Where social interaction meets spatial information

           Positive social interactions are often rewarding to humans. It is hypothesized that successful social interactions involve the same reward processing circuitry that underlies the pleasure we derive from food or money. Studies in rodents show that social interactions result in the release of dopamine, the neurotransmitter often associated with pleasure, in the nucleus accumbens (NAc), a small region buried deep in the brain (Fig. 1). An interesting observation from rodent studies is that mice often return to the same area they previously met another mouse. Before the advent of cell phones and Facebook (and perhaps even now), we probably did (do) the same, too. If you met interesting people at a bar, you are probably more likely to go that same bar again. But what are the neural circuits that make the association between social interaction and spatial location?

            In a recent study, entitled ‘Combined social and spatial coding in a descending projection from the prefrontal cortex’, Murugan et al (2017) identify a role for the connections from prelimbic cortex (PL) to NAc in driving this socio-spatial learning. The PL is implicated in learning and memory, the integration of sensory information and emotional regulation. The PL also regulates social interaction whereby the activation of PL neurons diminishes the time a mouse spends interacting with another mouse. The circuitry in the PL is complex and the PL projects to several brain areas. Three such areas are the NAc, the amygdala (Am) and the ventral tegmental area (VTA) (Fig.1). To determine which one of these projections is involved in social interaction, Murugan et al. use optogenetics to specifically activate distinct neuronal populations that project to either the NAc, Am or VTA. The reasoning with these experiments is that such artificial activation would disrupt the information flow between the two brain areas and impair the behavior that they support. The researchers determined that disrupting the activity of the PL-NAc pathway results in less social interaction. In contrast, the optogenetic disruption of PL-Am or PL-VTA pathways did not observably alter social interaction.

 Fig 1: The prelimbic cortex (PL) and its projections to the nucleus accumbens (NAc), Amygdala (Am) and ventral tegmental area (VTA) in the mouse brain.

Fig 1: The prelimbic cortex (PL) and its projections to the nucleus accumbens (NAc), Amygdala (Am) and ventral tegmental area (VTA) in the mouse brain.

              The authors then asked: what is the endogenous activity of these PL-NAc neurons during social interaction? Using calcium imaging of PL-NAc neuron they determined that these neurons are more active when the mouse interacts with another mouse (but not with objects). They also identify two subclasses of neurons: the ‘spatial’ neurons and the ‘social’ neurons. The spatial neurons are ones that respond when the mouse is in the same location in the box (regardless of whether another mouse or object was present) while the social neurons respond only when another mouse is present (regardless of location). The most interesting finding of this paper however was that there was yet another subset of these PL-NAc neurons that respond in the presence of another mouse only when the other mouse is in a particular location (Fig. 2). Furthermore, manipulating the activity of these neurons in a spatially specific manner during social interaction alters the likelihood of the mouse returning to a specific location after social interaction. For example, if you optogenetically inactivate PL-NAc when the mouse is in zone A but not in zone B, the mouse is less likely to spend time in zone A afterwards. Contrarily, if you activate PL-NAc when the mouse is socially interacting in zone A but not when its in zone B, the mouse is more likely to spend time in zone A afterwards.

 Fig. 2: Figure (adapted from figures in Murugan et al.) shows a summary of findings. PL-NAc neurons that response during social interaction. Some neurons show preference for mouse over object while some show preference for location. A number of neurons that show an interesting preference for mouse interaction only do so in a specific location – suggesting a sociospatial preference.

Fig. 2: Figure (adapted from figures in Murugan et al.) shows a summary of findings. PL-NAc neurons that response during social interaction. Some neurons show preference for mouse over object while some show preference for location. A number of neurons that show an interesting preference for mouse interaction only do so in a specific location – suggesting a sociospatial preference.

            Together, these findings suggest that the PL-NAc neurons are capable of combining social and spatial information to perhaps encode the information that tells a mouse the location where positive social interactions have occurred. Furthermore, since these projections alter activity in the NAc, a region heavily implicated in dopaminergic signaling, it is possible that the PL-NAc neurons alter dopamine signaling to form the association between location and pleasure – a possibility that requires further verification. There are many other open questions. What are the inputs to PL-NAc neurons that facilitate these associations? What happens in the case of a negative social interaction? Is this specific to social interactions or would other positive objects (food for example) induce a similar response in these PL-NAc neurons? What happens in cases of neuropsychiatric disorders where social interaction is impaired? Nevertheless, Murugan et al. have delineated a novel pathway and role for the PL in social interaction. The next time you go to your favorite bar again, perhaps you’ll remember that your PL is one reason you are there.