Neural Representations of Social Homeostasis

Kay Tye has been a Professor in the Systems Neurobiology Laboratory and Wylie Vale Chair at the Salk Institute for Biological Studies since 2019. Her work has been recognised with several awards, including the technology Review’s Top 35 Innovator under 35 and the NIH Director’s New Innovator Award. Prof. Tye leads a team using a wide variety of cutting‐edge techniques, including cellular‐resolution recordings, behavioural assays, and optogenetics, to better understand the brain’s circuitry underlying emotion and motivation.

In her talk, Prof Tye showed the advances her lab has made in deciphering the neuronal mechanisms controlling social homeostasis.

Like homeostasis ‐ a process by which our body regulates, for instance, our body temperature upon temperature changes – social homeostasis is composed of a detector, a control centre and an effector which, in a coordinated manner, drive the adaptation of individuals to environmental changes (such as social isolation, or food seeking) within a social unit.

Some of the key questions that Tye lab is trying to answer are:

• How do individuals adapt to social changes?
• How do individuals maintain structure of their social unit upon environmental changes?
• How do environmental changes impact our social behaviour?

Main Findings

Tye lab has found that dopaminergic neurons of the dorsal raphe nucleus (DRN DA neurons) in mice are sensitive to social isolation, as they showed increased activity upon social contact following isolation. Interestingly, the activation of these DRN DA neurons using optogenetics recapitulated a loneliness‐like state by triggering sociability following acute isolation. These findings suggest that DRN DA neurons represent the effector system of social homeostasis.

However, loneliness is a subjective feeling, and subjective states are challenging to be analysed in animals. What is very well known in rodents is that they form social units with distinct social ranks including subordinates and dominants. These ranks, Tye lab found, can predict the behavioural effect of a change in a social environment modulating the detector, effector and control centre, and defining the final behaviour in social homeostasis (Matthews et al., 2016).

Importantly, and thanks to a newly developed wireless electrophysiological device, Tye lab has found that the rank is indeed encoded in the brain of the mice, as they identified distinct neuronal trajectories in the mPFC, that resemble the rank of the animals within the social unit and the outcome of a competition task (Padilla‐Coreano et al., 2020).

Social homeostatis

Once DRN DA neurons were identified as effectors of social homeostasis, Tye lab were able to identify a list of candidate regions to be control centres of social homeostasis using monosynaptic rabies tracing. Combined with optogenetics, they discovered that neurons in the lateral hypothalamus (LH) are connected to the DRN DA neurons and can drive hyper social behaviours (Nieh et al., Neuron 2016). Using an observational learning paradigm where a trained observer mouse sees the behaviour of a demonstrator mouse, and behaves like the demonstrator mouse, Tye lab has identified that the Anterior Cingulate Cortex/Basolateral Amigdala (ACC/BLA) circuit loop is involved in signal detection. (Allsop et al., Cell 2018).

Overcoming limitations

The observation of animal behaviours sometimes suffers from intrinsic subjectivity. In addition, traditional behaviour analyses reduce the amount of data acquired necessary for drawing statistically meaningful conclusions. In order to overcome these limitations, Tye lab has developed a tool called AlphaTracker. With this computer tool based on deep learning, Prof. Tye and colleagues can analyse the behaviour of multiple animals with high accuracy, capturing the social environment and clustering different social behaviours (Chen et al., bioRxiv 2020).

Conclusion

All in all, Prof. Kay Tye showed us the wide range of technical advances they have made to study social homeostasis and some key components of the neural mechanisms they have identified. Importantly, social interactions between individuals in a social unit, defined by the rank of individuals, plays an important role in the final outcome in social homeostasis.

References

Matthews, G.A., Nieh, E.H., Vander Weele, C.M., Wildes, C.P., Ungless, M.A., and Tye, K.M. (2016). Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation. Cell.

Padilla-Coreano et al. (2020). A cortical-hypothalamic circuit decodes social rankand promotes dominance behavior. Preprint.

Nieh, E.H., Vander Weele, C.M., Matthews, G.A., Leppla, C.A., Izadmehr, E.M., and Tye, K.M. (2016). Inhibitory Input from the Lateral Hypothalamus to the Ventral Tegmental Area Disinhibits Dopamine Neurons and Promotes Behavioral Activation. Neuron.

Allsop, S.A., Wichmann, R., Mills, F., Ba, D., Brown, E.N., and Tye, K.M. (2018). Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation. Cell.

Chen et al. (2020). AlphaTracker: A Multi-Animal Tracking and Behavioral Analysis Tool. bioRxiv.

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