Detection of novelty, but not memory of spatial habituation, is associated with an increase in phophorylated cAMP response element-binding protein levels in the hippocampus

There is a growing body of evidence showing that the formation of associative memories is associated with an increase in phosphorylated cAMP response element-binding protein (pCREB) levels. We recently reported that pCREB level increased in the rat hippocampus after an exploration to a novel environment. In the present work, we studied whether this increment in CREB activation is associated with the formation of memory of habituation to a novel environment or with the detection of novelty. Rats were submitted to consecutive open field sessions at 3 h intervals. Hippocampal pCREB level measurement, performed 1 hour after each training-sessions, revealed that: a) it did not increase when rats explored a familiar environment; b) it did not increase after a re-exposure that improves the memory of habituation; c) it increased after a brief novel exploration unable to form memory of habituation and d) it also increased in amnesic rats for spatial habituation. Taken as a whole, our results suggest that the elevated  pCREB level after a single open field exploration is not associated with the memory formation of habituation. It is indeed associated with the detection of a novel environment.Fil: Winograd, Milena Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Viola, Haydee Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

Behavioral Tagging: A Translation of the Synaptic Tagging and Capture Hypothesis

Similar molecular machinery is activated in neurons following an electrical stimulus that induces synaptic changes and after learning sessions that trigger memory formation. Then, to achieve perdurability of these processes protein synthesis is required for the reinforcement of the changes induced in the network. The synaptic tagging and capture theory provided a strong framework to explain synaptic specificity and persistence of electrophysiological induced plastic changes. Ten years later, the behavioral tagging hypothesis (BT) made use of the same argument, applying it to learning and memory models. The hypothesis postulates that the formation of lasting memories relies on at least two processes: the setting of a learning tag and the synthesis of plasticity related proteins, which once captured at tagged sites allow memory consolidation. BT explains how weak events, only capable of inducing transient forms of memories, can result in lasting memories when occurring close in time with other behaviorally relevant experiences that provide proteins. In this review, we detail the findings supporting the existence of BT process in rodents, leading to the consolidation, persistence, and interference of a memory. We focus on the molecular machinery taking place in these processes and describe the experimental data supporting the BT in humans.Fil: Moncada, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Ballarini, Fabricio Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Viola, Haydee Ana Maria. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

Redefining Single-Trial Memories in the Honeybee

Research on honeybee memory has led to a widely accepted model in which a single pairing of an odor stimulus with sucrose induces memories that are independent of protein synthesis but is unable to form protein-synthesis-dependent long-term memory (LTM). The latter is said to arise only after three or more pairings of odor and sucrose. Here, we show that this model underestimates the capacity of the bee brain to form LTMs after a unique appetitive experience. Using state-of-the art conditioning setups and individual-based analyses of conditioned responses, we found that protein-synthesis-dependent memories are formed already 4 h after the single conditioning trial and persist even 3 days later. These memories (4 h, 24 h, and 72 h) exhibit different dependencies on transcription and translation processes. Our results thus modify the traditional view of onetrial memories in an insect with a model status for memory research.Fil: Villar, María Eugenia. Université de Toulouse; Francia. Centre National de la Recherche Scientifique; Francia. Universite de la Mediterranee. Institut Universitaire de France; FranciaFil: Marchal, Paul. Université de Toulouse; Francia. Centre National de la Recherche Scientifique; Francia. Universite de la Mediterranee. Institut Universitaire de France; FranciaFil: Viola, Haydee Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Giurfa, Martín. Université de Toulouse; Francia. Centre National de la Recherche Scientifique; Francia. Fujian Agriculture and Forestry University; Chin

Novelty during a late postacquisition time window attenuates the persistence of fear memory

Learning to avoid threats in the environment is highly adaptive. However, sometimes a dysregulation of fear memories processing may underlie fear-related disorders. Despite recent advances, a major question of how to effectively attenuate persistent fear memories in a safe manner remains unresolved. Here we show experiments employing a behavioural tool to target a specific time window after training to limit the persistence of a fear memory in rats. We observed that exposure to a novel environment 11 h after an inhibitory avoidance (IA) training that induces a long-lasting memory, attenuates the durability of IA memory but not its formation. This effect is time-restricted and not seen when the environment is familiar. In addition, novelty-induced attenuation of IA memory durability is prevented by the intrahippocampal infusion of the CaMKs inhibitor KN-93. This new behavioural approach which targets a specific time window during late memory consolidation, might represent a new tool for reducing the durability of persistent fear memories.Fil: Katche, Cynthia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Tomaiuolo, Micol. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Dorman, Guido. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Medina, Jorge Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Viola, Haydee Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentin

Spatial object recognition memory formation under acute stress

Stress is known to have a critical impact on memory processes. In the present work, we focus on the effects of an acute stress event closely associated to an unrelated learning task. Here, we show that acute stress (elevated platform [EP] session) experienced 1 hr after a weak spatial object recognition (SOR) training, which only induces a short-term memory (STM), promoted the formation of SOR-long term memory (SOR-LTM) in rats. The effect induced by stress was dependent on the activation of glucocorticoid- and mineralocorticoid-receptors, brain-derived neurotrophic factor (BDNF) and protein synthesis in the dorsal hippocampus. In contrast, EP after a strong SOR impaired SOR-LTM probably by interfering with the use of necessary resources. Moreover, we show that the EP session before training induced anterograde interference, which it was not reversed by a subsequent exposure to an open field. Our findings provide novel insights into the impact of stress on LTM formation in rodents and they are discussed under the behavioral analogue of the synaptic tagging and capture hypothesis.Fil: Lopes Da Cunha, Pamela Johanna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Villar, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Ballarini, Fabricio Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Tintorelli, Ramiro Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Viola, Haydee Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentin

