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Corticosteroid-induced neural remodeling predicts behavioral vulnerability and resilience.

Neurons in distinct brain regions remodel in response to postnatal stressor exposure, and structural plasticity may underlie stress-related modifications in behavioral outcomes. Given the persistence of stress-related diseases such as depression, a critical next step in identifying the contributions of neural structure to psychopathology will be to identify brain circuits and cell types that fail to recover from stressor exposure. We enumerated dendritic spines during and after chronic stress hormone exposure in hippocampal CA1, deep-layer prefrontal cortex, and the basal amygdala and also reconstructed dendritic arbors of CA1 pyramidal neurons. Corticosterone modified dendritic spine density in these regions, but with the exception of the orbitofrontal cortex, densities normalized with a recovery period. Dendritic retraction of hippocampal CA1 neurons and anhedonic-like insensitivity to a sucrose solution also persisted despite a recovery period. Using mice with reduced gene dosage of p190rhogap, a cytoskeletal regulatory protein localized to dendritic spines, we next isolated structural correlates of both behavioral vulnerability (spine elimination) and resilience (spine proliferation) to corticosterone within the orbital cortex. Our findings provide novel empirical support for the perspective that stress-related structural reorganization of certain neuron populations can persist despite a "recovery" period from stressor exposure and that these modifications may lay a structural foundation for stressor vulnerability-or resiliency-across the lifespan.

Pubmed ID: 23407965 RIS Download

Mesh terms: Animals | Behavior, Animal | CA1 Region, Hippocampal | Corticosterone | Dendritic Spines | GTPase-Activating Proteins | Gene Dosage | Hippocampus | Lysine | Male | Mice | Mice, Inbred C57BL | Neurons | Resilience, Psychological | Stress, Psychological | rho GTP-Binding Proteins

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Associated grants

  • Agency: NINDS NIH HHS, Id: NS39475
  • Agency: NIAAA NIH HHS, Id: AA017537
  • Agency: NIH HHS, Id: P51 OD011132
  • Agency: NIGMS NIH HHS, Id: R01 GM100411
  • Agency: NIH HHS, Id: P51 OD11132
  • Agency: NCRR NIH HHS, Id: P51 RR165
  • Agency: NINDS NIH HHS, Id: R01 NS039475
  • Agency: NIDCR NIH HHS, Id: UL1 DE019586
  • Agency: NIDA NIH HHS, Id: T32 DA015040
  • Agency: NIAAA NIH HHS, Id: RL1 AA017537
  • Agency: NINDS NIH HHS, Id: P30 NS055077
  • Agency: NIDCR NIH HHS, Id: UL1-DE19586

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