Title: | Social Behavioral Deficits with Loss of Neurofibromin Emerge from Peripheral Chemosensory Neuron Dysfunction |
Author(s): | Moscato EH; Dubowy C; Walker JA; Kayser MS; |
Address: | "Department of Psychiatry, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA. Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. Department of Psychiatry, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Neuroscience, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA; Chronobiology and Sleep Institute, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: kayser@pennmedicine.upenn.edu" |
DOI: | 10.1016/j.celrep.2020.107856 |
Abstract: | "Neurofibromatosis type 1 (NF1) is a neurodevelopmental disorder associated with social and communicative disabilities. The cellular and circuit mechanisms by which loss of neurofibromin 1 (Nf1) results in social deficits are unknown. Here, we identify social behavioral dysregulation with Nf1 loss in Drosophila. These deficits map to primary dysfunction of a group of peripheral sensory neurons. Nf1 regulation of Ras signaling in adult ppk23(+) chemosensory cells is required for normal social behaviors in flies. Loss of Nf1 attenuates ppk23(+) neuronal activity in response to pheromones, and circuit-specific manipulation of Nf1 expression or neuronal activity in ppk23(+) neurons rescues social deficits. This disrupted sensory processing gives rise to persistent changes in behavior beyond the social interaction, indicating a sustained effect of an acute sensory misperception. Together our data identify a specific circuit mechanism through which Nf1 regulates social behaviors and suggest social deficits in NF1 arise from propagation of sensory misinformation" |
Keywords: | "Aging/metabolism Animals Behavior, Animal Courtship Drosophila Proteins/*metabolism Drosophila melanogaster/*physiology Female Male Mutation/genetics Nerve Tissue Proteins/*metabolism Sensory Receptor Cells/*metabolism/*pathology Signal Transduction *Soci;Neuroscience;" |
Notes: | "MedlineMoscato, Emilia H Dubowy, Christine Walker, James A Kayser, Matthew S eng DP2 NS111996/NS/NINDS NIH HHS/ U54 HD086984/HD/NICHD NIH HHS/ R21 NS096402/NS/NINDS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2020/07/09 Cell Rep. 2020 Jul 7; 32(1):107856. doi: 10.1016/j.celrep.2020.107856" |