Human beings, like most mammals, need social interactions to develop and to learn. However, what drives us to make that move to connect, and how the brain encodes the reinforcing properties of social interaction, aren’t well understood. A team from the University of Geneva (UNIGE) studied the neurobiological mechanisms at play when two mice come into contact through learning a task. They observed that the motivation to invest in a social interaction is closely linked to the reward system, via the activation of dopaminergic neurons.

The results of their studies, they suggest, will make it possible to investigate possible dysfunction of these neurons in diseases such as autism, schizophrenia, or depression, which affect social interactions. “We will now be able to use these neurons as targets to find treatments for these diseases”, said Benoit Girard, PhD, a researcher in the Department of Basic Neuroscience. “Furthermore, the reward system is at the basis of the occurrence of addictive behaviours,” noted Camilla Bellone, PhD, professor in the Department of Basic Neuroscience at the UNIGE Faculty of Medicine and director of the National Centre of Competence in Research (NCCR) Synapsy. “Whether the excessive use of social media network could hijack the dopaminergic system and be at the basis of maladaptive behaviors toward social media is an interesting hypothesis that can be now tested.”

Bellone, Girard and colleagues reported on their findings in Nature Neuroscience, in a paper titled, “VTA dopamine neuron activity encodes social interaction and promotes reinforcement learning through social prediction error.”

Social interaction is an integral part of our daily lives, although the intention to interact with others requires an effort to act. So why do we do it? “Humans and animals are greatly motivated to interact with conspecifics,” the authors wrote. “Indeed, social interactions provide adaptive benefits, such as safety from predators, access to mates and cooperation … By increasing animal fitness, social behaviors are motivated through their adaptive benefits, and many social interactions are considered to be rewarding experiences both for animals and humans.”

But what is the mechanism behind the motivation we feel to engage with others? The authors further noted, “Although several studies have investigated the brain mechanisms underlying reward processes associated with food and drug consumption, the mechanisms of social reward remain largely unknown.”

Clinical and preclinical evidence that has accumulated over the past decade suggests that social interactions are rewarding experiences reinforced by social cues. To identify which neurobiological circuit is the basis of social interaction, the UNIGE researchers observed what happens in the brains of mice seeking contact with a conspecific. “In order to observe which neurons are activated during social interaction, we taught mice to perform a simple task that allows them to enter in contact with their fellows mice”, explained Bellone.

Two mice were placed in two different compartments and separated by a door. When the first mouse pressed a lever, the door opened temporarily, allowing social contact to be established with the second mouse through a grid. “As the experiment progressed, the mouse understood that it had to press the lever to join its fellow mouse,” continued Clément Solié, PhD, a researcher in Bellone’s team. “With this task, we can measure the effort the mice are willing to put to engage in interaction with conspecifics.”

Using electrodes, the scientists measured the activation of neurons in the ventral tegmental area (VTA) of the brain. “We found that the interaction between two mice, similarly to other natural reward, led to the activation of dopaminergic neurons, which are located within the reward system”, said Bellone.

These neurons release dopamine—the so-called pleasure molecule—which is crucial for several motivated behaviors. “What is even more interesting is that while during the first sessions, the dopaminergic neurons are activated when the mice interact with the conspecific, as soon as the mouse learn the association between the lever press and the interaction, the activity of dopaminergic neurons precede the reward”, added Girard. “Similarly, if the mouse presses the lever but the door does not open in the end, there is a sudden drop in the activity of the dopaminergic neurons, indicating great disappointment in the mouse”, noted Bellone. “This predicting signal is the neural substrate for learning and is crucial for social motivation.” Interestingly, further experiments indicated that optogenetic inhibition of VTA DA neurons in mice undergoing the task was sufficient to impair social reinforcement learning.

Additionally, the studies demonstrated a general habituation of VTA DA neuron activity when mice were repeatedly exposure to the same conspecific, although there was high heterogeneity in the individual neuronal responses. “Indeed, although some neurons responded only to the novelty, others were activated even when the stimulus became familiar,” the team wrote. “Our data show that different VTA

DA neurons are recruited to encode the novelty and the value of different social contacts. Overall, the large heterogeneity of VTA DA neuron responses, depending on whether the contacts are passive, unilateral or reciprocal, through exposure to a conspecific, reflect the high complexity of social behavior.” The collective data, the authors, pointed out, “suggests that individual neuronal populations within the VTA might contribute to the different building blocks that shape social interaction.”

Several psychiatric diseases such as autism, schizophrenia or depression are characterized by social dysfunctions and social motivation deficits are described in some of these patients. The study results indicated that these difficulties may result from dysfunctions within the reward system, and more precisely at the level of dopaminergic neurons. The authors finally concluded, “Together, these findings provide novel insights into the neuronal dynamics underlying social interaction and motivation and further suggest that VTA DA neurons might be the neural substrate for social learning.”

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