Regional differences in acute corticosterone-induced dendritic remodeling in the rat brain and their behavioral consequences

Abstract

Background: Glucocorticoid released by stressful stimuli elicits various stress responses. Acute treatment with a single dose of corticosterone (CORT; predominant glucocorticoid of rats) alone has previously been shown to trigger anxiety behavior and robust dendritic hypertrophy of neurons in the basolateral amygdala (BLA). Neurons in the medial prefrontal cortex (mPFC) are also known to be highly sensitive to stress and regulate anxiety-like behaviors. Nevertheless, we know less about acute CORT-induced structural changes of other brain regions and their behavioral outcomes. In addition, the temporal profile of acute CORT effects remains to be examined. The current study investigates time course changes of dendritic architectures in the stress vulnerable brain areas, the BLA and mPFC, and their behavioral consequences after acute treatment with a single dose of CORT.

Results: Acute CORT treatment produced delayed onset of dendritic remodeling in the opposite direction in the BLA and mPFC with different time courses. Acute CORT induced dendritic hypertrophy of BLA spiny neurons, which was paralleled by heightened anxiety, both peaked 12 days after the treatment. Meanwhile, CORT-induced dendritic atrophy of mPFC pyramidal neurons peaked on day 6, concomitantly with impaired working memory. Both changed dendritic morphologies and altered behavioral outcomes were fully recovered.

Conclusion: Our results suggest that stress-induced heightened anxiety appears to be a functional consequence of dendritic remodeling of BLA neurons but not that of mPFC. Instead, stress-induced dendritic atrophy of mPFC neurons is relevant to working memory deficit. Therefore, structural changes in the BLA and the mPFC might be specifically associated with distinct behavioral symptoms observed in stress-related mental disorders. Remarkably, stress-induced dendritic remodeling in the BLA as well as mPFC is readily reversible. The related behavioral outcomes also follow the similar time course in a reversible manner. Therefore, further studies on the cellular mechanism for the plasticity of dendrites architecture might provide new insight into the etiological factors for stress-related mental illness such as posttraumatic stress disorder (PTSD).

Figure 1

Experimental schedule and time course change of body weight. (A) Experimental schedule to study temporal aspects of behavioral and neuronal morphological changes after acute CORT treatment. Vehicle or CORT was subcutaneously administered on day 1 and time-course changes of behavior and dendritic arborization were measured on days 3, 6, 12 and 20. (B) Time course changes of body weight upon acute treatment of vehicle or CORT. Significance of difference in body weight was analyzed by using a two-way repeated-measures ANOVA. Delayed significant difference by acute CORT treatment was revealed on day 20. *, P < 0.05 (post hoc Bonferroni test).

Figure 2

Temporal changes in dendritic arborization of BLA neurons following acute CORT treatment. Acute CORT treatment elicited an increase in dendritic arborization 12 days after the treatment. The increase in dendritic arborization was manifested as increases in total dendritic length (A) and total number of branch points (B), and segmental analysis revealed an increase in dendritic arborization along a wide range of dendritic segments (C). Representative camera lucida drawings of Golgi-impregnated BLA pyramidal neurons for vehicle- or CORT- treated groups with various delay periods after the treatment (D).*, P < 0.05; **, P < 0.01; ***, P < 0.001 (post hoc Bonferroni test).

Figure 3

Temporal change in anxiety-like behavior in the EPM following acute CORT treatment. The increased anxiety level 12 days after acute CORT treatment was evident by a decrease in open arm duration (A) and a decrease in total number of open arm entry (B). *, P < 0.05 (post hoc Bonferroni test). No difference in total moving distance between vehicle- and CORT-treated groups indicates that the higher anxiety-level was not accompanied by difference in locomotion activity (C).

Figure 4

Temporal changes in dendritic arborization of mPFC neurons following acute CORT treatment. Acute CORT treatment elicited a decrease in dendritic arborization 3 and 6 days after the treatment. The decrease in dendritic arborization was manifested by decreased total dendritic length (A) and total number of branch points (B), and segmental analysis revealed an increase in dendritic arborization in the segments between 120 μm and 160 μm from the cell body (C). Representative camera lucida drawings of Golgi-impregnated mPFC pyramidal neurons for vehicle- or CORT- treated groups with various delay periods after the treatment (D). Only apical dendrites were depicted for clarity. *, P < 0.05; ***, P < 0.001 (post hoc Bonferroni test).

Figure 5

Temporal change in performance of working memory following acute CORT treatment. Impaired working memrory occurred 6 days after acute CORT treatment as evident by a decrease in percent of spontaneous alternations. *, P < 0.05 (post hoc Bonferroni test).