Sensory systems allow an animal to detect relevant environmental information and react to it with adjusted adequate behavior. In rodents, olfaction is a key chemosensory modality that enables diverse essential functions such as food detection/selection and social interactions. To fulfil these functions the olfactory system has to detect and discriminate between odorants from a rich and varied olfactory environment.
Notably, the response properties of neurons to external stimuli in the OB are, as a function of the mouse’ behavioral state, dynamically modulated. Top-down modulation of neurons in the OB is significantly mediated by centrifugal projections from the olfactory cortex and basal forebrain centrifugal projections from the horizontal diagonal band/magnocellular preoptic nucleus (HDB/MCPO). Using a rabies virus-based mono-transsynaptic tracer system we have recently investigated the neuronal connectivity between HDB/MCPO and OB and found beside the prominent cholinergic, also GABAergic and glutamatergic projections to the OB. How these different neuronal subtypes are spatially arranged and differentially contribute to OB neurons’ top down modulation during olfactory-driven behaviors is largely unknown.
In the proposed project we will use novel recombinant adeno-associated virus (rAAV)-based, as well as rabies virus-based mono-transsynaptic tracing tools to establish a comprehensive neuroanatomic profile of the cells and circuits structuring the HDB/MCPO to OB network. We will then use cell-type and brain region specific optogentic (miniSOG) and pharmacogenetic (DREADD) tools to spatio-temporally manipulate HDB/MCPO afferents in the OB during odor-, and social discrimination tasks. (M. K. Schwarz).
To functionally characterize the effects of HDB/MCPO top down modulatory activity on the circuit level, we will carry out Calcium-imaging in OBs of transgenic mice expressing GCaMP6 selectively in mitral cells after conditional silencing of HDB/MCPO neuronal populations (cholinergic, GABAergic, glutamatergic) in awake head-fixed mice during odor- and social discrimination tasks. To directly monitor the activity of HDB/MCPO neurons, we will install grin-lenses that will enable us to analyze the spatiotemporal activity properties of individual HDB/MCPO neurons during social recognition and odor discrimination (M. Fuhrmann).
In summary, the proposed project will reveal if the HDB/MCPO is directly and differentially modulated during active odour sampling and if this feed-back loop can actively modulate odour processing and different olfactory-driven behaviours.