Network and behavioral signatures of postpartum behavioral deficits improve with a neurosteroid-based treatment
- 1Tufts University School of Medicine
Abstract
Postpartum depression (PPD) impacts nearly 20% of mothers and a much larger percentage (up to 75%) suffer from postpartum blues. Despite this high incidence, we still have an incomplete understanding of the underlying neurobiology of PPD. Deficits in neurosteroid signaling has been implicated in the vulnerability to postpartum behavioral deficits and mice with reduced expression of {delta} subunit-containing GABAA receptors (GABAARs) (Gabrd -/- or Gabrd +/-), the predominant site of action for 5-reduced neurosteroids, exhibit behavioral deficits restricted to the postpartum period. Allopregnanolone and allopregnanolone analogs (SGE-516) can improve postpartum behavioral outcomes and their ability to modulate oscillations in the basolateral amygdala (BLA) involved in emotional processing has been proposed to contribute to their antidepressant effects. Here we demonstrate that the behavioral differences in postpartum wild type, Gabrd+/-, and SGE-516-treated Gabrd+/- dams is largely driven by theta oscillations in the BLA. Previous studies have linked theta oscillations in the BLA to altered behavioral responding in response to stress or threat. Interestingly, here we demonstrate that Gabrd+/- dams exhibit a failure to properly respond to their own pup calls, with reduced theta oscillations that correlates with deficits in maternal approach behavior both of which are restored with SGE-516 treatment. Further, unbiased MoSeq analysis identified altered behavioral syllable expression in Gabrd+/- dams in response to their pup calls compared to wild type dams that are restored with SGE-516 treatment. These findings demonstrate network and behavioral signatures of postpartum behavioral deficits and characterize the effects associated with neurosteroid-based treatment response.
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BibTeX
@misc{htet2026network,
title = {{Network and behavioral signatures of postpartum behavioral deficits improve with a neurosteroid-based treatment}},
author = {L. Htet and G. Weiss and K. E. Dorst and S. Gray and M. Lewis and J. Maguire},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.25.754460},
url = {https://www.biorxiv.org/content/10.64898/2026.09.25.754460v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Network and behavioral signatures of postpartum behavioral deficits improve with a neurosteroid-based treatment
AU - L. Htet
AU - G. Weiss
AU - K. E. Dorst
AU - S. Gray
AU - M. Lewis
AU - J. Maguire
PY - 2026
DA - 2026/09/25
PB - bioRxiv
DO - 10.64898/2026.09.25.754460
UR - https://www.biorxiv.org/content/10.64898/2026.09.25.754460v1
AB - Postpartum depression (PPD) impacts nearly 20% of mothers and a much larger percentage (up to 75%) suffer from postpartum blues. Despite this high incidence, we still have an incomplete understanding of the underlying neurobiology of PPD. Deficits in neurosteroid signaling has been implicated in the vulnerability to postpartum behavioral deficits and mice with reduced expression of {delta} subunit-containing GABAA receptors (GABAARs) (Gabrd -/- or Gabrd +/-), the predominant site of action for 5-reduced neurosteroids, exhibit behavioral deficits restricted to the postpartum period. Allopregnanolone and allopregnanolone analogs (SGE-516) can improve postpartum behavioral outcomes and their ability to modulate oscillations in the basolateral amygdala (BLA) involved in emotional processing has been proposed to contribute to their antidepressant effects. Here we demonstrate that the behavioral differences in postpartum wild type, Gabrd+/-, and SGE-516-treated Gabrd+/- dams is largely driven by theta oscillations in the BLA. Previous studies have linked theta oscillations in the BLA to altered behavioral responding in response to stress or threat. Interestingly, here we demonstrate that Gabrd+/- dams exhibit a failure to properly respond to their own pup calls, with reduced theta oscillations that correlates with deficits in maternal approach behavior both of which are restored with SGE-516 treatment. Further, unbiased MoSeq analysis identified altered behavioral syllable expression in Gabrd+/- dams in response to their pup calls compared to wild type dams that are restored with SGE-516 treatment. These findings demonstrate network and behavioral signatures of postpartum behavioral deficits and characterize the effects associated with neurosteroid-based treatment response.
ER -