Care circuits | Science

A possible parental circuit emerges

I started my project by mapping the connections that MPOA^Girl neurons form with the rest of the brain. An impressive range of viruses has been developed for this purpose in recent years. Some have the ability to jump back into neural circuits, thus visualizing the direct inputs of a neuron. Others label the thin axonal arborizations and synaptic terminals of infected neurons. These tracing experiments revealed astounding complexity: the MPOAGal neurons receive inputs from about 20 brain areas and send a similar number of projections (8). However, on closer inspection, a simple organizational principle emerged: MPOA^Girl neurons are organized into distinct pools, or subpopulations, each projecting into a different brain zone. Curiously, each group has access to incoming information from the 20 areas of the brain (see figure).

Discrete neural clusters are active during specific parenting behaviors

We then asked which neural basins were crucial for parental behavior. In fact, most areas targeted by MPOA^Girl neurons play a role in parenting (2–4). We therefore sought to determine the most strongly activated pools during pup interactions. Three candidate pools were identified for further investigation: those projecting to peri-aqueducal gray (PAG), ventral tegmental region (VTA) and medial amygdala (MeA) (8).

Are these different pools active during specific aspects of parenting? Using fiber photometry, an imaging approach to record the activity of the population from genetically specified neurons in behavioral animals (9), we found the entire MPOA^Girl population to be activated in all the components of parenthood. Surprisingly, however, individual groups have been set for separate parenting episodes (8), suggesting that they might well represent functionally distinct modules. We tested this hypothesis by optogenetically manipulating each of the three pools of candidates.

Manipulation of specific clusters induces discrete parenting behaviors

First, we turned to the PAG. Sexually inexperienced male mice usually attack puppies and become parents only in the weeks following mating (ten). Striking thing, activation of the MPOA projection PAG^Girl neurons suppressed puppy-led aggression in such males and increased grooming of puppies in both sexes, suggesting that this pool controls an important driving force of parenting. On the other hand, the activation of the neuronal pool projecting the VTA did not directly affect the interactions between small ones. VTA plays a well-established role in the treatment of motivation and rewards (11, 12).

Because an increased motivation to interact with infants is a characteristic of parental animals (13), we inserted a climbing barrier between the tested animal and the puppies. In this simple test, the activation of the VTA projection pool significantly increased the frequency with which animals passed through the nest box, suggesting that this branch of the circuit controlled the motivation to interact with infants.

Finally, activate these MPOAs^Girl the neurons projecting into the MeA did not affect the interactions between the pups, nor the motivation to interact with the pups. However, we unexpectedly discovered that this manipulation suppressed interactions with adult mice, both male and female. This pool could therefore indirectly promote parenting by suppressing nonparental social behaviors.

Conclusions and next steps

Our work suggests a circuit pattern in which MPOA defined by projection^Girl Neural pools control each of the specific aspects of parenting. This provides a new model that allows a small population of genetically defined neurons to orchestrate complex behavior. But this also raises several intriguing questions. Do these pools interact with each other? If so, how is their activity coordinated? If not, can the variations from moment to moment of the sensory input determine which element of the circuit is active? And which basins control other motor aspects of parenting, such as small recovery or building a nest?

We and others have made notable progress in discovering how parenting and other social behaviors are wired into the brain (8, 14, 15). This knowledge is essential from both a basic and a clinical point of view. In humans, parental care is affected by stress and mental illnesses such as depression and postpartum anxiety, which together affect nearly 20% of mothers in the United States (16). Addressing how physiological states and environmental factors interact with these circuits could therefore open new avenues for the treatment of common mental illnesses.