Adult hippocampal neurogenesis is functionally important for stress-induced social avoidance.
The long-term response to chronic stress is variable, with some individuals developing maladaptive functioning, although other "resilient" individuals do not. Stress reduces neurogenesis in the dentate gyrus subgranular zone (SGZ), but it is unknown if stress-induced changes in neurogenesis contribute to individual vulnerability. Using a chronic social defeat stress model, we explored whether the susceptibility to stress-induced social avoidance was related to changes in SGZ proliferation and neurogenesis. Immediately after social defeat, stress-exposed mice (irrespective of whether they displayed social avoidance) had fewer proliferating SGZ cells labeled with the S-phase marker BrdU. The decrease was transient, because BrdU cell numbers were normalized 24 h later. The survival of BrdU cells labeled before defeat stress was also not altered. However, 4 weeks later, mice that displayed social avoidance had more surviving dentate gyrus neurons. Thus, dentate gyrus neurogenesis is increased after social defeat stress selectively in mice that display persistent social avoidance. Supporting a functional role for adult-generated dentate gyrus neurons, ablation of neurogenesis via cranial ray irradiation robustly inhibited social avoidance. These data show that the time window after cessation of stress is a critical period for the establishment of persistent cellular and behavioral responses to stress and that a compensatory enhancement in neurogenesis is related to the long-term individual differences in maladaptive responses to stress.
Lagace
Diane C
DC
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9070, USA.
Donovan
Michael H
MH
DeCarolis
Nathan A
NA
Farnbauch
Laure A
LA
Malhotra
Shveta
S
Berton
Olivier
O
Nestler
Eric J
EJ
Krishnan
Vaishnav
V
Eisch
Amelia J
AJ
D000818:Animals; D001362:Avoidance Learning; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D055495:Neurogenesis; D016196:S Phase; D015398:Signal Transduction; D013315:Stress, Psychological / Q000473:pathology*
D019208:Brain-Derived Neurotrophic Factor; D001973:Bromodeoxyuridine