Stress suppresses and learning induces plasticity in CA3 of rat hippocampus: A three-dimensional ultrastructural study of thorny excrescences and their postsynaptic densities

Abstract

Abstract-Chronic stress and spatial training have been proposed to affect hippocampal structure and function in opposite ways. Previous morphological studies that addressed structural changes after chronic restraint stress and spatial training were based on two-dimensional morphometry which does not allow a complete morphometric characterisation of synaptic features. Here, for the first time in such studies, we examined these issues by using three-dimensional (3-D) reconstructions of electron microscope images taken from thorny excrescences of hippocampal CA3 pyramidal cells. Ultrastructural alterations in postsynaptic densities (PSDs) of thorny excrescences receiving input from mossy fibre boutons were also determined, as were changes in numbers of multivesicular bodies (endosome-like structures) within thorny excrescences and dendrites. Quantitative 3-D data demonstrated retraction of thorny excrescences after chronic restraint stress which was reversed after water maze training, whilst water maze training alone increased thorny excrescence volume and number of thorns per thorny excrescence. PSD surface area was unaffected by restraint stress but water maze training increased both number and area of PSDs per thorny excrescence. In restrained rats that were water maze trained PSD volume and surface area increased significantly. The proportion of perforated PSDs almost doubled after water maze training and restraint stress. Numbers of endosome-like structures in thorny excrescences decreased after restraint stress and increased after water maze training. These findings demonstrate that circuits involving contacts between mossy fibre terminals and CA3 pyramidal cells at stratum lucidum level are affected conversely by water maze training and chronic stress, confirming the remarkable plasticity of CA3 dendrites. They provide a clear illustration of the structural modifications that occur after life experiences noted for their different impact on hippocampal function. © 2005 Published by Elsevier Ltd on behalf of IBRO.

Hippocampal neuroplasticity induced by early-life stress: Functional and molecular aspects

“…Chronic stress may contribute to deficits in hippocampus-dependent learning and memory [92,135] including those found during senescence [76,100,153]. In addition, chronic stress in adults negatively affects long-term potentiation (LTP) in hippocampal subfields [109,3], including the commissural-associational projections in field CA3 [109].…”

Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multi-modal stress

“…[28][29][30] We used wide-field imaging followed by 3-dimensional deconvolution tomography, a method enabling analysis of hundreds of thousands of synapses. 43,44 We sampled systematically dorsal (septal) and ventral (temporal) hippocampus, and compared the effects of restraint and multimodal stresses (Figures 2a and d).…”

“…The postsynaptic density 95 protein (PSD-95), which is localized primarily to dendritic spine heads, was used as a reliable marker for mature synapses. [28][29][30] Mice were perfused immediately after the stress, and brains were postfixed and processed for immunohistochemistry as described in previous studies. 31 Briefly, brains were sectioned coronally (for dorsal hippocampus) or horizontally into 20 μm thick slices.…”

Regulation of Structural Plasticity and Neurogenesis during Stress and Diabetes; Protective Effects of Glucocorticoid Receptor Antagonists

“…Chronic stress or experimentally increased corticosterone concentrations induce retraction of the apical dendrites of the CA3 and, to a lesser extent, of CA1 pyramidal cells and dentate granule cells [6,27,28]. Alterations in CA3 synapses and in the morphology of their mossy fiber terminals have also been described [27][28][29]. These changes in neuronal morphology are likely to contribute to various cognitive deficits occurring as a result of chronic stress exposure.…”

“…The most thoroughly documented stress-induced structural change is the dendritic reorganization that occurs parallel to the loss of spines and synapses and together with alterations in postsynaptic densities, suggesting general changes in neuronal connectivity. Chronic stress or experimentally increased corticosterone concentrations induce retraction of the apical dendrites of the CA3 and, to a lesser extent, of CA1 pyramidal cells and dentate granule cells [6,27,28]. Alterations in CA3 synapses and in the morphology of their mossy fiber terminals have also been described [27][28][29].…”