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 propose to take advantage of newly developed molecular and genetic tools to uncover and characterize the specific neural populations and circuits involved in parental care, a social behavior essential for the survival and well-being of the offspring. Male and female mice show either affiliative or agonistic behavior toward infants depending on prior social experience. In recently published work, we uncovered a specific subpopulation of hypothalamic neurons that are essential for the control of male and female parenting behavior. This finding provides us with a unique entry point to genetically dissect behavior circuits underlying parental care and their modulation by intrinsic and environmental factors. Using a combination of genetic and functional tools, we aim to characterize the circuit involved in parental behavior (Aim I) and uncover neuronal subpopulations driving agonistic behavior toward pups (Aim II). We will determine the functional role of these genetically defined neural populations and associated projections in parenting or agonistic behavior toward pups using cutting-edge molecular techniques by tracing inputs and outputs to genetically defined neuronal populations and manipulating their activity.
In Aim III, we will perform an unbiased gene expression analysis to discover factors influencing the differential activity of the neurons and circuits associated with affiliative or agonistic behavior in males and females, and in different physiological circumstances.
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 and genetics approaches to uncover the neural circuits underlying affiliate and agonistic behavior of males and females toward the young, and to identify physiological and hormonal factors that modulate their function.
| 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 |
