Periodic Remodeling in a Neural Circuit Governs Timing of Female Sexual Behavior

Cell. 2019 Nov 27;179(6):1393-1408.e16. doi: 10.1016/j.cell.2019.10.025. Epub 2019 Nov 14.

Abstract

Behaviors are inextricably linked to internal state. We have identified a neural mechanism that links female sexual behavior with the estrus, the ovulatory phase of the estrous cycle. We find that progesterone-receptor (PR)-expressing neurons in the ventromedial hypothalamus (VMH) are active and required during this behavior. Activating these neurons, however, does not elicit sexual behavior in non-estrus females. We show that projections of PR+ VMH neurons to the anteroventral periventricular (AVPV) nucleus change across the 5-day mouse estrous cycle, with ∼3-fold more termini and functional connections during estrus. This cyclic increase in connectivity is found in adult females, but not males, and regulated by estrogen signaling in PR+ VMH neurons. We further show that these connections are essential for sexual behavior in receptive females. Thus, estrogen-regulated structural plasticity of behaviorally salient connections in the adult female brain links sexual behavior to the estrus phase of the estrous cycle.

Keywords: anteroventral periventricular nucleus; emotional behavior; estrogen, progesterone; estrous cycle; plasticity; sexual behavior; sexually dimorphic behavior; ventromedial hypothalamus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Estrogens / metabolism
  • Estrous Cycle / drug effects
  • Female
  • Gonadal Steroid Hormones / pharmacology
  • Hypothalamus, Anterior / physiology
  • Male
  • Mice, Inbred C57BL
  • Nerve Net / drug effects
  • Nerve Net / physiology*
  • Neuronal Plasticity / drug effects
  • Neurons / drug effects
  • Neurons / metabolism
  • Ovary / metabolism
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Receptors, Progesterone / metabolism
  • Sexual Behavior, Animal / drug effects
  • Sexual Behavior, Animal / physiology*
  • Signal Transduction / drug effects
  • Time Factors

Substances

  • Estrogens
  • Gonadal Steroid Hormones
  • Receptors, Progesterone