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Immediate early gene and memory retrieval

Anthony Holtmaat, Pico Caroni
Learning and memory are associated with the formation and modification of neuronal assemblies: populations of neurons that encode what has been learned and mediate memory retrieval upon recall. Functional studies of neuronal assemblies have progressed dramatically thanks to recent technological advances. Here we discuss how a focus on assembly formation and consolidation has provided a powerful conceptual framework to relate mechanistic studies of synaptic and circuit plasticity to behaviorally relevant aspects of learning and memory...
October 17, 2016: Nature Neuroscience
Joshua K Carr, Neil M Fournier, Hugo Lehmann
We examined whether increasing retrieval difficulty in a spatial memory task would promote the recruitment of the anterior cingulate cortex (ACC) similar to what is typically observed during remote memory retrieval. Rats were trained on the hidden platform version of the Morris Water Task and tested three or 30 d later. Retrieval difficulty was manipulated by removing several prominent extra-pool cues from the testing room. Immediate early gene expression (c-Fos) in the ACC was greater following the cue removal and comparable to remote memory retrieval (30-d retention interval) levels, supporting the view of increased ACC contribution during high cognitive-demand memory processes...
September 2016: Learning & Memory
Munir G Kutlu, Jessica M Tumolo, Erica Holliday, Brendan Garrett, Thomas J Gould
Exposure therapy, which focuses on extinguishing fear-triggering cues and contexts, is widely used to treat post-traumatic stress disorder (PTSD). Yet, PTSD patients who received successful exposure therapy are vulnerable to relapse of fear response after a period of time, a phenomenon known as spontaneous recovery (SR). Increasing evidence suggests ventral hippocampus, basolateral amygdala, and infralimbic cortex may be involved in SR. PTSD patients also show high rates of comorbidity with nicotine dependence...
August 2016: Learning & Memory
Anna Grosso, Marco Cambiaghi, Luisella Milano, Annamaria Renna, Tiziana Sacco, Benedetto Sacchetti
The auditory cortex is involved in encoding sounds which have acquired an emotional-motivational charge. However, the neural circuitry engaged by emotional memory processes in the auditory cortex is poorly understood. In this study, we investigated the layers and regions that are recruited in the higher order auditory cortex Te2 by a tone previously paired to either fear or appetitive stimuli in rats. By tracking the protein coded by the immediate early gene zif268, we found that fear memory retrieval engages layers II-III in most regions of Te2...
June 1, 2016: Cerebral Cortex
Shannon L Gourley, Kelsey S Zimmermann, Amanda G Allen, Jane R Taylor
UNLABELLED: An essential component of goal-directed decision-making is the ability to maintain flexible responding based on the value of a given reward, or "reinforcer." The medial orbitofrontal cortex (mOFC), a subregion of the ventromedial prefrontal cortex, is uniquely positioned to regulate this process. We trained mice to nose poke for food reinforcers and then stimulated this region using CaMKII-driven Gs-coupled designer receptors exclusively activated by designer drugs (DREADDs)...
April 20, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Vanessa Lux, Erika Atucha, Takashi Kitsukawa, Magdalena M Sauvage
Whether retrieval still depends on the hippocampus as memories age or relies then on cortical areas remains a major controversy. Despite evidence for a functional segregation between CA1, CA3 and parahippocampal areas, their specific role within this frame is unclear. Especially, the contribution of CA3 is questionable as very remote memories might be too degraded to be used for pattern completion. To identify the specific role of these areas, we imaged brain activity in mice during retrieval of recent, early remote and very remote fear memories by detecting the immediate-early gene Arc...
February 12, 2016: ELife
Daniel N Barry, Andrew N Coogan, Sean Commins
Systems consolidation is a process involving the stabilisation of memory traces in the neocortex over time. The medial prefrontal cortex becomes increasingly important during the retrieval of older memories, however the timescale of its involvement is unclear, and the contribution of other neocortical brain regions to remote memory have received little attention. The Immediate Early Genes (IEGs) Zif268, c-Fos and Arc have been utilised as markers of neural activity during spatial memory retrieval, however the lack of a direct comparison between them hinders the interpretation of results...
