How genes influence social behavior in animals

Mara Cowen was the lead author on this study. Mara was co-mentored by Dr. Mike Hart and Dr. David Raizen and researched the effect of mutations in the autism-related gene, Neurexin, on aggregation, stress response, sleep, and neuronal morphology in C. elegans as part of the Autism Spectrum Program of Excellence (ASPE). When not in the lab, Mara can be found traveling, baking, binge-watching Netflix, and going to breweries with her rescue Australian Shepherd, Crispr!

or technically,

Conserved autism-associated genes tune social feeding behavior in C. elegans

[See Original Abstract on Pubmed]

Authors of the study: Mara H. Cowen, Dustin Haskell, Kristi Zoga, Kirthi C. Reddy, Sreekanth H. Chalasani & Michael P. Hart

Most people, including myself, love having lunch with their friends. This kind of behavior is known as social feeding and is common across many animals including most species of birds, fish, mammals, and even insects. Social feeding, in addition to other behaviors that animals exhibit, is controlled by the nervous system which is made up of nerve cells called neurons. Despite the fact that different animal species have different nervous systems, social feeding occurs almost universally across the animal kingdom. This begs the question: what in the nervous system makes it such that animals prefer social feeding as compared to eating alone? Mara, a former NGG graduate student, and her lab, thought that perhaps this was due to changes in an individual’s genes - the blueprints for how the body should grow, develop, and function.

To explore this question of how genes might influence social feeding, Mara studied the behavior of an animal called C. elegans, which is a worm-like animal about the size of a grain of sand. Despite their small size and relatively simple nervous system, these worms can perform many different social behaviors, including social feeding. Social worms tend to clump up together, or aggregate, while eating. In addition to exhibiting the behavior that Mara is interested in, C. elegans are commonly used in labs because experimenters have very precise control over the genes that the worms express. Worms that express a particular set of genes are referred to as a strain. This makes C. elegans the perfect animal to study how genes influence social feeding behavior.

Mara began her study using two worm strains that show opposite social feeding behaviors - one strain that shows consistent social feeding, the social control strain (Figure 1A), and one strain that prefers to eat alone, the solitary control strain (Figure 1D). For both strains, she counted the number of worms that aggregated and the number of worms that did not. She found that 78% of the social control worms ate together, whereas only 4% of the solitary control worms ate together.

Figure 1. The effect of different genes on social feeding behavior in C. elegans.

Now that she has these two worm strains as reference points, Mara’s main goal was to understand how different genes affected social feeding behavior. However, most animals, including C. elegans, have tens of thousands of genes - how was Mara to know which genes would be involved in social feeding behavior? This is where she and her lab used insight from past studies of human social conditions, such as autism. Recent work studying autism found that the neurexin gene and the neuroligin gene were highly associated with autism. Traditionally, these two genes were known to only be involved in allowing neurons to connect with one another. More recent work exploring the function of these genes suggests that they also play a role in controlling social behavior. Therefore, Mara asked whether the neurexin and neuroligin genes could also be playing a role in social feeding in C. elegans and, if so, how. Indeed, when Mara disrupted the neuroligin or the neurexin gene in the social control strain, the worms displayed significantly less social feeding behavior (Figure 1B). Interestingly, if you disrupt both the neuroligin gene and the neurexin gene, the worms show even less social feeding behavior than if you disrupted just one of them (Figure 1C).

Next, Mara and her group wanted to take a closer look at where exactly the neurexin and neuroligin genes were acting to support social feeding behavior. Based on previous work, they knew that a few select neurons are particularly important in social feeding. Interestingly, Mara found that these neurons express the neurexin and neuroligin genes and that expressing neurexin in just two of these neurons restored social feeding behavior. Further, Mara wanted to know how neuronal communication was affected in worms that lacked these genes. She found that in social worms without neurexin there were fewer points of connections, known as synaptic puncta. Additionally, these neurons release a chemical called glutamate which is known to be very important for neurons to signal to one another. Mara and her group found that more glutamate was released from one particular social feeding neuron in the social control group and less glutamate was released from that same neuron in the solitary control group. Mara’s work suggests that increased neural communication, be that number of synaptic puncta or amount of glutamate, was associated with increased social feeding behavior. Therefore, this work provides insight into how genes that regulate the connection between neurons impact social behavior.

Taken together, Mara’s results point to multiple underlying factors that have a direct impact on social feeding behavior. In particular, she identified neurexin, neuroligin, and glutamate as key biological components that are important for this behavior. And importantly, some of these same biological factors have been implicated in human neurodevelopmental conditions, such as autism. Future experiments will build off Mara’s work to get a clearer picture of how social behavior emerges from these biological factors and even perhaps lead the way to the development of therapeutics to help improve people's lives.

About the brief writer: Jafar Bhatti

Jafar Bhatti is a PhD Candidate in the lab of Dr. Long Ding / Dr. Josh Gold. He is broadly interested in brain systems involved in sensory decision-making.

Interested In learning more? Check out the full paper here!