1. What is affiliative social behavior ?

Among social behaviors, those that bring members of a society together and build coexistence.

<ex.>

● Parenting of parents

● Attachment of the children to the parents

● Family relationships

● Gathering behavior

● Cooperative behavior such as group hunting and division of labor

■ Sexual behavior 

■ Confrontational and aggressive behavior (e.g., territorial disputes)

We are particularly interested and studying in the neural mechanisms of the parent-child relationship, which is conserved throughout the mammalian species. The ultimate goal of our research is to understand and support the human parent-child relationship.

2. Mammalian parent-child relationship

Mammalian children are born undeveloped and must be lactated, protected, and otherwise cared for by their parents in order to thrive. Therefore, children have the necessary neural pathways for “attachment behavior” to adore their parents and parents have the necessary neural pathways for “parenting behavior” to raise their children. (To be good at this requires experience and learning.)

<Four elements of the parent-child relationship>

<Parent-child behaviors and reactions necessary for breastfeeding>

Lactation, which appears to be a natural process, is actually a complex phenomenon that is accomplished through repeated interactions between parent and child, to which the other responds.

<Parent-child relationship in mice>

Since the parent-child relationship is essential for the survival of all mammals, the basic brain mechanisms of the parent-child relationship should also be evolutionarily conserved. We are investigating the neural mechanisms of nurturance and attachment primarily in mice, animals in which both parents often care for their offspring.

<Retrieving assay>

　Time required to collect 3 pups
　mother　within 3 minutes
　father　about 5 minutes
　virgin mother　15-60 minutes
　virgin father　Often not collected

Retrieving (carrying pups and collecting them in the nest) is a parenting behavior that can be performed by mice other than the mother, and is useful for measuring parenting motivation and skill.

3. Methods of Neuroscience Research on the Parent-Child Relationship

How do we investigate the brain mechanisms of the parent-child relationship?

1. Search for brain regions that are activated during parenting by cFos expression mapping, etc.

2. Investigate whether inhibition of that brain region specifically inhibits parenting

3. Examine the input/output and neuron types in that brain region.

4. Find out how behavior is changed by manipulating the activity of each neuron type

5. Search for genes specifically expressed in the involved neurons and manipulate gene-specific expression to see how the behavior is changed.
   
   

4. Parenting Center: medical preoptic area of hypothalamus (MPOA)

MPOA : the medical preoptic area of hypothalamus

Since MPOA is activated during parenting and disruption of MPOA specifically inhibits parenting, it is believed to play a very important function in nurturing behavior.

(Numan, 1974; Terkel et al, 1979; Kalinichev et al., 2000), (Cala-mandrei and Keverne, 1994; Numan and Numan, 1994; Li et al., 1999)

Of the MPOA, the central part, the cMPOA, is the most important in nurturing behavior. cMPOA destruction does not inhibit mating or childbearing, but does not allow for parenting specifically.

On the other hand, it was the non-oxitocin neurons of the precommissural nucleus ACN, including oxytocin neurons, that were more active during nurture.

The hormones oxytocin and prolactin are essential for lactation, a characteristic of mammals. Knockout mice of these molecules cannot lactate, but their nurturing behavior is not much impaired.Before the evolution of breastfeeding, the mother-child relationship evolved, and hormones are not considered essential for this.

5. Molecular Mechanisms of the Parental Care Experience

In parenting mice, the ERK-FosB-SPRY1/Rad signaling pathway is activated in the neurons of the MPOA. When this pathway is inhibited, mothers are able to parent their young, but young female mice are unable to learn to parent their young.（Kuroda et al, 2007,2010）

	Is parenting “maternal instinct”? As with eating and sexual behavior, good parenting requires the development of neural circuits through experience and learning.
	◆ Experience gained from social relationships early in life ◆ Experience of watching and learning from others who are raising children ◆ Experience actually interacting with children

Especially in primates, including humans, all three types of experience are very important. Of these, ERK-Fos signaling is involved in “actually interacting” experiential learning.

6. The “awakening paternal instincts ” of the mice

Young male mice do not raise their pups and may bully them. However, when they live with a female and become fathers, they raise their pups as well as mothers do. At this time, the father mice not only take care of their own pups but also shows affection to other mice's pups. It is strange that even though the stimulus of other offspring is the same, experience changes something in the male's brain, and paternal instincts naturally awaken. 

This phenomenon of "awakening paternal instincts" is also observed in lions and monkeys, but the mechanism was unknown. Therefore, when we investigated the brain regions involved in male parenting and infanticidal behavior, we found the ACN, MPOA (especially cMPOA), and BST (especially BSTrh).

Inhibition of BSTrh reduces litter killing in young males, and inhibition of cMPOA renders the fathers unable to raise their pups.

Artificial activation of cMPOA by optogenetics or pharmacogenetics also reduced brood killing in young males. cMPOA and BSTrh are thought to act antagonistically to determine whether to choose parenting or infanticide.

Furthermore, from the activity of BSTrh and cMPOA, it is possible to predict whether the male has  or attacked the pups.