Which Brain Circuits Determine Maternal Behavior?

MedicalResearch.com Interview with:
“Mother and Child” by Mary Cassatt (American, Pittsburgh, Pennsylvania 1844–1926 Le Mesnil-Théribus, Oise) via The Metropolitan Museum of Art is licensed under CC0 1.0Yi-Ya Fang

NYU School of Medicine
Dayu Lin, PhD
Neuroscience Institute, New York University Langone School of Medicine,  Department of Psychiatry,
Center for Neural Science
New York, NY

Response: Maternal behaviors are essential for survival of offspring across mammalian species. In rodents, mothers show several characteristic pup caring behaviors including grooming pups, crouching over pups and approaching and retrieving pups. Decades of research has been trying to understand how the neural circuit is wired to generate these elaborate maternal behaviors. Medial preoptic area (MPOA), which is located at anterior part of hypothalamus, has been indicated to be important for maternal behaviors. Many studies consistently found deficits in maternal behaviors after damaging the MPOA. To dissect the maternal circuits in the brain, we looked into the properties of the Esr1+ cells.

In this study, we identify estrogen receptor α (Esr1) expressing cells in MPOA as key mediators of pup approach and retrieval. We focused on Esr1 (Esr1) expressing cells in the MPOA since estrogen has been shown to facilitate maternal behaviors, presumably through its action of estrogen sensing cells. We found that reversible inactivation of MPOA Esr1+ cells impairs maternal behaviors whereas optogenetic activation of MPOA Esr1+ cells induces immediate pup retrieval. Additionally, we found that MPOA Esr1+ cells are preferentially activated during maternal behaviors, and the cell responses changed across reproductive states. Tracing studies revealed that MPOA Esr1+ cells project strongly to ventral tegmental area (VTA), a region that has been indicated in motivation and reward. Specifically, MPOA Esr1+ cells provide strong inhibitory inputs preferentially to the GABAergic cells in the VTA, which in turn could disinhibit the dopaminergic cells.  VTA dopaminergic cells are highly activated during maternal behaviors.

Altogether, our study provides new insight into the neural circuit that generates maternal behaviors.

MedicalResearch.com: Can this pathway be potentially blocked by drugs (ie alcohol, cocaine, meth etc)?

Response: Possibly. Our study pinpoint the dopaminergic system as a key relay for generating maternal behaviors. Drugs that influence the dopaminergic signaling in the brain could also impact maternal behaviors.

MedicalResearch.com: What should readers take away from your report?

Response: First, MPOA Esr1+ cells are the key cells for generating maternal behaviors. Second and perhaps not surprisingly, mothers’ brains are tuned to be more responsive to pups. Third, the dopamine system is not only for reward but also for proper execution of specific pup caring behaviors.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Our results have suggested changes of MPOA cell responses across reproductive states. It would be really interesting to understand what would be the possible factors that cause such changes during motherhood. MPOA has received multiple inputs from other upstream brain regions, such as medial amygdala (MeA) and anteroventral periventricular nucleus (AVPV), and how MPOA integrates the inputs and finally orchestrates maternal behaviors is unknown. In addition, VTA has been known to play a critical role in motivation system. Whether the MPOA to VTA pathway is involved in maternal motivation remains incompletely understood. Addressing these questions could further lead to better understanding of the maternal circuit in the brain.


A Hypothalamic Midbrain Pathway Essential for Driving Maternal Behaviors

Fang, Yi-Ya et al.
Neuron , Volume 98 , Issue 1 , 192 – 207.e10 

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