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

Felipe Ignacio Aguayo,Macarena Tejos-Bravo,Wladimir Corrales,Paulina S Rojas,Esteban Aliaga,Gabriela Díaz-Véliz,Felipe Antonio Olave,Aníbal Pacheco,Jenny Lucy Fiedler,Ana M Avalos,José L Ulloa,Gonzalo García-Rojo,Luciano Román-Albasini

doi:10.3389/fnmol.2018.00283

Abstract

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.

Highlights

Acute stress exposure may modify memory processes in several ways, depending on the extent, intensity and timing in which the stress event occurs (Joels et al, 2006)
Considering all these antecedents, our aim was to combine behavioral, morphological and molecular approaches to investigate the effect of a single acute stress exposure and recovery period on hippocampus-associated memory; changes that may be related to variations in dendritic spine density, along with variations in the activity of pathways related to actin dynamics and the levels of amino-3-hydroxy-5-methyl-4isoxazolepropionic acid (AMPA) receptor and NMDA receptor subunits
After stress, we observed a strong reduction in hippocampal short-term memory, change that was coincident with a rise in actin-dynamics and NR2A subunit levels of NMDA receptors, but not with an evident change in spine morphology of CA1 neurons

Summary

Introduction

Acute stress exposure may modify memory processes in several ways, depending on the extent, intensity and timing in which the stress event occurs (Joels et al, 2006). Converging with these evidences, another study found that restraint stress (1 h) elicited impaired memory acquisition, consolidation and retrieval in rodents, as assessed with object-recognition and object-location tasks (OLT; Li et al, 2012) These evidences suggest that acute stress may modulate hippocampus functioning by changing synaptic strength, thereby impacting cognitive process, including learning and memory (Middei et al, 2014). In rodents, a brief neck restraint stress facilitates LTP, but suppresses long-lasting depression (LTD) in the DG; effect that was related to the activation of both glucocorticoid and mineralocorticoid receptors (Spyrka et al, 2011) These data seem to be discordant, it is important to highlight that each type of stressor may influence particular brain circuits by modulating synaptic plasticity, which influences the animal’s behavior

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