The vassopressinergic system in the olfactory bulb: Neuronal mechanisms of social odor discrimination

• Applicants: Professorin Dr. Veronica Egger; Dr. Michael Lukas
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Cognitive, Systems and Behavioural Neurobiology
• Term: from 2016 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 336677558

The neuropeptide vasopressin (VP) is a major mediator of vertebrate social behavior, best described within key limbic brain areas, like the hypothalamus and the amygdala. However, the intrinsic VP system in the olfactory bulb and therewith its influence on social odor processing are relatively unexplored. So far, bulbar VP cells are described as glutamatergic external tufted cells that innervate individual glomeruli with a dendritic tuft, and VP has been shown to reduce output from the principal mitral cells. This action is most likely required for individual social odor discrimination. The detailed physiological mechanisms, e.g. precisely how VP mediates the encoding of specifically social odors on the cellular and the systemic level of the bulb, are far from being understood. Further, there exists a conceptual gap between VP neuromodulation on the cellular level and how these mechanisms actually account for the maintenance of social memory. Here we present a detailed working hypothesis based on first preliminary data that could explain how social-odor-specific signaling is implemented and stored by the VP system at the cellular level. To test this concept the bulbar VP system needs to be characterized in several respects, i.e. (1) cellular and subcellular anatomy, (2) network interactions, and (3) coupling to behavior.Thus, we first plan to identify synaptic partners of VP cell dendrites and axons at the histological and ultrastructural level, with a focus on glomerular interactions. Although excitatory bulbar neurons with glomerular tufts are typically excited by olfactory nerve input, we have found that GFP+-VP cells in a transgenic rat line receive biphasic input upon olfactory nerve stimulation with an early, strong GABAergic component, whose precise origin needs to be further explored. According to our concept, the delayed, weaker excitatory inputs should coincide with additional excitatory social-specific inputs to trigger local release of VP. Candidates are long-range inputs from the accessory olfactory bulb and the anterior olfactory nucleus. These structures are known to modulate odor signaling in the main olfactory bulb, in particular in the context of odor-dependent social behaviors. We also plan to monitor the impact of the intrinsic VP system on bulbar network activity, using Ca2+ population imaging in acute slices. Finally, we plan to test the involvement of the previously established cellular candidate mechanisms in actual social behavior. Briefly, we will pharmacologically modulate the social discrimination abilities of juvenile rats by manipulating specifically the bulbar VP system, including distinct VP receptor and GABAA receptor subtypes.We expect that insights into the cellular underpinning of the operation of the bulbar VP system in odor-guided social behavior will also shed light onto the cellular mechanisms of VPergic control of cortical and limbic brain structures during social cognition in general.

• DFG Programme: Research Grants