Amygdala hyper-connectivity in a mouse model of unpredictable early life stress.
Transl Psychiatry. 2018-02-21; 8(1):
DOI: 10.1038/s41398-018-0092-z
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1. Transl Psychiatry. 2018 Feb 21;8(1):49. doi: 10.1038/s41398-018-0092-z.
Amygdala hyper-connectivity in a mouse model of unpredictable early life stress.
Johnson FK(1), Delpech JC(1)(2), Thompson GJ(3)(4), Wei L(1), Hao J(1), Herman
P(3), Hyder F(3)(5), Kaffman A(6).
Author information:
(1)Department of Psychiatry, Yale University School of Medicine, 300 George
Street, Suite 901, New Haven, CT, 06511, USA.
(2)Department of Newborn Medicine, Boston Children’s Hospital, Harvard medical
school, Boston, MA, 02115, USA.
(3)Department of Radiology & Biomedical Imaging and Magnetic Resonance Research
Center, Yale University, New Haven, CT, 06520, USA.
(4)iHuman Institute, ShanghaiTech University, 393 Middle Huaxia Road, Ren
Building, Room B204, Zhangjiang, Pudong, Shanghai, 201210, China.
(5)Department of Biomedical Engineering, Yale University, New Haven, CT, 06519,
USA.
(6)Department of Psychiatry, Yale University School of Medicine, 300 George
Street, Suite 901, New Haven, CT, 06511, USA. .
Childhood maltreatment is associated with a wide range of psychopathologies
including anxiety that emerge in childhood and in many cases persist in
adulthood. Increased amygdala activation in response to threat and abnormal
amygdala connectivity with frontolimbic brain regions, such as the hippocampus
and the prefrontal cortex, are some of the most consistent findings seen in
individuals exposed to childhood maltreatment. The underlying mechanisms
responsible for these changes are difficult to study in humans but can be
elucidated using animal models of early-life stress. Such studies are especially
powerful in the mouse where precise control of the genetic background and the
stress paradigm can be coupled with resting-state fMRI (rsfMRI) to map abnormal
connectivity in circuits that regulate anxiety. To address this issue we first
compared the effects of two models of early-life stress, limited bedding (LB) and
unpredictable postnatal stress (UPS), on anxiety-like behavior in juvenile and
adult mice. We found that UPS, but not LB, causes a robust increase in anxiety in
juvenile and adult male mice. Next, we used rsfMRI to compare frontolimbic
connectivity in control and UPS adult male mice. We found increased
amygdala-prefrontal cortex and amygdala-hippocampus connectivity in UPS. The
strength of the amygdala-hippocampal and amygdala-prefrontal cortex connectivity
was highly correlated with anxiety-like behavior in the open-field test and
elevated plus maze. These findings are the first to link hyperconnectivity in
frontolimbic circuits and increased anxiety in a mouse model of early-life
stress, allowing for more mechanistic understanding of parallel findings in
humans.
DOI: 10.1038/s41398-018-0092-z
PMCID: PMC5820270
PMID: 29463821 [Indexed for MEDLINE]