Acute Stress Suppresses Synaptic Inhibition and Increases Anxiety via Endocannabinoid Release in the Basolateral Amygdala

Shi, Dan; Itoga, Christy A.; Fisher, Marc O.; Solomonow, Jonathan; Roltsch, Emily; Gilpin, Nicholas W.; Tasker, Jeffrey G.

doi:10.1523/jneurosci.2279-15.2016

Cited by 95 publications

(74 citation statements)

References 44 publications

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“…Our data are somewhat at odds with a recent report by Di et al, suggesting that in rats 2-AG signaling in the amygdala contributes to anxiety-like behavior in the open-field, but not elevated-plus maze, after restraint stress exposure (54). These authors did find, however, that blockade of CB1 receptors in the amygdala under control conditions increased anxiety-like behavior in the open-field, which is consistent with our data.…”

Section: Discussioncontrasting

confidence: 99%

Functional Redundancy Between Canonical Endocannabinoid Signaling Systems in the Modulation of Anxiety

Bedse

Hartley

Neale

et al. 2017

Biological Psychiatry

102

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Background Increasing the available repertoire of effective treatments for mood and anxiety disorders represents a critical unmet need. Pharmacological augmentation of endogenous cannabinoid (eCB) signaling has been suggested to represent a novel approach to the treatment of anxiety disorders; however, the functional interactions between two canonical eCB pathways mediated via anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the regulation of anxiety are not well understood. Methods We utilized pharmacological augmentation and depletion combined with behavioral and electrophysiological approaches to probe the role of 2-AG signaling in the modulation of stress-induced anxiety, and the functional redundancy between AEA and 2-AG signaling in the modulation of anxiety-like behaviors in mice. Results Selective 2-AG augmentation reduced anxiety in the light-dark box assay, and prevented stress-induced increases in anxiety associated with limbic AEA deficiency. In contrast, acute 2-AG depletion increased anxiety-like behaviors, which was normalized by selective pharmacological augmentation of AEA signaling and via direct CB1 receptor stimulation with tetrahydrocannabinol (THC). Electrophysiological studies revealed 2-AG modulation of amygdala glutamatergic transmission as a key synaptic correlate of the anxiolytic effects of 2-AG augmentation. Conclusions Although AEA and 2-AG likely subserve distinct physiological roles, a pharmacological and functional redundancy between these canonical eCB signaling pathways exists in the modulation of anxiety-like behaviors. These data support development of eCB-based treatment approaches for mood and anxiety disorders and suggest a potentially wider therapeutic overlap between AEA and 2-AG augmentation approaches than previously appreciated.

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Section: Discussioncontrasting

confidence: 99%

Functional Redundancy Between Canonical Endocannabinoid Signaling Systems in the Modulation of Anxiety

Bedse

Hartley

Neale

et al. 2017

Biological Psychiatry

102

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“…Amygdala is one of the key mediators of the influence of acute stress on emotion and cognition [20–22]. The enhanced glutamatergic transmission has been known to essentially account for the recruitment of amygdala by acute stress [23, 24].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, acute stress also recruits the inhibitory network in BA. Such recruitment, however, is somewhat at odds with the amygdala disinhibition following acute stress [20]. We speculate it may reflect a compensative response of the local inhibitory network, which may help to prevent excessive disinhibition in amygdala upon the emergence of acute stress and thus to ensure the appropriate stress response.…”

Section: Discussionmentioning

confidence: 99%

Acute stress enhances the glutamatergic transmission onto basoamygdala neurons embedded in distinct microcircuits

