Hippocampal Memory Recovery After Acute Stress: A Behavioral, Morphological and Molecular Study

Indexación: Scopus.Laboratory of Neuroplasticity and Neurogenetics, Department of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, Santiago, Chile, 2Laboratorio Farmacología del Comportamiento, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile, 3Department of Kinesiology, Faculty of Health Sciences, Universidad Católica del Maule, Talca, Chile, 4Facultad de Psicología, Universidad de Talca, Talca, Chile, 5Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, Chile, 6Escuela de Química y Farmacia, Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.This study was supported by the following grants: Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) 1120528 (JLF), Fondo Central de Investigación, Universidad de Chile ENL025/16 (JLF).Several studies have shown that a single exposure to stress may improve or impair learning and memory processes, depending on the timing in which the stress event occurs with relation to the acquisition phase. However, to date there is no information about the molecular changes that occur at the synapse during the stress-induced memory modification and after a recovery period. In particular, there are no studies that have evaluated—at the same time—the temporality of stress and stress recovery period in hippocampal short-term memory and the effects on dendritic spine morphology, along with variations in N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits. The aim of our study was to take a multidimensional approach to investigate concomitant behavioral, morphological and molecular changes induced by a single restraint stress exposure (2.5 h) and a recovery period of 6 and 24 h in rats. We found that acute stress elicited a reduced preference to explore an object placed in a novel position (a hippocampal-dependent task). These changes were accompanied by increased activity of LIM kinase I (LIMK; an actin-remodeling protein) and increased levels of NR2A subunits of NMDA receptors. After 6 h of recovery from stress, rats showed similar preference to explore an object placed in a novel or familiar position, but density of immature spines increased in secondary CA1 apical dendrites, along with a transient rise in GluA2 AMPA receptor subunits. After 24 h of recovery from stress, the animals showed a preference to explore an object placed in a novel position, which was accompanied by a normalization of NMDA and AMPA receptor subunits to control values. Our data suggest that acute stress produces reversible molecular and behavioral changes 24 h after stress, allowing a full reestablishment of hippocampal-related memory. Further studies need to be conducted to deepen our understanding of these changes and their reciprocal interactions.Adaptive stress responses are a promising avenue to develop interventions aiming at restoring hippocampal function impaired by repetitive stress exposure. © 2018 Aguayo, Tejos-Bravo, Díaz-Véliz, Pacheco, García-Rojo, Corrales, Olave, Aliaga, Ulloa, Avalos, Román-Albasini, Rojas and Fiedler.https://www.frontiersin.org/articles/10.3389/fnmol.2018.00283/ful

Hippocampal Infusion of Zeta Inhibitory Peptide Impairs Recent, but Not Remote, Recognition Memory in Rats.

Spatial memory in rodents can be erased following the infusion of zeta inhibitory peptide (ZIP) into the dorsal hippocampus via indwelling guide cannulas. It is believed that ZIP impairs spatial memory by reversing established late-phase long-term potentiation (LTP). However, it is unclear whether other forms of hippocampus-dependent memory, such as recognition memory, are also supported by hippocampal LTP. In the current study, we tested recognition memory in rats following hippocampal ZIP infusion. In order to combat the limited targeting of infusions via cannula, we implemented a stereotaxic approach for infusing ZIP throughout the dorsal, intermediate, and ventral hippocampus. Rats infused with ZIP 3-7 days after training on the novel object recognition task exhibited impaired object recognition memory compared to control rats (those infused with aCSF). In contrast, rats infused with ZIP 1 month after training performed similar to control rats. The ability to form new memories after ZIP infusions remained intact. We suggest that enhanced recognition memory for recent events is supported by hippocampal LTP, which can be reversed by hippocampal ZIP infusion

Adaptive cancelation of self-generated sensory signals in a whisking robot

Sensory signals are often caused by one's own active movements. This raises a problem of discriminating between self-generated sensory signals and signals generated by the external world. Such discrimination is of general importance for robotic systems, where operational robustness is dependent on the correct interpretation of sensory signals. Here, we investigate this problem in the context of a whiskered robot. The whisker sensory signal comprises two components: one due to contact with an object (externally generated) and another due to active movement of the whisker (self-generated). We propose a solution to this discrimination problem based on adaptive noise cancelation, where the robot learns to predict the sensory consequences of its own movements using an adaptive filter. The filter inputs (copy of motor commands) are transformed by Laguerre functions instead of the often-used tapped-delay line, which reduces model order and, therefore, computational complexity. Results from a contact-detection task demonstrate that false positives are significantly reduced using the proposed scheme

Hippocampus-dependent emergence of spatial sequence coding in retrosplenial cortex.

