BDNF-TrkB signaling in oxytocin neurons contributes to maternal behavior.

Kristen R Maynard,Joo Heon Shin,Amolika Gupta,Keri Martinowich,Courtney Williams,Badoi N Phan,Andrew E Jaffe,Anandita Rajpurohit,Sumita Rajpurohit,John W Hobbs

doi:10.7554/elife.33676

Abstract

Brain-derived neurotrophic factor (Bdnf) transcription is controlled by several promoters, which drive expression of multiple transcripts encoding an identical protein. We previously reported that BDNF derived from promoters I and II is highly expressed in hypothalamus and is critical for regulating aggression in male mice. Here we report that BDNF loss from these promoters causes reduced sexual receptivity and impaired maternal care in female mice, which is concomitant with decreased oxytocin (Oxt) expression during development. We identify a novel link between BDNF signaling, oxytocin, and maternal behavior by demonstrating that ablation of TrkB selectively in OXT neurons partially recapitulates maternal care impairments observed in BDNF-deficient females. Using translating ribosome affinity purification and RNA-sequencing we define a molecular profile for OXT neurons and delineate how BDNF signaling impacts gene pathways critical for structural and functional plasticity. Our findings highlight BDNF as a modulator of sexually-dimorphic hypothalamic circuits that govern female-typical behaviors.

Highlights

Brain-derived neurotrophic factor (BDNF) is an activity-dependent neurotrophin that binds the receptor tropomyosin receptor kinase B (TrkB) to mediate many aspects of brain plasticity (Andero et al, 2014; Chao et al, 2006; Lu, 2003)
Given that BDNF is a robust modulator of gene expression and has been associated with remodeling of GABAA receptors in hypothalamic neuroendocrine cells (Choe et al, 2015; Hewitt and Bains, 2006), we investigated the role of BDNF in regulating gene transcription and plasticity in OXT neurons during female-typical social behaviors
BDNF derived from promoters I and II regulates maternal care and mating in females To assess whether Brain-derived neurotrophic factor (Bdnf)-e1 or -e2 -/- postpartum mothers show impairments in parenting behaviors, we first examined pup survival from parturition until postnatal day 3 (P3)

Summary

Introduction

Brain-derived neurotrophic factor (BDNF) is an activity-dependent neurotrophin that binds the receptor tropomyosin receptor kinase B (TrkB) to mediate many aspects of brain plasticity (Andero et al, 2014; Chao et al, 2006; Lu, 2003). While it is established that BDNF modulates social behavior in males (Chan et al, 2006; Ito et al, 2011; Lyons et al, 1999), no studies to-date have investigated the role of BDNF-TrkB signaling in influencing female-typical social behaviors, mating and maternal care. This is especially surprising given the wealth of literature

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