Social Behavioral Deficits with Loss of Neurofibromin Emerge from Peripheral Chemosensory Neuron Dysfunction

Cell Rep. 2020 Jul 7;32(1):107856. doi: 10.1016/j.celrep.2020.107856.


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: Drosophila melanogaster; Ras; autism; gustatory sensory neurons; neural circuits; neurofibromatosis type 1; neurofibromin 1; ppk23; sensory processing; social behavior.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aging / metabolism
  • Animals
  • Behavior, Animal
  • Courtship
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / physiology*
  • Female
  • Male
  • Mutation / genetics
  • Nerve Tissue Proteins / metabolism*
  • Sensory Receptor Cells / metabolism*
  • Sensory Receptor Cells / pathology*
  • Signal Transduction
  • Social Behavior*
  • ras GTPase-Activating Proteins / metabolism*
  • ras Proteins / metabolism


  • Drosophila Proteins
  • NF1 protein, Drosophila
  • Nerve Tissue Proteins
  • ras GTPase-Activating Proteins
  • ras Proteins