Traumatic Stress Produces Distinct Activations of GABAergic and Glutamatergic Neurons in Amygdala.

Qing Fang,Zeng-Bo Ding,Ya-Yun Chen,Lin Lu,Zhe Li,Jie Shi,Huan-Huan Zhang,Jian-Li Yang,Geng-Di Huang,Li-Bo Zhang

doi:10.3389/fnins.2018.00387

Abstract

Posttraumatic stress disorder (PTSD) is an anxiety disorder characterized by intrusive recollections of a severe traumatic event and hyperarousal following exposure to the event. Human and animal studies have shown that the change of amygdala activity after traumatic stress may contribute to occurrences of some symptoms or behaviors of the patients or animals with PTSD. However, it is still unknown how the neuronal activation of different sub-regions in amygdala changes during the development of PTSD. In the present study, we used single prolonged stress (SPS) procedure to obtain the animal model of PTSD, and found that 1 day after SPS, there were normal anxiety behavior and extinction of fear memory in rats which were accompanied by a reduced proportion of activated glutamatergic neurons and increased proportion of activated GABAergic neurons in basolateral amygdala (BLA). About 10 days after SPS, we observed enhanced anxiety and impaired extinction of fear memory with increased activated both glutamatergic and GABAergic neurons in BLA and increased activated GABAergic neurons in central amygdala (CeA). These results indicate that during early and late phase after traumatic stress, distinct patterns of activation of glutamatergic neurons and GABAergic neurons are displayed in amygdala, which may be implicated in the development of PTSD.

Highlights

Posttraumatic stress disorder (PTSD) is a complex, chronic mental disorder, and its lifetime prevalence is approximately 1.0–2.6% in the general population (APA, 2000, 2013b)
Open Field Test (OFT) and Elevated Plus Maze (EPM) were used to assess the SPSinduced anxiety-like behaviors, and Contextual Fear Conditioning (CFC) was applied to assess the single prolonged stress (SPS)-induced impairment of fear extinction retention
On day 10 after stress, total number of activated neurons and the proportion of activated cells in the GAD67+ type cells were significantly increased in central amygdala (CeA). These results indicate that SPS produces distinct pattern of neuronal activation in basolateral amygdala (BLA) and CeA on day 1 and day 10 after stress, which is consistent with previous study that the PTSD-associated behaviors accompanied with dysfunction of glutamatergic and GABAergic transmission in central nervous system (Knox et al, 2010)

Summary

Introduction

Posttraumatic stress disorder (PTSD) is a complex, chronic mental disorder, and its lifetime prevalence is approximately 1.0–2.6% in the general population (APA, 2000, 2013b). The vulnerable individuals are susceptible to the stress events of life-threatening illness or serious injuries such as traffic accidents, sexual assault, rape, natural disasters, or wars (Olaya et al, 2015; Benjet et al, 2016). This mental disorder contains three main symptom clusters: the reexperiencing and intrusive memories of the traumatic event (TE), avoidance behaviors, and emotional numbing, a sustained state of hypervigilance and startle response enhancement, which affect patients’ daily skills (APA, 2000, 2013a). There is still a subgroup of PTSD patients who have some persistent symptoms or maintain conditioned fear responses to TEs, being chronic

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Conclusion