation of addictive behaviour has delivered an enormous body of data on the neural, psychological and molecular mechanisms of drug reward and reinforcement and the neuroadaptations to chronic use. Whether or not these behavioural and molecular studies are viewed as modelling the underpinnings of addiction in humans, the discussion presented here highlights two areas-the impact of drug-associated conditioned stimuli-or drug cues-on drug seeking and relapse, and compulsive cocaine seeking...
March 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
I Ivan Ezquerra-Romano, W Lawn, E Krupitsky, C J A Morgan
Ketamine is a dissociative anaesthetic drug which acts on the central nervous system chiefly through antagonism of the n-methyl-d-aspartate (NMDA) receptor. Recently, ketamine has attracted attention as a rapid-acting anti-depressant but other studies have also reported its efficacy in reducing problematic alcohol and drug use. This review explores the preclinical and clinical research into ketamine's ability to treat addiction. Despite methodological limitations and the relative infancy of the field, results thus far are promising...
January 12, 2018: Neuropharmacology
Alain Brunet, Daniel Saumier, Aihua Liu, David L Streiner, Jacques Tremblay, Roger K Pitman
OBJECTIVE: The authors assessed the efficacy of trauma memory reactivation performed under the influence of propranolol, a noradrenergic beta-receptor blocker, as a putative reconsolidation blocker, in reducing symptoms of posttraumatic stress disorder (PTSD). METHOD: This was a 6-week, double-blind, placebo-controlled, randomized clinical trial in 60 adults diagnosed with long-standing PTSD. Propranolol or placebo was administered 90 minutes before a brief memory reactivation session, once a week for 6 consecutive weeks...
January 12, 2018: American Journal of Psychiatry
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