Olfactory-limbic connection: from scents to behavior – LOFTER

Social behaviors, ranging from conflictive (e.g. aggression, infanticide) to cooperative (e.g. mating, mother-pup interaction), can be observed in all sexually reproducing animal species and are crucial for their health, survival, and reproduction. These behaviors are instinctual in the sense that they can be displayed without prior training in the presence of specific sensory stimuli, largely olfactory/pheromonal in nature. However, little is known about the underlying neuronal circuits encoding these behavioral responses. Therefore, we propose to define the molecular, cellular and neural basis of olfactory-mediated social behaviors – from circuit characterization to behavioral relevance. Specifically, we aim to determine how social signals are encoded in the olfactory bulb and relayed to different central brain areas in the limbic system that are considered important for social behavior. Next, we will study how these signals are processed by specific neurons in the limbic system that express the neurotransmitter GABA and the enzyme aromatase and identify specific social behaviors in which they are activated. We will use a multi-level approach combining two-photon and microendoscopic recordings in vivo, virus-based circuit tracing, gene targeting, and behavioral testing to elucidate the anatomical-physiological properties of olfactory circuits and to address their functional role in the control of social behavior. Social behaviors are stereotyped and thus developmentally hardwired, making them accessible to molecular genetic approaches to characterize the underlying neural circuits. We will execute three specific aims that are independent but interconnected. As a first step, we will identify the neural circuits from the olfactory bulb that target GABAergic and aromatase-expressing neurons in the medial amygdala and bed nucleus of the stria terminalis using viral tracers and determine the molecular identity of olfactory bulb neurons innervating this specific neural pathway. As a second step we will investigate the molecular range of these olfactory bulb neurons in response to chemosignals eliciting specific social behaviors using calcium imaging in vivo. Finally, we will functionally characterize the activity of GABA and aromatase positive neurons in different behavioral contexts in vivo. Taken together, this detailed study of neural pathways controlling well-defined olfactory-driven innate behaviors will provide an important landmark for understanding how the brain encodes complex behavior.