A Hypothalamic Midbrain Pathway Essential for Driving Maternal Behaviors

Neuron. 2018 Apr 4;98(1):192-207.e10. doi: 10.1016/j.neuron.2018.02.019.


Maternal behaviors are essential for the survival of the young. Previous studies implicated the medial preoptic area (MPOA) as an important region for maternal behaviors, but details of the maternal circuit remain incompletely understood. Here we identify estrogen receptor alpha (Esr1)-expressing cells in the MPOA as key mediators of pup approach and retrieval. Reversible inactivation of MPOAEsr1+ cells impairs those behaviors, whereas optogenetic activation induces immediate pup retrieval. In vivo recordings demonstrate preferential activation of MPOAEsr1+ cells during maternal behaviors and changes in MPOA cell responses across reproductive states. Furthermore, channelrhodopsin-assisted circuit mapping reveals a strong inhibitory projection from MPOAEsr1+ cells to ventral tegmental area (VTA) non-dopaminergic cells. Pathway-specific manipulations reveal that this projection is essential for driving pup approach and retrieval and that VTA dopaminergic cells are reliably activated during those behaviors. Altogether, this study provides new insight into the neural circuit that generates maternal behaviors.

Keywords: dopamine; electrophysiology; estrogen receptor alpha; hypothalamus; maternal behaviors; medial preoptic area; neural circuit; optogenetics; pup retrieval; ventral tegmental area.

Publication types

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

MeSH terms

  • Animals
  • Estrogen Receptor alpha / biosynthesis
  • Female
  • Hypothalamus / chemistry
  • Hypothalamus / metabolism*
  • Maternal Behavior / physiology*
  • Maternal Behavior / psychology
  • Mesencephalon / chemistry
  • Mesencephalon / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Pathways / chemistry
  • Neural Pathways / metabolism
  • Organ Culture Techniques
  • Preoptic Area / chemistry
  • Preoptic Area / metabolism*
  • Ventral Tegmental Area / chemistry
  • Ventral Tegmental Area / metabolism*


  • Estrogen Receptor alpha