Abstract
Medial prefrontal cortex (mPFC), amygdala, and striatum neurocircuitry has been shown to play an important role in post-traumatic stress disorder (PTSD) pathology in humans. Clinical studies show hypoactivity in the mPFC and hyperactivity in the amygdala and striatum of PTSD patients, which has been associated with decreased mPFC glutamate levels. The ability to refine neurobiological characteristics of PTSD in an animal model is critical in furthering our mechanistic understanding of the disease. To this end, we exposed male rats to single-prolonged stress (SPS), a validated model of PTSD, and hypothesized that traumatic stress would differentially activate mPFC subregions [prelimbic (PL) and infralimbic (IL) cortices] and increase striatal and amygdalar activity, which would be associated with decreased mPFC glutamate levels. in vivo, neural activity in the subregions of the mPFC, amygdala, and striatum was measured using manganese-enhanced magnetic resonance imaging (MEMRI), and glutamate and N-acetylaspartate (NAA) levels in the mPFC and the dorsal striatum (dSTR) were measured using proton magnetic resonance spectroscopy (1H-MRS) longitudinally, in rats exposed to SPS or control conditions. As hypothesized, SPS decreased MEMRI-based neural activity in the IL, but not PL, cortex concomitantly increasing activity within the basolateral amygdala (BLA) and dorsomedial striatum (dmSTR). 1H-MRS studies in a separate cohort revealed SPS decreased glutamate levels in the mPFC and increased NAA levels in the dSTR. These results confirm previous findings that suggest SPS causes mPFC hypoactivation as well as identifies concurrent hyperactivation in dmSTR and BLA, effects which parallel the clinical neuropathology of PTSD.
Highlights
Dysfunction of ‘‘top-down’’ prefrontal cortex (PFC) control in post-traumatic stress disorder (PTSD) likely contributes to amygdala hyperactivity, which is thought to mediate disease characteristics, such as the inability to inhibit fear-related behaviors related to traumatic events (Shin and Liberzon, 2010)
The second goal was to determine if single-prolonged stress (SPS) changed longitudinal neural activity in vivo in subregions of the medial PFC (mPFC), amygdala, and STR using manganese-enhanced magnetic resonance imaging (MEMRI)
The a priori hypothesis of the current study was that SPS-exposed rats would show decreased Glu levels in the mPFC with increased neural activity in the PL, decreased neural activity in the IL, and increased neural activity in the basolateral amygdala (BLA) and dorsomedial STR (dmSTR)
Summary
Dysfunction of ‘‘top-down’’ prefrontal cortex (PFC) control in post-traumatic stress disorder (PTSD) likely contributes to amygdala hyperactivity, which is thought to mediate disease characteristics, such as the inability to inhibit fear-related behaviors related to traumatic events (Shin and Liberzon, 2010). Using proton magnetic resonance spectroscopy (1H-MRS), we and others have shown that glutamate (Glu) levels are decreased in the medial PFC (mPFC) of rodents exposed to the single-prolonged stress (SPS) model of PTSD (Knox et al, 2010; Perrine et al, 2016; Lim et al, 2017), consistent with human 1H-MRS studies in the ACC (Yang et al, 2015) Considering these parallels (Pitman et al, 2012), the present study aimed to confirm and extend our previous 1H-MRS findings by using manganese-enhanced magnetic resonance imaging (MEMRI) to quantify calciumdependent neural activity in mPFC and amygdala, longitudinally, before and after SPS
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