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A line attractor encoding a persistent internal state requires neuropeptide signaling

Affiliations
  • 1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA; Tianqiao and Chrissy Chen Institute for Neuroscience, California Institute of Technology, Pasadena, CA, USA.
  • 2Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA; Program in Computation and Neural Systems, California Institute of Technology, Pasadena, CA, USA; Tianqiao and Chrissy Chen Institute for Neuroscience, California Institute of Technology, Pasadena, CA, USA.
  • 3Department of Statistics, Stanford University, Stanford, CA 94305, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.

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August 27, 2024

Abstract

Internal states drive survival behaviors, but their neural implementation is poorly understood. Recently, we identified a line attractor in the ventromedial hypothalamus (VMH) that represents a state of aggressiveness. Line attractors can be implemented by recurrent connectivity or neuromodulatory signaling, but evidence for the latter is scant. Here, we demonstrate that neuropeptidergic signaling is necessary for line attractor dynamics in this system by using cell-type-specific CRISPR-Cas9-based gene editing combined with single-cell calcium imaging. Co-disruption of receptors for oxytocin and vasopressin in adult VMH Esr1 neurons that control aggression diminished attack, reduced persistent neural activity, and eliminated line attractor dynamics while only slightly reducing overall neural activity and sex- or behavior-specific tuning. These data identify a requisite role for neuropeptidergic signaling in implementing a behaviorally relevant line attractor in mammals. Our approach should facilitate mechanistic studies in neuroscience that bridge different levels of biological function and abstraction.

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