Repeated social stress leads to contrasting patterns of structural plasticity in the amygdala and hippocampus

Abstract

Previous studies have demonstrated that repeated immobilization and restraint stress cause contrasting patterns of dendritic reorganization as well as alterations in spine density in amygdalar and hippocampal neurons. Whether social and ethologically relevant stressors can induce similar patterns of morphological plasticity remains largely unexplored. Hence, we assessed the effects of repeated social defeat stress on neuronal morphology in basolateral amygdala (BLA), hippocampal CA1 and infralimbic medial prefrontal cortex (mPFC). Male Wistar rats experienced social defeat stress on 5 consecutive days during confrontation in the resident-intruder paradigm with larger and aggressive Wild-type Groningen rats. This resulted in clear social avoidance behavior one day after the last confrontation. To assess the morphological consequences of repeated social defeat, 2 weeks after the last defeat, animals were sacrificed and brains were stained using a Golgi-Cox procedure. Morphometric analyses revealed that, compared to controls, defeated Wistar rats showed apical dendritic decrease in spine density on CA1 but not BLA. Sholl analysis demonstrated a significant dendritic atrophy of CA1 basal dendrites in defeated animals. In contrast, basal dendrites of BLA pyramidal neurons exhibited enhanced dendritic arborization in defeated animals. Social stress failed to induce lasting structural changes in mPFC neurons. Our findings demonstrate for the first time that social defeat stress elicits divergent patterns of structural plasticity in the hippocampus versus amygdala, similar to what has previously been reported with repeated physical stressors. Therefore, brain region specific variations may be a universal feature of stress-induced plasticity that is shared by both physical and social stressors.

Rodent models of social stress and neuronal plasticity: Relevance to depressive-like disorders

“…Repeated social stress in rats induces enhanced dendritic arborization in the basal dendrites of BLA pyramidal neurons. This effect is accompanied by an increase in social avoidance behavior suggesting stress-induced increase in social anxiety in the rats [66]. This confirms the previously published effect using models of physical stressors such as restraint and immobilization [50,69].…”

“…Chronic social defeat stress in susceptible mice decreases dendritic spine density in the neurons of CA3 and dentate gyrus region of hippocampus [72]. Repeatedly defeated rats from a feral strain (wild-type Groningen rats) exhibited robust decrease in spine density in the CA1 pyramidal apical dendrites [66]. Another study showed a significant decrease in stubby spines, and an increase in long-thin spines within the CA1 stratum radiatum region when adolescent male mice were subjected to 10 days of defeat [73].…”

“…The pyramidal neurons of mainly the prelimbic region undergo reversible structural remodeling like hippocampus [55,56,101,102]. On the other hand, dendritic atrophy in adult rats was not seen with repeated social defeat stress [66]. Moreover, with chronic restraint stress, an increase in the length and dendritic branching of the IL and PL pyramidal neurons was observed in females while opposite effects were observed in the male rats [103][104][105].…”

“…Multiple factors may be causal in volumetric changes such as structural remodeling, neuro-and gliogenesis and apoptosis [29,63,64]. Social stress paradigms such as psychosocial stress in the resident-intruder paradigm and chronic stress of subordination in the visible burrow system in several animal models showed dendritic atrophy in CA1 and CA3 pyramidal neurons that persisted even after prolonged stress free recovery periods [39,41,65,66]. Somewhat surprisingly, dendritic atrophy in CA3 neurons was not only observed in animals exposed to chronic social stress but also observed in rats that were socially dominant in social colony structures like the visible burrow system [65] which may indicate that maintaining social dominance can be a source of chronic social stress.…”

Imaging suicidal thoughts and behaviors: a comprehensive review of 2 decades of neuroimaging studies

“…Due to their roles in processing of emotion, emotional memory and stress response [104][105][106][107], the mesial temporal amygdala, hippocampus, and entorhinal cortex (BA28, within the adjacent parahippocampal gyrus) are also thought to be involved in STBs. However, findings reported have been inconsistent.…”