Inhibitory learning of phototaxis by honey bees in a passive-avoidance task

Honeybees are a standard model for the study of appetitive learning and memory. Yet, fewer attempts have been performedto characterize aversive learning and memory in this insect and uncover its molecular underpinnings. Here, wetook advantage of the positive phototactic behavior of bees kept away from the hive in a dark environment and establisheda passive-avoidance task in which they had to suppress positive phototaxis. Bees placed in a two-compartment box learned toinhibit spontaneous attraction to a compartment illuminated with blue light by associating and entering into that chamberwith shock delivery. Inhibitory learning resulted in an avoidance memory that could be retrieved 24 h after training andthat was specific to the punished blue light. It was mainly operant but involves a Pavlovian component linking the blue lightQ4 and the shock. Coupling and conditioning with transcriptional analyses in key areas of the brain showed that inhibitorylearning of phototaxis leads to an up-regulation of the dopaminergic receptor gene Amdop1 in the calyces of the mushroombodies, consistently with the role of dopamine signaling in different forms of aversive learning in insects. Our results thusintroduce new perspectives for uncovering further cellular and molecular underpinnings of aversive learning and memoryin bees. Overall, they represent an important step toward comparative learning studies between the appetitive and the aversiveframeworks.Fil: Marchal, P.. Centre National de la Recherche Scientifique; FranciaFil: Villar, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Heiyang, Geng. Centre National de la Recherche Scientifique; FranciaFil: Arrufat, Patrick. Centre National de la Recherche Scientifique; FranciaFil: Combe, Maud. Centre National de la Recherche Scientifique; FranciaFil: Viola, Haydee Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Massou, Isabelle. Centre National de la Recherche Scientifique; FranciaFil: Giurfa, Martín. Centre National de la Recherche Scientifique; Franci

Spatial-Memory Formation After Spaced Learning Involves ERKs1/2 Activation Through a Behavioral-Tagging Process

The superiority of spaced over massed learning is an established fact in the formation of long-term memories (LTM). Here we addressed the cellular processes and the temporal demands of this phenomenon using a weak spatial object recognition (wSOR) training, which induces short-term memories (STM) but not LTM. We observed SOR-LTM promotion when two identical wSOR training sessions were spaced by an inter-trial interval (ITI) ranging from 15 min to 7 h, consistently with spaced training. The promoting effect was dependent on neural activity, protein synthesis and ERKs1/2 activity in the hippocampus. Based on the “behavioral tagging” hypothesis, which postulates that learning induces a neural tag that requires proteins to induce LTM formation, we propose that retraining will mainly retag the sites initially labeled by the prior training. Thus, when weak, consecutive training sessions are experienced within an appropriate spacing, the intracellular mechanisms triggered by each session would add, thereby reaching the threshold for protein synthesis required for memory consolidation. Our results suggest in addition that ERKs1/2 kinases play a dual role in SOR-LTM formation after spaced learning, both inducing protein synthesis and setting the SOR learning-tag. Overall, our findings bring new light to the mechanisms underlying the promoting effect of spaced trials on LTM formation.Fil: Tintorelli, Ramiro Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Budriesi, Pablo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Villar, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Marchal, Paul. Université de Toulouse; FranciaFil: Lopes Da Cunha, Pamela Johanna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Correa, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Giurfa, Martín. Université de Toulouse, Francia; FranciaFil: Viola, Haydee Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

The tagging and capture hypothesis from synapse to memory

The synaptic tagging and capture theory (STC) was postulated by Frey and Morris in 1997 and provided a strong framework to explain how to achieve synaptic specificity and persistence of electrophysiological-induced plasticity changes. Ten years later, the same argument was applied on learning and memory models to explain the formation of long-term memories, resulting in the behavioral tagging hypothesis (BT). These hypotheses are able to explain how a weak event that induces transient changes in the brain can establish long-lasting phenomena through a tagging and capture process. In this framework, it was postulated that the weak event sets a tag that captures plasticity-related proteins/products (PRPs) synthesized by an independent strong event. The tagging and capture processes exhibit symmetry, and therefore, PRPs can be captured if they are synthesized either before or after the setting of the tag. In summary, the hypothesis provides a wide framework that gives a solid explanation of how lasting changes occur and how the interaction between different events leads to promotion, reinforcement, or impairment of such changes. In this chapter, we will summarize the postulates of STC hypothesis, the common features between synaptic plasticity and memory, as well as a detailed compilation of the findings supporting the existence of BT process. At the end, we pose some questions related to BT mechanism and LTM formation, which probably will be answered in the near future.Fil: Viola, Haydee Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Ballarini, Fabricio Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Martinez, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Moncada, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; Argentina. Leibniz - Institut für Neurobiologie; Alemani

Persistence of Spatial Memory Induced by Spaced Training Involves a Behavioral-Tagging Process

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. The protocol consisted of a first strong training session that induced LTM formation (tested 1 day after training), but not LTM persistence (tested 7 or 14 days after training); and a second weak training session that promoted memory persistence when applied 1 day, but not 7 days, after the first training. We propose that the promotion of memory persistence is based on the Behavioral Tagging (BT) mechanism operating when the memory trace is retrieved. BT involves the setting of a tag induced by learning which gives rise to input selectivity, and the use of plasticity-related proteins (PRPs) to establish the mnemonic trace. We postulate that retraining will mainly retag the sites initially activated by the original learning, where the PRPs needed for memory expression and/or induced by retrieval would be used to maintain a persistent mnemonic trace. 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.Fil: Correa, Julieta Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Tintorelli, Ramiro Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Budriesi, Pablo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Viola, Haydee Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentin