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Olfactory-limbic connection: from scents to behavior

Subject Area Cognitive, Systems and Behavioural Neurobiology
Molecular Biology and Physiology of Neurons and Glial Cells
Term from 2020 to 2024
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 445965029
 
Final Report Year 2025

Final Report Abstract

Social behaviors are a crucial aspect of life, encompassing conflictive and cooperative interactions essential for health, survival, and reproduction. Specific sensory stimuli, particularly olfactory cues, can trigger these behaviors, but the underlying neural circuits remain poorly understood. In our ANR-DFG project, in collaboration with Dr. Pablo Chamero (Agence Nationale de la Recherche / French National Research Agency), we propose investigating the molecular, cellular, and neural basis of olfaction-mediated social behaviors. Our goal is to elucidate how olfactory signals are processed in the brain, from their initial detection in the olfactory bulb to their transmission to key regions involved in social behavior. We used a multi-disciplinary approach, combining cutting-edge techniques such as two-photon imaging, viral circuit tracing, and gene targeting. Our studies investigated how olfaction influences social behaviors, including parental care, and the impact of aging and disease on social odor perception. To this end, we successfully established a long-term imaging approach in our laboratory, which enabled us to image odor signals from the OB through a chronically implanted window for several months. Using viral tracers, we aimed to identify the neural circuits that connect the olfactory bulb to higher olfactory cortex neurons in the medial amygdala and the bed nucleus of the stria terminalis. We tested adeno-associated viruses obtained from commercial vendors (Addgene) for their ability to label the circuits of interest. However, tracing from these brain areas was technically challenging and did not produce reproducible results, as AAV tracing from the amygdala did not provide a sufficient number of labeled cells in the OB. Therefore, we pursued our original proposed goal and tested different versions of genetically encoded calcium indicators (GCaMP)-expressing transsynaptic pseudorabies (PrV) and rabies virus (RV) that were custom-made for us by our collaboration partners at the Federal Research Institute for Animal Health in Riems. To validate the viruses, we tested their capacity for functional expression of the cloned calcium indicator in diverse cell types in vitro and assessed their effectiveness as in vivo circuit tracers by examining their ability to selectively label OB output neurons that relay olfactory signals to the amygdala. Different versions of GCaMP-expressing PrV did not yield a sufficient number of infected cells, either in vitro or in vivo. GCaMP-expressing rabies virus, in comparison, exhibited reasonable infection rates and fast and sufficient calcium signals when tested in vitro. Due to external circumstances, we have not yet been able to test this virus in vivo. This study aimed to uncover the neural and molecular mechanisms underlying olfaction-mediated social behaviors, focusing on parental care and the effects of aging and disease on social odor perception. The findings demonstrate significant progress toward these objectives, providing critical insights into the neural circuits and sensory pathways influencing olfactory-driven social behaviors.

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