Exploring new roles of Robo2 in synaptic development, plasticity and hippocampal circuit function

Individual neurons in the brain have to form connections in a highly specific manner to allow for proper information processing in circuits. However, it is unknown how neurons switch their developmental state from axon and dendrite growth and guidance to synapse formation onto specific postsynaptic targets. The candidate?s extensive preliminary work identifies a novel role for the axon guidance effectors Slit and Robo2 in the control of excitatory synapses formed by CA2/CA3 axons (but not entorhinal axons) onto CA1 pyramidal neurons in vivo. The goal of this project is to test how this new role of Slit/Robo in synaptic specificity impacts circuit function and behavior, specifically spatial learning and memory in the hippocampus. The candidate will train to perform electrophysiology experiments in vitro and in vivo, combined with two-photon calcium imaging in awake behaving mice. Furthermore, the candidate will learn to perform Chromatin-immunoprecipitation (ChIP) and single-cell RNAseq to unravel yet another novel role of Robo2 in regulating transcription in response to synaptic plasticity. Candidate and Career Goals: The candidate has a strong background in cellular and molecular Neuroscience. In her postdoc, the candidate received basic training in in vivo 2P Ca2+ imaging that will be built on in this training grant. With this, the candidate is uniquely positioned to gain unprecedented insights in how molecular mechanisms of circuit development relate to their functional properties. Her long-term career goal is to establish an independent laboratory aimed at understanding how molecules serve context-dependent functions during development or in mature circuits. This is already exemplified by her work on unique roles for Slit-Robo signaling in axon guidance and synapse formation, now to be expanded to synaptic plasticity mechanisms. Career development plan: Dr Blockus will work with two co-mentors, Drs Franck Polleux and Attila Losonczy, who are international leaders in their respective fields. Dr Polleux is an expert on genetic, molecular and cellular mechanisms underlying circuit development and synaptic maturation. Dr Losonczy has unique expertise in interrogating hippocampal circuits in vivo in awake-behaving mice using two-photon calcium imaging and optogenetics. Additionally, the candidate has assembled a strong team of collaborators for training in electrophysiological techniques (Dr Steve Siegelbaum) as well as genomic regulation and single-cell RNAseq approaches (Dr Stavros Lomvardas). Furthermore, the candidate has appointed a career development advisor in Dr Carol Mason that will be instrumental in fostering the candidate?s career, especially with regards to promoting women in science.