Medial Amygdala – Chronic Stress
A recent study in Molecular Psychiatry provides new evidence that chronic stress generates structural remodelling of the brain amygdala, and particularly the shrinkage of medial amygdala neurons in mice.
Chronic stress has been linked to cognitive impairment, but it is also known that stress modifies the neuronal architecture in several brain cognitive areas.
However, little is known about the effects of chronic stressful conditions, and the use of antidepressants regarding the neuronal remodelling in the amygdala. This brain structure is involved with stress reactivity, memory, emotional reactions and fear, and anxiety-related behavioral responses.
Chronic stress modifies structurally our brain cells architecture, as part of an adaptive strategy, but failed resilience has been linked to the onset and recurrence of major depression. Such structural plasticity and neuronal remodelling are well-known to occur in areas involved with memory and cognition, such as the hippocampal area and the prefrontal cortex.
However, only recently, the amygdala has been linked to this process, when neurons in the basolateral amygdala were shown to exhibit enhanced dendritic arborisation in response to chronic immobilization stress (CIS).
Now, in the Molecular Psychiatry study, T Lau and colleagues, from the Laboratory of Neuroendocrinology of the Rockefeller University, NY, USA, showed that chronically stressed mice exhibit structural modifications in neurons of the amygdala that can be partially prevented by treating the animals with the novel antidepressant candidate acetyl-L-carnitine (LAC).
Despite the well-known role of the hippocampus and basolateral amygdala in behavioral, autonomic and endocrine responses to epigenetic environmental influences, less is known about the role of the medial amygdala in these processes. The investigators have uncovered contrasting signs of structural plasticity within the three sub-regions of the amygdala.
The authors used the chronic restraint stress (CRS) paradigm, by restraining the animals for 21 consecutive days, and observed different effects of stress over different nuclei of the amygdala.
They found that in the basolateral amygdala (mainly involved with external information processing) stress was associated with an increase in dendritic length and number of intersections in pyramidal neurons (a sign of plasticity and adaptation).
In apparent contrast, the neuronal branches of the medial amygdala (mainly involved with the expression of emotions) appeared to shrink after 21 days of CRS. Of note, the CRS effects in the medial amygdala were specific to the stellate neurons that showed the dendritic shrinkage.
Lau and colleagues then treated the mice orally with LAC, known for its almost immediate anti-depressive effect. Additionally to the cognitive and social anti-depressive effect observed in the treated mice, oral LAC increased neuronal branching, where medial amygdala stellate neurons were more complex and longer. No differences were observed in other types of neurons in these brain nuclei.
The authors discuss that the stress-induced structural shrinkage in the medial amygdala, as reported in this study, may represent a homeostatic adaptation to the increased glutamatergic overflow from the adjacent hippocampus, which directly projects to the medial amygdala.
The authors also discuss that stellate neurons from the medial amygdala are important components involved with the neuronal, and subsequent behavioral responses to chronic stress.
They conclude that the medial amygdala is identified in this study as a novel target of structural and functional remodeling by stressors and the new antidepressant candidate acetyl-L-carnitine.
Source: Mol Psychiatry 2016 May 31 doi: 10.1038/mp.2016.68. [Epub ahead of print]
Read More: Molecular Psychiatry
A 2019 study found that chronic stress produces projection-specific functional adaptations in baso-lateral amygdala (BLA) projection neurons (PNs). Particularly, these authors demonstrate that BLA PNs show rapid recruitment and recovery following acute stress exposure. The exposure to chronic stress causes persistent activation and hyperexcitability in PNs that do not project to the dorsomedial prefrontal cortex-targeting PNs (BLA→dmPFC) —which the authors then went on to identify as ventral hippocampus (vHPC) projectors.
The authors link these projection-specific changes to a downregulation of calcium- activated potassium (SK2) channel and sub-type function and show that selectively preventing this adaptation is sufficient to prevent chronic stress-induced neuronal excitability and anxiety-like behavior.
Another 2019 study describes for the first time the acute and long-term effects of chronic social defeat stress (CSDS) on prefrontal cortex (PFC) and basolateral amygdala (BLA) spine densities and in BLA dendritic arborisation. Specifically, spine densities of the apical dendrites from the PFC pyramidal neurons were decreased by CSDS in the long-term. In addition, CSDS increased BLA stellate neurons spine density in the short-term and dendritic arborisation in the long-term.
Taken together these results suggest the existence of persistent neuronal adaptations in the PFC and BLA in socially defeated mice. Particularly, spine density retraction in the PFC and increased BLA dendritic arborisation could represent an adaptive structural change allowing rapid expression of synaptic markers in response to fearful experiences.
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