1,721,036 research outputs found
Structural plasticity of the social brain:Social stress-induced adaptations in dendritic remodeling and behavior
Get PDFPsychosocial stressors are frequently the cause of psychopathologies like anxiety and depression in humans. We tried to explore in rat social stress models how individual personality and social stress affect neuronal structure in the brain and how this relates to the behavioral and physiological stress response. My research primarily focuses on the hippocampus, amygdala and prefrontal cortex, as brain regions involved in the regulation of stress response. As stress models we used repeated social defeat and stress of chronic subordination in semi-natural mixed-sex rat colonies.We demonstrated that hippocampal neurons are shrinking after social stress whereas neurons in the amygdala become larger in socially stressed rats. A surprising finding was that this neuronal plasticity was observed in both winners and losers despite their differential behavioral response. In the semi-natural colonies our male rats, offspring from rats originally caught in the wild, rapidly installed of a dominance hierarchy. The difference in hierarchical rank dictated the physiological and neurobiological differences among dominant and subordinate rats. We further introduced the colony-intruder paradigm, where highly resilient rats were defeated by the males in the colony, resulting in long-term alterations in the cardiovascular response. In addition, we examined personality as a risk factor in susceptibility to develop stress-related psychopathologies. This showed differential structural plasticity in defeated proactive and reactive individuals. Connecting these alterations with the underpinnings of structural remodeling will contribute to a better understanding of the pathogenesis of stress and hopefully contribute to better treatment of psychological disorders
Modulation of different states of anxiety-like behavior by chronic stress
No full textRecent studies have identified putative cellular correlates of stress-induced amygdalar plasticity underlying anxiety-like behavior. Chronic Immobilization Stress (CIS), but not Chronic Unpredictable Stress (CUS), has been reported to induce dendritic remodeling in the Basolateral Amygdala (BLA). The BLA is also important for consolidation of anxiety in the elevated plus-maze, which is manifested as increased open-arm avoidance on re-exposure to the maze. The authors found that CIS, unlike CUS, facilitated anxiety-like behavior in the plus-maze and this occluded further increase in anxiety when CIS rats were re-exposed to the maze 72 hr after the first trial. However, both CUS and control rats exhibited consolidation between trials. Thus, consolidation of anxiety may share common cellular mechanisms that also underlie chronic stress-induced structural plasticity in the amygdala
Interventions after acute stress prevent its delayed effects on the amygdala
No full textStress is known to elicit contrasting patterns of plasticity in the amygdala and hippocampus. While chronic stress leads to neuronal atrophy in the rodent hippocampus, it has the opposite effect in the basolateral amygdala (BLA). Further, even a single episode of acute stress is known to elicit delayed effects in the amygdala. For example, 2 h of immobilisation stress has been shown to cause a delayed increase in dendritic spine density on BLA principal neurons 10 days later in young rats. This is paralleled by higher anxiety-like behaviour at the same delayed time point. This temporal build-up of morphological and behavioural effects 10 days later, in turn, provides a stress-free time window of intervention after exposure to acute stress. Here, we explore this possibility by specifically testing the efficacy of an anxiolytic drug in reversing the delayed effects of acute immobilisation stress. Oral gavage of diazepam 1 h after immobilisation stress prevented the increase in anxiety-like behaviour on the elevated plus-maze 10 days later. The same post-stress intervention also prevented delayed spinogenesis in the BLA 10 days after acute stress. Surprisingly, gavage of only the vehicle also had a protective effect on both the behavioural and synaptic effects of stress 10 days later. Vehicle gavage was found to trigger a significant rise in corticosterone levels that was comparable to that elicited by acute stress. This suggests that a surge in corticosterone levels, caused by the vehicle gavage 1 h after acute stress, was capable of reversing the delayed enhancing effects of stress on anxiety-like behaviour and BLA synaptic connectivity. These findings are consistent with clinical reports on the protective effects of glucocorticoids against the development of symptoms of post-traumatic stress disorder. Taken together, these results reveal strategies, targeted 1 h after stress, which can prevent the delayed effects of a brief exposure to a severe physical stressor
Biophysical correlates of intrinsic and stress-induced morphological variability in lateral amygdaloid neurons: A computational study
No full textMorphological and physiological characteristics of neurons located in the dorsolateral and two ventral subdivisions of the lateral amygdala (LA) have been compared in order to differentiate their roles in the formation and storage of fear memories (Alphs et al, SfN abs 623.1, 2003). Briefly, in these populations, significant differences are observed in input resistance, membrane time constant, firing frequency, dendritic tortuosity, numbers of primary dendrites, dendritic segments and dendritic nodes..
Timing is everything: differential effects of chronic stress on fear extinction
No full textRationale
Stress disorders cause abnormal regulation of fear-related behaviors. In most rodent models of these effects, stress was administered before fear conditioning, thereby assessing its impact on both the formation and extinction of fear memories, not the latter alone. Here, we dissociated the two processes by also administering stress after fear conditioning, and then compared how pre-conditioning versus post-conditioning exposure to chronic stress affects subsequent acquisition and recall of fear extinction.
