Serotonergic transcriptional programming determines maternal behavior and offspring survival

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Central serotonergic signaling influences many physiological processes, but a requirement for reproductive success has not been demonstrated. Using mouse dams with a specific disruption in serotonin neuron development, we found that serotonergic function is required for the nurturing and survival of offspring. Full rescue of survival depended on the mother's expression level of the upstream serotonergic transcriptional cascade. Thus, intrinsic transcriptional programming of maternal serotonergic activity determines the quality of nurturing and whether or not the organism survives.

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Figure 1: Pet-1 is required for reproductive success.
Figure 2: Full rescue of 5HT neuron phenotype, nurturing and offspring survival depends on maternal FEV expression level.


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We thank S. Herlitze for presubmission review of the manuscript. We thank R. Murphy for help with in situ hybridization, K. Lobur for assistance with behavioral testing, C. Wylie for help gathering confocal images, G. Casadesus and M. Ionno of the Case Western Reserve University Rodent Behavior Core, and the Case Transgenic and Targeting Core for BAC transgenic production. This work was supported by grants from the US National Institute of Mental Health (National Service Research Award pre-doctoral fellowship MH073296 to J.K.L.-H., RO1 MH062723 and P50 MH078028 to E.S.D., and MH 0754047 to S.G.B.).

Author information

This study was designed, interpreted and written by J.K.L.-H. and E.S.D. J.K.L.-H. carried out all of the experiments except for the electrophysiology. D.F. advised and performed statistical analyses on maternal care data. L.K.C. and S.G.B. carried out and analyzed the electrophysiological data.

Correspondence to Evan S Deneris.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–10, Supplementary Tables 1–4 and Supplementary Methods (PDF 6560 kb)

Supplementary Video 1

Pet-1−/− female during pup retrieval assay. (MOV 7836 kb)

Supplementary Video 2

Pet-1+/− female during pup retrieval assay. (MOV 4793 kb)

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Lerch-Haner, J., Frierson, D., Crawford, L. et al. Serotonergic transcriptional programming determines maternal behavior and offspring survival. Nat Neurosci 11, 1001–1003 (2008) doi:10.1038/nn.2176

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