Archival ReportPerineuronal Nets, Inhibitory Interneurons, and Anxiety-Related Ventral Hippocampal Neuronal Oscillations Are Altered by Early Life Adversity
Section snippets
Maternal Separation With Early Weaning
Twenty litters of C57BL/6J mice from two breeding cohorts were exposed to one of two rearing conditions at postnatal day 2 (P2): 1) nonhandled controls; or 2) maternal separation for 4 hours daily from P2 to P5 and 8 hours daily from P6 to P16. Pups in the latter group were weaned at P17 while control litters were weaned at the typical age of P21 (11). At age P60 to P70, mice underwent behavior testing (see Supplemental Methods).
Behavior
Anxiety and activity testing were carried out as detailed in the
MSEW Results in Increased Anxiety-like Behavior in Males in the Elevated Plus Maze
We observed increased anxiety-like behavior in two cohorts of MSEW male mice compared with male controls. MSEW mice in cohort one showed increased anxiety in the elevated plus maze (EPM), with a significantly lower percentage of entries into the open arms (Figure 1B). MSEW mice in cohort one also spent significantly more time in the closed arms (Figure 1C). To verify the reliability of this manipulation, we repeated behavioral tests with a second cohort of mice. MSEW mice from cohort two also
Discussion
Our findings confirmed previous studies that adult male mice subjected to MSEW exhibit an increase in anxiety-like behavior and activity levels (11). We further showed that MSEW increased theta power in the vHIP when in a novel environment, but not in a familiar environment, as well as increased phase amplitude coupling between theta and gamma in both settings. The analysis of cellular subtypes within the vHIP revealed that MSEW resulted in reduced densities of PV+ and SST+ interneurons in the
Acknowledgments and Disclosures
This work was supported by a C.V. Starr Fellowship (to SM) and National Institute of Mental Health Grant No. R01MH117459-01 (to EG).
We thank Adam T. Brockett and Patrick K. Monari for their advice and help with surgeries and experiments and Brandy A. Briones and Elise C. Cope for their helpful comments on the manuscript.
The authors report no biomedical financial interests or potential conflicts of interest.
References (76)
- et al.
Gender differences in the effects of childhood maltreatment on adult depression and anxiety: A systematic review and meta-analysis
Child Abuse Negl
(2018) Developmental timing of trauma exposure relative to puberty and the nature of psychopathology among adolescent girls
J Am Acad Child Adolesc Psychiatry
(2016)- et al.
Environmental adversities and psychotic symptoms: The impact of timing of trauma, abuse, and neglect
Schizophr Res
(2019 Mar) - et al.
Childhood adversity and psychiatric disorder in young adulthood: An analysis of 107,704 Swedes
J Psychiatr Res
(2016) - et al.
Ventral hippocampal lesions affect anxiety but not spatial learning
Behav Brain Res
(2003) - et al.
The role of the ventral dentate gyrus in anxiety-based behaviors
Neurobiol Learn Mem
(2015) - et al.
BLA to vHPC inputs modulate anxiety-related behaviors
Neuron
(2013) - et al.
Direct ventral hippocampal-prefrontal input is required for anxiety-related neural activity and behavior
Neuron
(2016) - et al.
Anxiolytic action on the behavioural inhibition system implies multiple types of arousal contribute to anxiety
J Affect Disord
(2000) - et al.
Synchronized activity between the ventral hippocampus and the medial prefrontal cortex during anxiety
Neuron
(2010)