Methods
Male Wistar rats were subjected to chronic immobilization stress (2 h/day, 10 days); the morphological effects of which were analyzed using modified Golgi-Cox staining across brain areas mediating the formation and extinction of fear memories. Separate groups of rats underwent fear conditioning followed by acquisition and recall of extinction, wherein stress was administered either before or after fear conditioning.
Results
When fear memories were formed after chronic stress, both acquisition and retrieval of extinction was impaired. Strikingly, these deficits were absent when fear memories were formed before the same stress. Chronic stress also reduced dendritic spine density in the infralimbic prefrontal cortex, but enhanced it in the basolateral amygdala.
Conclusion
Chronic stress, administered either before or after fear learning, had distinct effects on the acquisition and recall of fear extinction memories. Stress also strengthened the structural basis of synaptic connectivity in the amygdala, but weakened it in the prefrontal cortex. Thus, despite eliciting a specific pattern of brain region-specific morphological changes, the timing of the same stress gave rise to strikingly different behavioral effects on the extinction of fear
Marble burying as a test of the delayed anxiogenic effects of acute immobilisation stress in mice
No full textA majority of rodent studies characterizing the anxiogenic effects of stress have utilized exploration-based models, such as the elevated plus-maze. An alternative strategy has relied on ethologically natural behavior such as defensive burying. One such paradigm, marble burying, has proven to be an effective behavioral assay of the anxiolytic effects of pharmacological manipulations, and of genetically modified mouse models. Relatively little, however, is known about the sensitivity of this test in assessing the anxiogenic effects of stress. Most of the earlier reports have examined the immediate, but not more long-term, effects of pharmacological or environmental manipulations in mice. Hence, we used the marble burying test to examine if acute immobilization stress leads to enhanced anxiety-like behavior in C57Bl/6 mice if the test is employed with a significant time delay. We find this test to be sensitive enough to detect the anxiogenic effects even 10 days after a single episode of 2-h immobilization stress. Our results suggest that the marble burying test could serve as a useful behavioral paradigm for not only estimating the gradual progression of the anxiogenic impact of stress over time, but also raises the possibility of using the temporal delay after stress to test the potential efficacy of post-stress interventions with anxiolytic drugs
Computational analysis of the impact of chronic stress on intrinsic and synaptic excitability in the hippocampus
No full textDendritic atrophy and impaired Long-Term Synaptic Potentiation (LTP) are hallmarks of chronic stress-induced plasticity in the hippocampus. It has been hypothesized that these disparate structural and physiological correlates of stress lead to hippocampal dysfunction by reducing postsynaptic dendritic surface, thereby adversely affecting the availability of synaptic inputs and suppressing LTP. Here we examine the validity of this framework using biophysical models of hippocampal CA3 pyramidal neurons. To statistically match with the experimentally observed region specificity of stress-induced atrophy, we use an algorithm to systematically prune three-dimensional reconstructions of CA3 pyramidal neurons. Using this algorithm, we build a biophysically realistic computational model to analyze the effects of stress on intrinsic and synaptic excitability. We find that stress-induced atrophy of CA3 dendrites leads to an increase in input resistance, which depends exponentially on the percentage of neuronal atrophy. This increase translates directly into higher spiking frequencies in response to both somatic current injections and synaptic inputs at various locations along the dendritic arbor. Remarkably, we also find that the dendritic regions that manifest atrophy-induced synaptic hyperexcitability are governed by the region specificity of the underlying dendritic atrophy. Coupled with experimentally observed modulation of N-methyl-D-aspartate receptor currents, such hyperexcitability could tilt the balance of plasticity mechanisms in favor of synaptic potentiation over depression. Thus paradoxically, our results suggest that stress may impair hippocampal learning and memory, not by directly inhibiting LTP, but because of stress-induced facilitation of intrinsic and synaptic excitability and the consequent imbalance in bidirectional synaptic plasticity
Stress Elicits Contrasting Effects on the Structure and Number of Astrocytes in the Amygdala versus Hippocampus
No full textStress causes divergent patterns of structural and physiological plasticity in the hippocampus versus amygdala. However, a majority of earlier studies focused primarily on neurons. Despite growing evidence for the importance of glia in health and disease, relatively little is known about how stress affects astrocytes. Further, previous work focused on hippocampal astrocytes. Hence, we examined the impact of chronic immobilization stress (2 h/d, 10 d), on the number and structure of astrocytes in the rat hippocampus and amygdala. We observed a reduction in the number of glial fibrillary acidic protein (GFAP)-positive astrocytes in the basal amygdala (BA), 1 d after the end of 10 d of chronic stress. Detailed morphometric analysis of individual dye-filled astrocytes also revealed a decrease in the neuropil volume occupied by these astrocytes in the BA, alongside a reduction in the volume fraction of fine astrocytic protrusions rather than larger dendrite-like processes. By contrast, the same chronic stress had no effect on the number or morphology of astrocytes in hippocampal area CA3. We also confirmed previous reports that chronic stress triggers dendritic hypertrophy in dye-filled BA principal neurons that were located adjacent to astrocytes that had undergone atrophy. Thus, building on earlier evidence for contrasting patterns of stress-induced plasticity in neurons across brain areas, our findings offer new evidence that the same stress can also elicit divergent morphological effects in astrocytes in the hippocampus versus the amygdala
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