February 2016: Neurobiology of Learning and Memory
Jean-Pascal Morin, Kioko Guzmán-Ramos, Federico Bermudez-Rattoni
The mainstream view on the neurobiological mechanisms underlying memory formation states that memory traces reside on the network of cells activated during initial acquisition that becomes active again upon retrieval (reactivation). These activation and reactivation processes have been called "conjunctive trace." This process implies that singular molecular events must occur during acquisition, strengthening the connection between the implicated cells whose synchronous activity must underlie subsequent reactivations...
2015: Neural Plasticity
Natalia Arias, Marta Méndez, Guillermo Vallejo, Jorge L Arias
Mastering the Morris water maze (MWM) requires the animal to consolidate, retain and retrieve spatial localizations of relevant visual cues. However, it is necessary to investigate whether a reorganization of the neural networks takes place when part of the spatial information is removed. We conducted four experiments using the MWM. A classical reference memory procedure was performed over five training days, RM5 (n=7), and eight days, RM8 (n=7), with the whole room and all the spatial cues presented. Another group of animals were trained in the same protocol, but they received an additional day of training with only partial cues, PC (n=8)...
November 2, 2015: Brain Research
Jean-Bastien Bott, Marc-Antoine Muller, Jesse Jackson, Julien Aubert, Jean-Christophe Cassel, Chantal Mathis, Romain Goutagny
Spatial reference memory in rodents represents a unique opportunity to study brain mechanisms responsible for encoding, storage and retrieval of a memory. Even though its reliance on hippocampal networks has long been established, the precise computations performed by different hippocampal subfields during spatial learning are still not clear. To study the evolution of electrophysiological activity in the CA1-dentate gyrus axis of the dorsal hippocampus over an iterative spatial learning paradigm, we recorded local field potentials in behaving mice using a newly designed appetitive version of the Barnes maze...
September 2016: Cerebral Cortex
Sophie Tronel, Vanessa Charrier, Cyrille Sage, Marlene Maitre, Thierry Leste-Lasserre, Djoher N Abrous
Adult neurogenesis occurs in the dentate gyrus (DG) of the hippocampus, which is a key structure in learning and memory. Adult-generated granule cells have been shown to play a role in spatial memory processes such as acquisition or retrieval, in particular during an immature stage when they exhibit a period of increased plasticity. Here, we demonstrate that immature and mature neurons born in the DG of adult rats are similarly activated in spatial memory processes. By imaging the activation of these two different neuron generations in the same rat and by using the immediate early gene Zif268, we show that these neurons are involved in both spatial memory acquisition and retrieval...
November 2015: Hippocampus
Gisela Zalcman, Noel Federman, Verónica de la Fuente, Arturo Romano
Long-term memory formation requires gene expression after acquisition of new information. The first step in the regulation of gene expression is the participation of transcription factors (TFs) such as nuclear factor kappa B (NF-кB), which are present before the neuronal activity induced by training. It was proposed that the activation of these types of TFs allows a second step in gene regulation by induction of immediate-early genes (IEGs) whose protein products are, in turn, TFs. Between these IEGs, zif268 has been found to play a critical role in long-term memory formation and reprocessing after retrieval...
March 2015: Neurobiology of Learning and Memory
Aleksandr Pevzner, John F Guzowski
No studies to date have examined whether immediate-early gene (IEG) activation is driven by context memory recall. To address this question, we utilized the context preexposure facilitation effect (CPFE) paradigm. In CPFE, animals acquire contextual fear conditioning through hippocampus-dependent rapid retrieval of a previously formed contextual representation. Despite differences in behavior, we did not find any difference in CA1 or CA3 IEG activity associated with this rapid recall phase when comparing context preexposed and non-pre-exposed groups...
January 2014: Learning & Memory
P J Fitzgerald, C R Pinard, M C Camp, M Feyder, A Sah, H C Bergstrom, C Graybeal, Y Liu, O M Schlüter, S G Grant, N Singewald, W Xu, A Holmes
Traumatic fear memories are highly durable but also dynamic, undergoing repeated reactivation and rehearsal over time. Although overly persistent fear memories underlie anxiety disorders, such as posttraumatic stress disorder, the key neural and molecular mechanisms underlying fear memory durability remain unclear. Postsynaptic density 95 (PSD-95) is a synaptic protein regulating glutamate receptor anchoring, synaptic stability and certain types of memory. Using a loss-of-function mutant mouse lacking the guanylate kinase domain of PSD-95 (PSD-95(GK)), we analyzed the contribution of PSD-95 to fear memory formation and retrieval, and sought to identify the neural basis of PSD-95-mediated memory maintenance using ex vivo immediate-early gene mapping, in vivo neuronal recordings and viral-mediated knockdown (KD) approaches...
