Many severe mental disorders with considerable disease burden such Autism Spectrum Disorders, Schizophrenia, and Major Depressive Disorder are characterized by profound social impairments. At present, there is little understanding of the origin of these social deficits, and efficient diagnosis and therapeutic options are lacking. Advanced molecular and genetic techniques make the discovery of specific neural circuits involved in social behavior possible, facilitating the development of diagnostics and novel therapeutic approaches specific to disorders with social deficits. We have taken advantage of newly developed molecular, genetic and systems- levels tools to uncover how specific neural populations and circuits involved in parental care, a social behavior essential for the survival and well-being of the offspring are regulated according to the animal sex and physiological status. Male and female mice show either affiliative or agonistic behavior toward infants depending on prior social experience. In recent work, we uncovered distinct subpopulations of hypothalamic neurons that are involved in the positive and negative regulation of male and female parenting behavior. The identification of these cell types with high granularity provides us with unique entry point to further dissect how changes in the molecular, biophysical and activity dynamics of distinct neuronal populations regulates parental care. We propose here to exploit the precise cell type identification of neuronal populations involved in the control of opposing infant-mediated behaviors and use high resolution molecular (Aim 1), neurophysiological (Aim 2) and systems-level (Aim 3) approaches to dissect the entire circuitry associated with infant-directed social interactions and to explore how these circuits are modulated by the animal?s sex and physiological state.
Many severe mental disorders are characterized by impairments in social interactions, yet these diseases are poorly understood, and current treatments are lacking to treat them effectively. Advanced molecular and genetic technologies allow for the dissection of dedicated neural pathways involved in specific behaviors, providing novel targets for diagnosis and therapeutic development. This proposal aims to leverage cutting edge molecular, electrophysiological and imaging approaches to uncover the molecular, biophysical and systems-level regulation of neural circuits underlying affiliative and agonistic behavior of males and females toward infants.
| Kohl, Johannes; Dulac, Catherine (2018) Neural control of parental behaviors. Curr Opin Neurobiol 49:116-122 |
| Moffitt, Jeffrey R; Bambah-Mukku, Dhananjay; Eichhorn, Stephen W et al. (2018) Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region. Science 362: |
| Kohl, Johannes; Babayan, Benedicte M; Rubinstein, Nimrod D et al. (2018) Functional circuit architecture underlying parental behaviour. Nature 556:326-331 |
| Kohl, Johannes; Autry, Anita E; Dulac, Catherine (2017) The neurobiology of parenting: A neural circuit perspective. Bioessays 39:1-11 |
| Renier, Nicolas; Adams, Eliza L; Kirst, Christoph et al. (2016) Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes. Cell 165:1789-1802 |
| Moffitt, Jeffrey R; Hao, Junjie; Bambah-Mukku, Dhananjay et al. (2016) High-performance multiplexed fluorescence in situ hybridization in culture and tissue with matrix imprinting and clearing. Proc Natl Acad Sci U S A 113:14456-14461 |
