Chronic Stress Causes Amygdala Hyperexcitability in Rodents

Department of Cellular and Molecular Pharmacology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
Biological psychiatry (Impact Factor: 10.26). 04/2010; 67(12):1128-36. DOI: 10.1016/j.biopsych.2010.02.008
Source: PubMed


Chronic stress is a major health concern, often leading to depression, anxiety, or when severe enough, posttraumatic stress disorder. While many studies demonstrate that the amygdala is hyperresponsive in patients with these disorders, the cellular neurophysiological effects of chronic stress on the systems that underlie psychiatric disorders, such as the amygdala, are relatively unknown.
In this study, we examined the effects of chronic stress on the activity and excitability of amygdala neurons in vivo in rats. We used in vivo intracellular recordings from single neurons of the lateral amygdala (LAT) to measure neuronal properties and determine the cellular mechanism for the effects of chronic stress on LAT neurons.
We found a mechanism for the effects of chronic stress on amygdala activity, specifically that chronic stress increased excitability of LAT pyramidal neurons recorded in vivo. This hyperexcitability was caused by a reduction of a regulatory influence during action potential firing, facilitating LAT neuronal activity. The effects of stress on excitability were occluded by agents that block calcium-activated potassium channels and reversed by pharmacological enhancement of calcium-activated potassium channels.
These data demonstrate a specific channelopathy that occurs in the amygdala after chronic stress. This enhanced excitability of amygdala neurons after chronic stress may explain the observed hyperresponsiveness of the amygdala in patients with posttraumatic stress disorder and may facilitate the emergence of depression or anxiety in other patients.

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    • "Likewise, positive modulation of SK channels, and the subsequent enhancement of AHPs, reduces action potential frequency (Lujan et al., 2009; Hopf et al., 2010b). Importantly, disruption of SK channel activity and the ensuing dysregulation of neuronal output appear to play an important role in the neurobiological response to stressors such as fear conditioning (Santini et al., 2008; McKay et al., 2009; Motanis et al., 2014), restraint stress (Rosenkranz et al., 2010; Hetzel and Rosenkranz, 2014), and chronic exposure to ethanol (Hopf et al., 2010a, 2010b; Mulholland et al., 2011). Over the years, the neuromodulator adenosine and its receptor system have gained appreciation as key regulators of neuronal excitability (Dunwiddie and Masino, 2001). "
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    The International Journal of Neuropsychopharmacology 02/2015; 18(6). DOI:10.1093/ijnp/pyv017 · 4.01 Impact Factor
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    • "It was observed that GAD 65 expression in the medial amygdala (MeA) of males negatively correlated with spatial learning: increased errors were associated with less GAD 65 expression in the MeA. This brain region is intriguing because it is responsible for emotional regulation [63] and is impacted by stress [17] [65] [69] [78] [79]. It is fascinating that the distribution of the data shows the Str-Imm males clustered together and with low GAD 65 expression. "
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    • "It is worth noting that whereas CIS and CUS have been shown to exert distinct effects on the structural remodeling in the limbic systems [12], we find that they both impair the tonic inhibition in amygdala. We propose that it may serve as a common mechanism for the aberrant activation of amygdala in response to both paradigms of chronic stress [14,33,34]. "
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