July 2015: Molecular Psychiatry
Melissa S Monsey, Danielle M Gerhard, Lara M Boyle, Miguel A Briones, Ma'ayan Seligsohn, Glenn E Schafe
Curcumin, a yellow-pigment compound found in the popular Indian spice turmeric (Curcuma longa), has been extensively investigated for its anti-inflammatory, chemopreventative, and antidepressant properties. Here, we examined the efficacy of dietary curcumin at impairing the consolidation and reconsolidation of a Pavlovian fear memory, a widely studied animal model of traumatic memory formation in posttraumatic stress disorder (PTSD). We show that a diet enriched with 1.5% curcumin prevents the training-related elevation in the expression of the immediate early genes (IEGs) Arc/Arg3...
April 2015: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Jun-Jun Wang, Wen-Qing Yao, Yue-Jun Chen, Lan Ma, Ye-Zheng Tao
The intense associative memories that develop between cocaine-paired contexts and rewarding stimuli make addiction hard to cure by contributing to cocaine seeking and relapse. So it's of great importance to examine the neurobiological basis of addiction memory. Cocaine conditioned place preference (CPP) used in this study is a form of Pavlovian conditioning which can establish associations between drug and contextual factors. c-Fos and Zif268 are commonly used immediate early gene (IEG) makers to identify neurons that are activated after a stimulus or behavioral conditioning...
October 25, 2014: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Joanna L Workman, Melissa Y T Chan, Liisa A M Galea
Chronic stress or chronically high glucocorticoids attenuate adult hippocampal neurogenesis by reducing cell proliferation, survival, and differentiation in male rodents. Neurons are still produced in the dentate gyrus during chronically high glucocorticoids, but it is not known whether these new neurons are appropriately activated in response to spatial memory. Thus, the goal of this study was to determine whether immature granule neurons generated during chronically high glucocorticoids (resulting in a depressive-like phenotype) are differentially activated by spatial memory retrieval...
March 2015: Hippocampus
Dulcie A Vousden, Jonathan Epp, Hiroyuki Okuno, Brian J Nieman, Matthijs van Eede, Jun Dazai, Timothy Ragan, Haruhiko Bito, Paul W Frankland, Jason P Lerch, R Mark Henkelman
The ability to visualize behaviourally evoked neural activity patterns across the rodent brain is essential for understanding the distributed brain networks mediating particular behaviours. However, current imaging methods are limited in their spatial resolution and/or ability to obtain brain-wide coverage of functional activity. Here, we describe a new automated method for obtaining cellular-level, whole-brain maps of behaviourally induced neural activity in the mouse. This method combines the use of transgenic immediate-early gene reporter mice to visualize neural activity; serial two-photon tomography to image the entire brain at cellular resolution; advanced image processing algorithms to count the activated neurons and align the datasets to the Allen Mouse Brain Atlas; and statistical analysis to identify the network of activated brain regions evoked by behaviour...
July 2015: Brain Structure & Function
Sarah A Stern, Amy S Kohtz, Gabriella Pollonini, Cristina M Alberini
To treat cognitive disorders in humans, new effective therapies that can be easily delivered systemically are needed. Previous studies showed that a bilateral injection of insulin-like growth factor II (IGF-II) into the dorsal hippocampus of rats or mice enhances fear memories and facilitates fear extinction. Here, we report that, in mice, systemic treatments with IGF-II given before training significantly enhance the retention and persistence of several types of working, short-term and long-term memories, including fear conditioning, object recognition, object placement, social recognition, and spatial reference memory...
August 2014: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Mariah J Lelos, Mark A Good
Although episodic memory deficits are the most conspicuous cognitive change in patients with Alzheimer's disease (AD), patients also display alterations in emotional expression, including anxiety and impaired conditioned fear behaviours. The neural circuitry underlying emotional learning is known to involve the amygdala and hippocampus, although the precise impact of amyloid pathology on the interaction between these brain regions remains unclear. Recent evidence suggests that Tg2576 mice, which express a human amyloid precursor protein (APP) mutation associated with early-onset AD, demonstrate normal acquisition of conditioned freezing to auditory and contextual stimuli paired with footshock...
May 2014: European Journal of Neuroscience
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