Resilience against predator stress and dendritic morphology of amygdala neurons

Abstract

Individual differences in coping response lie at the core of vulnerability to conditions like post-traumatic stress disorder (PTSD). Like humans, not all animals exposed to severe stress show lasting change in affect. Predator stress is a traumatic experience inducing long-lasting fear, but not in all rodents. Thus, individual variation may be a cross species factor driving responsiveness to stressful events. The present study investigated neurobiological bases of variation in coping with severe stress. The amygdala was studied because it modulates fear and its function is affected by stress. Moreover, stress-induced plasticity of the amygdala has been related to induction of anxiety, a comorbid symptom of psychiatric conditions like PTSD. We exposed rodents to predator stress and grouped them according to their adaptability based on a standard anxiety test (the elevated plus maze). Subsequently we investigated if well-adapted (less anxious) and mal-adapted (extremely anxious) stressed animals differed in the structure of dendritic trees of their output neurons of the right basolateral amygdala (BLA). Two weeks after exposure to stress, well-adapted animals showed low anxiety levels comparable to unstressed controls, whereas mal-adapted animals were highly anxious. In these same animals, Golgi analysis revealed that BLA neurons of well-adapted rats exhibited more densely packed and shorter dendrites than neurons of mal-adapted or unstressed control animals, which did not differ. These data suggest that dendritic hypotrophy in the BLA may be a resilience marker against lasting anxiogenic effects of predator stress.

Figure 1

Plotted across handled, and stressed mal- and well-adapted groups in Figures A - D are mean + SEM of behaviors measured in the EPM. Within a given behavioral plot, means marked with the same letter do not differ, means marked differently differ, and means marked with two letters fall between and do not differ from means marked with either letter.

Figure 2

Plotted across handled, and stressed mal- and well-adapted groups in Figures A - C are mean + SEM of measures of open arm exploration (ratio time/entry) and risk in the EPM after covarying closed arm entries from them. Within a given behavioral plot, means marked with the same letter do not differ, means marked differently differ. Unmarked means in C do not differ.

Figure 3

Plotted across handled, and stressed mal- and well-adapted groups in Figures A - D are mean + SEM of dendritic morphological measures taken from BLA neurons (n = 30 neurons for well-adapted [10 cells from each of 3 rats], n = 25 for handled [6 cells from each of 3 rats and 7 cells from the fourth] and n = 39 [10 cells from each of 3 rats and 9 cells from the fourth] for mal-adapted groups of animals). Within a given plot, means marked with the same letter do not differ, means marked differently differ.

Figure 4

Qualitative representation of neurons from each group of animals. A. Schematic diagram of neuronal tracing from handled (left), well-adapted (middle) and mal-adapted (right) animals. Scale bar = 100 mm. B. A typical BLA field stained with Golgi, showing a stellate neuron at 500×.

Figure 5

Segmental analysis showing packing density (length per branch). A. Well-adapted animals show highest packing density compared to other two groups at a radial distance 75-125 mm from cell soma. B. Sholl's analysis (with a typical tracing of a golgi-stained neuron) used for determination of segmental branch-packing in all groups; each concentric circle with 25 mm radial distance away from inner one.

Figure 6

Scatter plots illustrating the variation of EPM ratio time with total dendritic length - A. scatter plot of predator stressed rats (well- and mal- adapted) only; B. scatter plot including all groups (handled and well- and mal- adapted).