Song

Zhang²,

Wang³

et al. 2017

Mol Brain

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Amygdala activation is known to be critical for the processing of stressful events in brain. Recent studies have shown that the projection neurons (PNs) in amygdala, although architecturally intermingled, are integrated into distinct microcircuits and thus play divergent roles in amygdala-related behaviors. It remains unknown how stress regulates the individual amygdala PNs embedded in distinct microcircuits. Here, by using retrograde tracing and electrophysiological recording in in vitro slices, we explored the modulation of acute immobilization stress (AIS) on the basoamygdala (BA) PNs projecting either to medial prefrontal cortex (mPFC) or elsewhere, which we designated as BA-mPFC and non-BA-mPFC PNs respectively. The results showed that in the control mice, both the excitatory and inhibitory postsynaptic currents (sEPSCs/sIPSCs) were comparable between these two subsets of BA PNs. The influences of AIS on sEPSCs and sIPSCs were overall similar between the two neuronal populations. It markedly increased the sEPSCs amplitude but left unaltered their frequency as well as the sIPSCs amplitude and frequency. Despite this, several differences emerged between the effects of AIS on the distribution of sEPSCs/sIPSCs frequency in these two groups of BA PNs. Similar changes were also observed in the sEPSCs/sIPSCs of the two PN populations from mice experiencing forced swimming stress. Their intrinsic excitability, on the other hand, was nearly unaltered following AIS. Our results thus suggest that acute stress recruit both BA-mPFC and non-BA-mPFC PNs mainly through enhancing the glutamatergic transmission they receive.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-016-0283-6) contains supplementary material, which is available to authorized users.

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“…Even a markedly shorter duration of the same physical stressor, a single 2‐hr exposure to immobilization, that fails to have any impact on spine density or dendritic arborization 1 day later, leads to a significant increase in BLA spine density 10 days later (Mitra, Jadhav, McEwen, Vyas, & Chattarji, ). This delayed spinogenesis 10 days after acute stress is paralleled by enhanced excitatory glutamatergic synaptic transmission (Yasmin, Saxena, McEwen, & Chattarji, ) in the BLA, as well as higher anxiety‐like behavior (Mitra et al, ; Di et al, ). Further, brain‐derived neurotrophic factor (BDNF) is up‐regulated in the BLA 1 day after acute stress and this increase persists even 10 days later (Lakshminarasimhan & Chattarji, ).…”

Section: Introductionmentioning

confidence: 99%

Hippocampal and amygdalar cell‐specific translation is similar soon after stress but diverge over time

et al. 2018

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Stress is known to cause contrasting patterns of morphological and physiological plasticity in the hippocampus and amygdala. An obligatory cellular process underlying such neural changes is de novo translation and alterations in protein expression. Yet the nature of the translational response to stress in neurons remains largely unexplored. Even less is known about how glia are affected. Using a click-chemistry-based method to label the de novo proteome in live brain slices, we monitored translation in neurons and astrocytes of the basolateral amygdala (BLA) and dorsal hippocampal area CA3 (dCA3) in rats at different time-points after a single 2-hr exposure to immobilization stress. We observed enhancements in neuronal translation in both brain regions 1 hour after stress. This initial increase persisted in the BLA up to 10 days afterwards. In contrast, dCA3 neuronal translation gradually decreased to below control levels 10 days later. Translation profiles of dCA3 astrocytes followed timelines similar to neurons, but in BLA astrocytes translation peaked 1 day later and remained elevated 10 days later. Together our results demonstrate that stress causes an immediate upregulation of protein synthesis in both amygdalar and hippocampal neurons and astrocytes. However, these two areas eventually exhibit opposite temporal profiles of protein expression well after the end of stress. These findings identify new metrics of stress-induced plasticity at the level of cell-type specific proteomic landscape that may provide important insights into the molecular basis of the divergent temporal effects of stress across brain regions and biological scales.

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Acute Stress Suppresses Synaptic Inhibition and Increases Anxiety via Endocannabinoid Release in the Basolateral Amygdala

Cited by 95 publications

References 44 publications

Functional Redundancy Between Canonical Endocannabinoid Signaling Systems in the Modulation of Anxiety

Functional Redundancy Between Canonical Endocannabinoid Signaling Systems in the Modulation of Anxiety

Acute stress enhances the glutamatergic transmission onto basoamygdala neurons embedded in distinct microcircuits

Hippocampal and amygdalar cell‐specific translation is similar soon after stress but diverge over time

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