Abstract
GluA2-containing AMPA receptors and their association with protein kinase M zeta (PKMζ) and post-synaptic density-95 (PSD-95) are important for learning, memory and synaptic plasticity processes. Here we investigated these synaptic markers in the context of an acute 1h platform stress, which can disrupt spatial memory retrieval for a short-term memory on the object placement task and long-term memory retrieval on a well-learned radial arm maze task. Acute stress increased serum corticosterone and elevated the expression of synaptic PKMζ while decreasing synaptic GluA2. Using co-immunoprecipitation, we found that this stressor promotes the clustering of GluA2, PKMζ and PSD-95, which is consistent with effects reported from overexpression of PKMζ in cell culture. Because PKMζ overexpression has also been shown to induce spine maturation in culture, we examined how stress impacts synaptic markers within changing spines across various hippocampal subfields. To achieve this, we employed a new technique combining Golgi staining and immmunohistochemistry to perform 3D reconstruction of tertiary dendrites, which can be analyzed for differences in spine types and the colocalization of synaptic markers within these spines. In CA1, stress increased the densities of long-thin and mushroom spines and the colocalization of GluA2/PSD-95 within these spines. Conversely, in CA3, stress decreased the densities of filopodia and stubby spines, with a concomitant reduction in the colocalization of GluA2/PSD-95 within these spines. In the outer molecular layer (OML) of the dentate gyrus (DG), stress increased both stubby and long-thin spines, together with greater GluA2/PSD-95 colocalization. These data reflect the rapid effects of stress on inducing morphological changes within specific hippocampal subfields, highlighting a potential mechanism by which stress can modulate memory consolidation and retrieval.
Highlights
The ability of stress paradoxically either to enhance or impair memory consolidation and retrieval is a well-documented phenomenon [1]
We address the following questions: How are clusters of key synaptic markers affected by an acute physiological stress? How are dendritic spines affected by this stress across hippocampus subfields? how are these synaptic protein clusters participating in stress-induced changes in spine morphology?
In an effort to further understand the changing spine density and synaptic marker expression induced in various hippocampal subfields after stress, we focused on the outer molecular layer of the dentate gyrus
Summary
The ability of stress paradoxically either to enhance or impair memory consolidation and retrieval is a well-documented phenomenon [1]. The hippocampus, an area widely known for its role in learning and memory processing, is vulnerable to stress-induced neuroendocrine responses affecting structure and function [2]. Mild stressors induce enhanced performance for spatial and fear conditioning tasks [5], while severe stressors produce impairments in memory function irrespective of whether the stress is acute or chronic [6]. These effects are associated in part with changes in hippocampal neuronal structure and spine density. The mechanisms by which stress induces these changes in structure and function of the hippocampus are largely unknown
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