Stress duration modulates the spatiotemporal patterns of spine formation in the basolateral amygdala

Abstract

It has long been hypothesized that morphological and numerical alterations in dendritic spines underlie long-term structural encoding of experiences. Here we investigate the efficacy of aversive experience in the form of acute immobilization stress (AIS) and chronic immobilization stress (CIS) in modulating spine density in the basolateral amygdala (BLA) of male rats. We find that CIS elicits a robust increase in spine density across primary and secondary branches of BLA spiny neurons. We observed this CIS-induced spinogenesis in the BLA 1 d after the termination of CIS. In contrast, AIS fails to affect spine density or dendritic arborization when measured 1 d later. Strikingly, the same AIS causes a gradual increase in spine density 10 d later but without any effect on dendritic arbors. Thus, by modulating the duration of immobilization stress, it is possible to induce the formation of new spines without remodeling dendrites. However, unlike CIS-induced spine formation, the gradual increase in spine density 10 d after a single exposure to AIS is localized on primary dendrites. Finally, this delayed induction of BLA spinogenesis is paralleled by a gradual development of anxiety-like behavior on the elevated plus-maze 10 d after AIS. These findings demonstrate that stressful experiences can lead to the formation of new dendritic spines in the BLA, which is believed to be a locus of storage for fear memories. Our results also suggest that stress may facilitate symptoms of chronic anxiety disorders like post-traumatic stress disorder by enhancing synaptic connectivity in the BLA.anxiety ͉ dendritic remodeling ͉ immobilization ͉ synapse ͉ rats T he search for cellular substrates underlying experience-related plasticity has focused on dendritic spines ever since Ramón y Cajal (1, 2) proposed that the storage of long-term memory involves strengthening of synaptic connections (or even a building of new connections) among central neurons. More recently, the focus has shifted toward understanding the physiological and molecular basis of synaptic plasticity mechanisms, such as long-term potentiation (LTP), and their relationship to spine plasticity and ultimately behavioral memory (3, 4). A majority of these studies have examined the hippocampus. Although the hippocampus is required for the acquisition and temporary storage of declarative memory, studies with human subjects and animal models suggest that more permanent morphological correlates of long-term memory storage are unlikely to reside in the hippocampus (5-7). In this context, the amygdala, for which the neural circuit underlying emotional memory formation is well characterized (8), provides a significant advantage. The basolateral amygdala (BLA) is believed to be a site of storage for memories of fearful or stressful experiences (9-12). Furthermore, recent studies indicate that the synthesis of new proteins in the BLA is involved in the long-term consolidation of emotional memories (13). Thus, the BLA presents an attractive locus to investigate structural encodi...

Effects of Repeated Stress on Age-Dependent GABAergic Regulation of the Lateral Nucleus of the Amygdala

“…The increased excitatory response to glutamate could be caused by increased neuronal membrane excitability (Rosenkranz et al, 2010;Hetzel and Rosenkranz, 2014), increased function of NMDA or AMPA receptors (Adamec et al, 2005;Caudal et al, 2010;Mozhui et al, 2010;Suvrathan et al, 2014), reduced glutamatergic drive of GABAergic networks (Masneuf et al, 2014), or upregulation of glutamatergic receptors (Lei and Tejani-Butt, 2010;Gan et al, 2014). Increased glutamatergic synaptic transmission could be caused by increased glutamatergic inputs, as observed here and in other studies (Mitra et al, 2005;Vyas et al, 2006;Padival et al, 2013Padival et al, , 2015Suvrathan et al, 2014;Tsai et al, 2014). In contrast, there was little evidence for increased glutamatergic drive after repeated stress in adolescent rats.…”

Personality traits in rats predict vulnerability and resilience to developing stress-induced depression-like behaviors, HPA axis hyper-reactivity and brain changes in pERK1/2 activity

“…More generally, these results are consistent with a growing body of data indicating that the amygdala is more vulnerable than the hippocampus to the effects of stress. This difference is reflected by a faster reactivity of the structural features of the amygdala to the effects of stress exposure; 10 days of immobilization stress was shown to be sufficient to induce dendritic hypertrophy and spine formation in the basolateral amygdala (Mitra et al, 2005). Additionally, the difference is reflected by a slower ability of the amygdala to recover from chronic stress; even after 21 days of stress-free recovery from a previous chronic immobilization stress, a persistent increase in dendritic arborization in the basolateral amygdala spiny neurons was observed, whereas hippocampal CA3 atrophy had completely recovered by this time point (Vyas et al, 2004).…”

Variation in Mouse Basolateral Amygdala Volume is Associated With Differences in Stress Reactivity and Fear Learning

“…A related issue is whether BLA variation is a consequence rather than cause of differences in stress reactivity. While we do not discount this possibility it seems unlikely given evidence that chronic stress increases rather than decreases spine density and dendritic arborization in rats and mice (Vyas et al, 2002;Mitra et al, 2005;Govindarajan et al, 2006). On the other hand, because stress causes dendritic shrinkage in rodent ventromedial prefrontal cortex (vmPFC) (Wellman, 2001;Izquierdo et al, 2006;Radley et al, 2006), it would be of interest to examine vmPFC and fear-related behaviors mediated by vmPFC such as fear extinction (Quirk and Mueller, 2007) in mice with different BLA volumes.…”