Increases in dendritic spine density in BLA without metabolic changes in a rodent model of PTSD

Abstract

Imaging studies have shown abnormal amygdala function in patients with posttraumatic stress disorder (PTSD). In addition, alterations in synaptic plasticity have been associated with psychiatric disorders and previous reports have indicated alterations in the amygdala morphology, especially in basolateral (BLA) neurons, are associated with stress-related disorders. Since, some individuals exposed to a traumatic event develop PTSD, the goals of this study were to evaluate the early effects of PTSD on amygdala glucose metabolism and analyze the possible BLA dendritic spine plasticity in animals with different levels of behavioral response. We employed the inescapable footshock protocol as an experimental model of PTSD and the animals were classified according to the duration of their freezing behavior into distinct groups: "extreme behavioral response" (EBR) and "minimal behavioral response". We evaluated the amygdala glucose metabolism at baseline (before the stress protocol) and immediately after the situational reminder using the microPET and the radiopharmaceutical 18 F-FDG. The BLA dendritic spines were analyzed according to their number, density, shape and morphometric parameters. Our results show the EBR animals exhibited longer freezing behavior and increased proximal dendritic spines density in the BLA neurons. Neither the amygdaloid glucose metabolism, the types of dendritic spines nor their morphometric parameters showed statistically significant differences. The extreme behavior response induced by this PTSD protocol produces an early increase in BLA spine density, which is unassociated with either additional changes in the shape of spines or metabolic changes in the whole amygdala of Wistar rats.

Rodent models of stress and dendritic plasticity – Implications for psychopathology

“…Indeed, experiments factoring in individual differences suggest that such differences do exist. For example, rats that responded to inescapable foot shocks with high levels of freezing showed the aforementioned BLA hypertrophy, while low-freezing rats did not ( Neves et al, 2019 ). Rats either selected for or selective bred for high anxiety-like behavior have shorter PFC dendrites and fewer spines on HPC CA1 neurons than their low-anxiety counterparts even in the absence of experimental stress ( Miller et al, 2012 ; Widman et al, 2019 ).…”

Nutraceutical Interventions for Post-Traumatic Stress Disorder in Animal Models: A Focus on the Hypothalamic–Pituitary–Adrenal Axis

“…Roozendaal et al found that the growth of the dendritic spines affects abnormalities in the amygdala structure and function in severe stress-induced chronic anxiety [ 51 ]. Moreover, Neves et al demonstrated a footshock-induced increase in the proximal dendritic spine density of BLA neurons in a rat PTSD model [ 52 ]. Furthermore, animal studies also demonstrated that delayed spinogenesis and synaptic transmission in the BLA increased anxiety-related behavior after PTSD [ 53 ].…”

Disruption of amygdalaTsc2in adolescence leads to changed prelimbic cellular activity and generalized fear responses at adulthood in rats

“…In FRD, an imbalanced functionality of the fear circuitry, in particular between the amygdala and the medial prefrontal cortex (mPFC), has been highlighted. Human and laboratory-rodent studies show that adults suffering from PTSD, anxiety, or phobias display a disruption of amygdala's activity (Pavliša et al 2006;Bremner et al 2007;Shin and Handwerger 2009;Morey et al 2012;Neves et al 2019) associated with a dysfunctional mPFC (Shin and Handwerger 2009;Whitaker et al 2014). The fear network has the particularity to undergo an asynchronous development, especially between the early maturing amygdala, a major hub underlying associative fear learning (Gründemann and Lüthi 2015), and the late maturing medial prefrontal cortex (mPFC), which modulates fear expression and its maintenance in memory (Ledoux 1996;LeDoux 2000;Sierra-Mercado et al 2011).…”