Connecting neurons for social defense

Abstract

Understanding neural circuits is more than knowing the pattern of projections and the chemical identity of a certain brain area. Sometimes neurons of the same nucleus and chemical identity project to different targets establishing parallel circuits that may be important to organize different aspects of the same behavior. A way to disentangle these parallel circuits is to look at developmental genes that determine which circuit this neuron is part of. The Medial nucleus of the Amygdala (MeA) is the most prominent recipient of projections from the accessory olfactory bulb which relays pheromonal information, important for social interactions. Research on the output of this nucleus based on neuronal chemical identity is being conducted in the project Fapesp #2016/18667-0 and although this study is key for developing new hypotheses, we cannot, so far, go deeper and separate different circuits within the MeA. With the aim of the present project "Identify and manipulate the parallel circuits in the medial amygdala underlying social defense", the groups of Professor Rüdiger Klein, neurodevelopmental specialist, and Assistant Professor Simone Motta, neuroanatomy specialist, are joining forces to dissect the different pathways from MeA to other brain regions responding to social stress. For this, we are planning single-cell RNA sequencing in adult mice to identify transcriptomic cell types in the MeA and to investigate the correspondence between cell identity and axonal projections. With this in hand we will produce transgenic animals and use optogenetics, chemogenetics, genetic ablations and calcium imaging to manipulate specific MeA projections and analyze behavioral responses. The Klein and Motta groups have the necessary knowledge of gene manipulation, functional imaging and neural circuit mapping tools to successfully complete this project. (AU)