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Behind sociability? The medial prefrontal cortex

Sociability and the medial prefrontal cortex

Could it be possible to run a normal existence without social life? Indeed, sociability is an important aspect for individuals and social interactions build our lives. In fact, social interaction enhances quality of life and improves the stability of communities. Impaired sociability is a classical symptom observed in many neuropsychiatric disorders including autism, schizophrenia, depression, anxiety and generalized fear. Interestingly, many studies have pointed to the medial prefrontal cortex (mPFC), a brain area located in the ventromedial part of the frontal lobe, as a key region involved in the neural bases of sociability (Valk et al, 2015; Treadway et al., 2015; Frith et al., 2007).

The prelimbic cortex (PL) and the infralimbic cortex (IL), two subregions of the mPFC, have been strongly suggested to play an important role in the neural mechanisms underlying sociability as isolation rearing in rats results in impaired social behavior and structural modifications in the PL and IL. Isolation rearing is a neurodevelopmental manipulation that produces neurochemical, structural, and behavioral alterations in rodents that in many ways are consistent with psychiatric disorders such as schizophrenia, anxiety and depression. In particular, it has been shown that isolation rearing can alter the volume of mPFC, the dendritic length and the spine density of pyramidal neurons. However, the detailed mechanisms involved in sociability disorders remain elusive and poorly understood.


Altered mPFC activity after isolation

A recent article published in Plos ONE by Minami and colleagues aimed at measuring neural activity in the PL and IL of control and isolated rats during social interaction in order to determine whether there is neural activity related to social behavior in these areas. Experimentally, animals were divided equally into 2 groups at postnatal day (P) 21 and were housed either in groups (control, group-reared rats) or single-cage (isolation-reared rats).

Does isolation influence mPFC activity? To tackle this question, multiunit recording was used as technique to record neural activity in freely moving animals during social behavior testing. However, as stated by the authors, “the conventional technique requires that the animal be tethered to recording instruments with a cable of electrical wires” and this technical aspect may not facilitate natural and spontaneous social behavior in rats. To overcome these issue, Minami and colleagues used a wireless telemetry system to record the neural activity of a pair of freely moving rats during social interaction.

Behaviors in the social interaction test were categorized as sole (rats behave separately from each other), approaching (rat approaching the partner, reduction of distance), contact (which includes social exploration, aggressiveness and defensiveness), and leaving (rat leaving the partner).

Examples showing the behavior of the rats during the social interaction test. A, B: Sole behavior. Rats are behaving separately. The rat (no mark on its back) is exploring around by itself at the lower left corner of the test box and the partner (a black mark on its back) is resting at the lower right corner (A). Both rats are walking along the wall (B). C, D: Approaching behavior. The rat (arrow) is approaching the partner (C), and the partner (arrow) is approaching the rat (D). E–G: Contact behavior. Rats are sniffing (E) and boxing (F) each other, and the rat (arrow) is pinning and biting the partner (G). H, I: Leaving behavior. The rat (arrow) is leaving the partner (H), and the partner (arrow) is leaving the rat (I).

In control rats (non isolated ones) PL neurons showed increased firing rate during both approaching and contact behaviors, especially when the rat attacked the partner. In contrast to PL neurons, IL neurons showed increased firing only during leaving behavior. Several studies using electrophysiological recordings have shown that the increased firing of PL neurons is correlated with sustained fear, whereas the increased firing of IL neurons is correlated with the recall of extinction (Gilmartin and McEchron, 2005; Fitzgerald PJ et al., 2014).

What about isolated animals? Is neuronal activity different during social interaction?Isolation-reared rats showed an increased frequency and decreased duration of contact behavior in the present study. These results may be interpreted as that isolation-reared rats are interested in a novel partner but cannot continue contact behavior with the partner for a long period”, report the authors of the study. In agreement with this hypothesis, it has been reported that isolation-reared animals show a decreased duration of sociability as well as a hyperactivity to novel stimuli. Details analysis of the results revealed that PL neurons were characterized by increasing firing during approaching and contact behaviors (as reported in non-isolated rats). Conversely, IL neurons in isolation-reared rats did not show increased firing during leaving behavior (as observed in control animals), indicating that the increased firing of IL neurons observed during leaving behavior in group-reared rats is suppressed by isolation rearing.

The present data demonstrate the neural activity of the PL and IL during social interaction and the influence of isolation rearing on this activity. The differential effects of isolation rearing on the neural activity of the PL and IL may be one of the neural bases of isolation-induced behavior”, conclude Akira Mitani, the senior investigator of the study.

Further investigations are needed to fully understand the role of mPFC in sociability, perhaps paving the way to discovery of alternative solutions for neuropsychiatric disorders such as schizophrenia, anxiety and depression.

Any views expressed are those of the author, and do not necessarily reflect those of PLOS. 

Peppe-BWGiuseppe Gangarossa received his PhD in Biomedical Sciences, specialty Neuroscience, from the University of Bologna. He has been a visiting fellow at the Karolinska Institutet (Sotckholm, Sweden), the French Inserm (Montpellier, France) and the Collège de France (Paris, France). Giuseppe is currently Assistant Professor of Physiology at the University Paris Diderot. His main research topic is dopamine-related brain disorders. You can follow him on twitter @PeppeGanga

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