Acute Physiological Stress Promotes Clustering of Synaptic Markers and Alters Spine Morphology in the Hippocampus

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.

Overexpression of Protein Kinase Mζ in the Prelimbic Cortex Enhances the Formation of Long-Term Fear Memory

“…In addition, the present study provides in vivo evidence that PKMζ overexpression is sufficient to elicit the distribution of plasticity-related proteins and promote long-term memoryassociated alterations of plasticity-related proteins. Our results are consistent with previous in vitro studies that PKMζ overexpression is sufficient to produce the distribution of GluA2 and postsynaptic density-95 and alterations of the morphology and function of dendrite spines (Ron et al, 2012;Sebastian et al, 2013). However, the conclusion of the causal role of PKMζ in the regulation of GluA2 trafficking during memory consolidation should be made with caution.…”

Social Buffering Prevents Stress-Induced Decreases in Dendritic Length, Branching in Dentate Granule Cells and Hippocampus-Related Memory Performance

“…Moreover, we found that such a stressor regimen caused significant decreases in dendritic spine density in dendrites of the granule cells in the anterior (or dorsal) dentate gyrus at 6 hours after the conclusion of the stressor regimen. Although chronic stress has been known to produce long-lasting dendritic atrophy in hippocampus [38], a 1-hr platform stress was also reported to cause immediate morphological changes in hippocampus [39]. In parallel with the latter report, our findings indicated that a robust stressor may indeed render morphological changes in the existing granule cells in hippocampal dentate gyrus.…”

Lack of presynaptic interaction between glucocorticoid and CB1 cannabinoid receptors in GABA- and glutamatergic terminals in the frontal cortex of laboratory rodents

“…As our knowledge on subacute (genomic) and/or post-synaptic modulation of synaptic plasticity by corticosteroids is greatly expanding (Jo€ els et al, 2012;Maggio and Segal, 2012;Sebastian et al, 2013), we asked now if corticosteroids can also serve as fast direct presynaptic neuromodulators, either on their own or involving the CB 1 cannabinoid receptor (CB 1 R).…”

“…Studies on neural cell lines and primary cell cultures revealed the complex nature by which McRs and GcRs can trigger spatiotemporally distinct genomic and nongenomic responses, which can lead to changes in the expression and the clustering of pre-and post-synaptic proteins as well as to alterations in dendritic spine morphology (Chatterjee and Sikdar, 2014;Morsink et al, 2006;Sebastian et al, 2013). Of note, dendritic degeneration also occurs in vivo, as documented in the layers C]glutamate, and the lack of dexamethasone effect is unchanged in the CB 1 R KO mice as compared to the WT littermates.…”