Optogenetic tool development

Optogenetics uses light-activated proteins to rapidly and reversibly modify the activity of living neurons. We have developed several new optogenetic tools, mostly focusing on light-gated silencing of neural and synaptic activity. We recently developed the mosquito-derived eOPN3 for presynaptic silencing, and PdCO is our new bidirectionally-switchable inhibitory optoGPCR, which allows a wide range of multiplexed applications. For more information on optogenetics, please see our recent reviews (e.g. Wiegert et al., 2017; Rost, Wietek et al., 2022). Our constructs (plasmids and AAV preps) are available on Addgene. Selected constructs are also available as packaged AAVs on the ETH viral vector facility.

Organization of cortical synaptic connectivity

Synaptic connections are the infrastructure on which neuronal computation takes place, and impaired synaptic connectivity can result in serious mental and neurological impairments. We are interested in understanding the organization of functional synaptic connectivity in the prefrontal cortex, how it changes with experience, and what are the mechanisms and implications of its disruption in neurodevelopmental disorders.

Functional dissection of prefrontal circuits

The prefrontal cortex is crucial for adaptive, goal-directed behavior, social cognition and long-term memory. We use electrophysiological recordings in behaving mice, optogenetic manipulations, calcium imaging and advanced photometry to dissect the dynamic involvement of these neurons in behavior. We showed that modulating the strength of communication between the amygdala and prefrontal cortex can lead to enhanced extinction of fear associations, and that mouse prefrontal neurons are particularly tuned to social odors. Our current work is aimed at further understanding the roles of prefrontal neural ensembles in long-term memory and social behaviors.

Cortical modulation of social behavior

Social behavior is crucial to the survival of all mammalian species, and is impaired in a wide variety of psychiatric disorders. Although many brain systems are involved in the regulation of social behaviors, prefrontal circuits are thought to play a dominant role in this process by guiding adaptive, context-dependent responses to social stimuli (see our recent review). We are interested in the mechanisms through which prefrontal circuits control social functions. By recording brain activity in mice engaged in social behavior, we can understand how the brain encodes social signals. Using genetic mouse models of autism, we are exploring the associated changes in circuit connectivity, circuit dynamics and behavior.

Early-life social behavior

Early life is a critical period for the development of social behavior in all mammals. We are interested in understanding the ontogeny of social behavior during early life through the prism of the mother-pup interaction. Apart from being critical for the safety and nutrition of the pre-weaning animal, mother-pup interactions are the first form of social communication in young mice. Using custom-built hardware and software, we are tracking the behavior and vocal communication of young pups. By combining this with minimally-invasive optogenetic techniques, we are able to target specific circuit elements and establish their role in mother-pup interactions.