Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, United States
Amolika Gupta
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, United States
Sumita Rajpurohit
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, United States
Courtney Williams
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, United States
Anandita Rajpurohit
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, United States
Joo Heon Shin
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, United States
Andrew E Jaffe
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, United States; Department of Mental Health, Johns Hopkins University, Baltimore, United States; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States; Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, United States
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, United States; Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
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.