Retrosplenial cortex (RSC) is involved in visuospatial integration and spatial learning, and RSC neurons exhibit discrete, place cell-like sequential activity that resembles the population code of space in hippocampus. To investigate the origins and population dynamics of this activity, we combined longitudinal cellular calcium imaging of dysgranular RSC neurons in mice with excitotoxic hippocampal lesions. We tracked the emergence and stability of RSC spatial activity over consecutive imaging sessions. Overall, spatial activity in RSC was experience-dependent, emerging gradually over time, but, as seen in the hippocampus, the spatial code changed dynamically across days. Bilateral but not unilateral hippocampal lesions impeded the development of spatial activity in RSC. Thus, the emergence of spatial activity in RSC, a major recipient of hippocampal information, depends critically on an intact hippocampus; the indirect connections between the dysgranular RSC and the hippocampus further indicate that hippocampus may exert such influences polysynaptically within neocortex

SOVEREIGN: An Autonomous Neural System for Incrementally Learning Planned Action Sequences to Navigate Towards a Rewarded Goal

How do reactive and planned behaviors interact in real time? How are sequences of such behaviors released at appropriate times during autonomous navigation to realize valued goals? Controllers for both animals and mobile robots, or animats, need reactive mechanisms for exploration, and learned plans to reach goal objects once an environment becomes familiar. The SOVEREIGN (Self-Organizing, Vision, Expectation, Recognition, Emotion, Intelligent, Goaloriented Navigation) animat model embodies these capabilities, and is tested in a 3D virtual reality environment. SOVEREIGN includes several interacting subsystems which model complementary properties of cortical What and Where processing streams and which clarify similarities between mechanisms for navigation and arm movement control. As the animat explores an environment, visual inputs are processed by networks that are sensitive to visual form and motion in the What and Where streams, respectively. Position-invariant and sizeinvariant recognition categories are learned by real-time incremental learning in the What stream. Estimates of target position relative to the animat are computed in the Where stream, and can activate approach movements toward the target. Motion cues from animat locomotion can elicit head-orienting movements to bring a new target into view. Approach and orienting movements are alternately performed during animat navigation. Cumulative estimates of each movement are derived from interacting proprioceptive and visual cues. Movement sequences are stored within a motor working memory. Sequences of visual categories are stored in a sensory working memory. These working memories trigger learning of sensory and motor sequence categories, or plans, which together control planned movements. Predictively effective chunk combinations are selectively enhanced via reinforcement learning when the animat is rewarded. Selected planning chunks effect a gradual transition from variable reactive exploratory movements to efficient goal-oriented planned movement sequences. Volitional signals gate interactions between model subsystems and the release of overt behaviors. The model can control different motor sequences under different motivational states and learns more efficient sequences to rewarded goals as exploration proceeds.Riverside Reserach Institute; Defense Advanced Research Projects Agency (N00014-92-J-4015); Air Force Office of Scientific Research (F49620-92-J-0225); National Science Foundation (IRI 90-24877, SBE-0345378); Office of Naval Research (N00014-92-J-1309, N00014-91-J-4100, N00014-01-1-0624, N00014-01-1-0624); Pacific Sierra Research (PSR 91-6075-2

Short-term plasticity as cause-effect hypothesis testing in distal reward learning

Asynchrony, overlaps and delays in sensory-motor signals introduce ambiguity as to which stimuli, actions, and rewards are causally related. Only the repetition of reward episodes helps distinguish true cause-effect relationships from coincidental occurrences. In the model proposed here, a novel plasticity rule employs short and long-term changes to evaluate hypotheses on cause-effect relationships. Transient weights represent hypotheses that are consolidated in long-term memory only when they consistently predict or cause future rewards. The main objective of the model is to preserve existing network topologies when learning with ambiguous information flows. Learning is also improved by biasing the exploration of the stimulus-response space towards actions that in the past occurred before rewards. The model indicates under which conditions beliefs can be consolidated in long-term memory, it suggests a solution to the plasticity-stability dilemma, and proposes an interpretation of the role of short-term plasticity.Comment: Biological Cybernetics, September 201