Increased anxiety and decreased sociability induced by paternal deprivation involve the PVN-PrL OTergic pathway

Abstract

Early adverse experiences often have devastating consequences. However, whether preweaning paternal deprivation (PD) affects emotional and social behaviors and their underlying neural mechanisms remain unexplored. Using monogamous mandarin voles, we found that PD increased anxiety-like behavior and attenuated social preference in adulthood. PD also decreased the number of oxytocin (OT)-positive neurons projecting from the paraventricular nucleus (PVN) and reduced the levels of the medial prefrontal cortex OT receptor protein in females and of the OT receptor and V1a receptor proteins in males. Intra-prelimbic cortical OT injections reversed the PD-induced changes in anxiety-like behavior and social preferences. Optogenetic activation of the prelimbic cortex OT terminals from PVN OT neurons reversed the PD-induced changes in emotion and social preference behaviors, whereas optogenetic inhibition was anxiogenic and impaired social preference in naive voles. These findings demonstrate that PD increases anxiety-like behavior and attenuates social preferences through the involvement of PVN OT neuron projections to the prelimbic cortex.

eLife digest

Parental care early in life is essential for normal development of the brain in humans and some other animals. It also lays the ground work for healthy behaviors later in life. Many studies have looked at the importance of a mother’s care, but less attention has been paid to the role played by fathers. Research shows that children who grow up without a father are at risk of emotional and behavioral problems later in life. But it is not clear how missing a father’s care affects brain development.

Oxytocin, a chemical produced by a part of the brain called the paraventricular nucleus, plays a key role in parental bonding. Another part of the brain called the prelimbic cortex regulates many emotions and many complex behaviors. Studying animals, like the mandarin vole, that form strong bonds with both parents is one way to learn more about how the loss of paternal care affects oxytocin or emotional and behavioral health.

Now, He et al. show that mandarin voles raised without a father are more anxious and socialize less with other voles than those raised with a father. The voles deprived of paternal care also have fewer oxytocin-producing cells in the paraventricular nucleus and fewer receptors for oxytocin in the prelimbic cortex. Injecting oxytocin into the prelimbic cortex eliminated the anxious and antisocial behavior seen in the voles lacking paternal care. Using a technique called optogenetics to restore the release of oxytocin in the prelimbic cortex reduced anxious behavior and restored normal social interactions. Using the same approach to interfere with communication between the paraventricular nucleus and prelimbic cortex in voles raised with a father also triggered anxious and antisocial behavior.

The experiments reveal that fathers play an important role in brain and behavioral development in mandarin voles. He et al. show that a lack of paternal care leads to deficits in oxytocin and a poor communication between the paraventricular nucleus and prelimbic cortex that contribute to emotional and social abnormalities in the voles. More studies are needed to determine father’s care has similar effects in humans. But if this relationship is confirmed, it might lead scientists to develop new strategies for treating psychiatric disorders in people deprived of paternal care.