Distinct Orbitofrontal Neurons Interact to Regulate Feeding and Socializing in Mice

Post by Shireen Parimoo

What's the science?

Feeding and engaging in social behaviors are primal drives in humans and many other animals, including mice. These two behaviors have complementary roles and often interact to ensure survival - for example when food supply is maintained through social cooperation. These behaviors are regulated by overlapping neural circuitry in the brain, including neurons in the orbitofrontal cortex (OFC), a region involved in social interactions and reward-processing. The mechanism by which OFC neurons distinguish between  food and social stimuli, and regulate corresponding behaviors is currently unclear. This week in Nature, Jennings and colleagues investigated the effect of OFC neuron stimulation on social and feeding behaviors using calcium imaging and optogenetic techniques.

How did they do it?

Adult head-fixed mice (8-10 weeks old) were randomly placed into a control group or stimulation group. The authors injected a viral vector containing a green fluorescent calcium indicator into the OFC (expressed in neurons). In addition, they injected mice in the stimulation group with a viral vector containing a channelrhodopsin (light-activated ion channel). Neurons in mice in the stimulation group could then be activated in response to light, or ‘optogenetic stimulation’. The authors first sought to identify food-specific OFC neurons by providing mice with high calorie liquid rewards and comparing OFC activity in the 2 seconds before and after the reward was given. To examine the effect of these neurons on feeding behavior (i.e. licking rate), they optogenetically stimulated the neurons with 2-photon laser beams while mice were given the high calorie reward, low calorie reward, or no reward. Next, they sought to identify OFC neurons that were only responsive to social behavior (social-specific neurons) by placing a young (3 weeks old) or adult mouse in the same space as the adult mice and recording their interactions. These neurons were also optogenetically activated during the social interaction period and the effect on feeding and social behavior was measured. Finally, the authors determined the downstream effects of activating feeding- and social-specific neurons on un-stimulated neurons in the local OFC circuit in the absence of any stimuli (food reward or other mice).

What did they find?

Distinct groups of neurons were selectively active in response to high calorie food reward and social interaction. Optogenetic stimulation of food-specific neurons resulted in greater activation of those neurons and higher licking rate during reward presentation. However, increased licking was only observed in response to the high calorie reward - not the low-calorie reward or in the absence of any reward. This suggests that food-specific OFC neurons are selectively responsive to high calorie nutrients, not food rewards in general. Moreover, the activity of food-specific neurons also tracked the amount of licking – there was greater activity during increased bouts of licking and less activity during reduced bouts of licking. When the authors looked for social-specific neurons, they were able to identify different sets of OFC neurons active during social interaction between the head-fixed mice and the young mice, and the head-fixed mice and other adult mice. Stimulation of social-specific neurons led to increased neuronal activity and social interaction between the adult and young mice. However, it also led to reduced licking rate and feeding on the high calorie reward. This suggests that social-specific neurons have an inhibitory effect on the feeding-specific neurons in the OFC.

In the absence of any behavioral stimuli, optogenetic stimulation of both food- and social-specific OFC neurons resulted in increased activation of those neurons. Interestingly, it also had excitatory and inhibitory effects on neighboring, non-stimulated neurons. In particular, stimulation of social-specific neurons strongly inhibited non-stimulated food-specific neurons in the OFC. This means that although distinct groups of neurons are responsive to social and food reward stimuli, they interact with each other to affect both feeding and social behaviors.

What's the impact?

This study demonstrates how the interaction between distinct subsets of neurons in the OFC influences feeding and socializing behavior in mice. The results further clarify the functional role of the OFC and provide a deeper understanding of how complex and primal behaviors can arise from the interaction between distinct and shared neural circuitry in the brain.

Jennings et al. Interacting neural ensembles in orbitofrontal cortex for social and feeding behavior. Nature (2019). Access the original scientific publication here.