BDNF-TrkB signaling in oxytocin neurons contributes to maternal behavior
- Lieber Institute for Brain Development, United States
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.
Data availability
All RNA-seq analysis code and source data are available on the GitHub repository: https://github.com/LieberInstitute/oxt_trap_seq/. Raw sequencing reads are available on SRA under accession code SRP157978.
-
BDNF-TrkB signaling in oxytocin neurons contributes to maternal behaviorRaw sequencing reads are available on SRA under accession code SRP157978.
-
Rapid molecular profiling of defined cell types using viral TRAPPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE89737).
Article and author information
Author details
Funding
National Institute of Mental Health (T32MH01533037)
- Kristen R Maynard
Lieber Institute for Brain Development
- Keri Martinowich
National Institute of Mental Health (RO1MH105592)
- Keri Martinowich
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental animal procedures were approved by the Sobran Biosciences Institutional Animal Care and Use Committee (IACUC) under protocol number LIE-004-2015.
Copyright
© 2018, Maynard et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,770
- views
-
- 439
- downloads
-
- 38
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Further reading
-
- Neuroscience
Adaptive behavior in complex environments critically relies on the ability to appropriately link specific choices or actions to their outcomes. However, the neural mechanisms that support the ability to credit only those past choices believed to have caused the observed outcomes remain unclear. Here, we leverage multivariate pattern analyses of functional magnetic resonance imaging (fMRI) data and an adaptive learning task to shed light on the underlying neural mechanisms of such specific credit assignment. We find that the lateral orbitofrontal cortex (lOFC) and hippocampus (HC) code for the causal choice identity when credit needs to be assigned for choices that are separated from outcomes by a long delay, even when this delayed transition is punctuated by interim decisions. Further, we show when interim decisions must be made, learning is additionally supported by lateral frontopolar cortex (lFPC). Our results indicate that lFPC holds previous causal choices in a ‘pending’ state until a relevant outcome is observed, and the fidelity of these representations predicts the fidelity of subsequent causal choice representations in lOFC and HC during credit assignment. Together, these results highlight the importance of the timely reinstatement of specific causes in lOFC and HC in learning choice-outcome relationships when delays and choices intervene, a critical component of real-world learning and decision making.
-
- Neuroscience
Animals navigate the auditory world by recognizing complex sounds, from the rustle of a predator to the call of a potential mate. This ability depends in part on the octopus cells of the auditory brainstem, which respond to multiple frequencies that change over time, as occurs in natural stimuli. Unlike the average neuron, which integrates inputs over time on the order of tens of milliseconds, octopus cells must detect momentary coincidence of excitatory inputs from the cochlea during an ongoing sound on both the millisecond and submillisecond time scale. Here, we show that octopus cells receive inhibitory inputs on their dendrites that enhance opportunities for coincidence detection in the cell body, thereby allowing for responses both to rapid onsets at the beginning of a sound and to frequency modulations during the sound. This mechanism is crucial for the fundamental process of integrating the synchronized frequencies of natural auditory signals over time.
