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    Top-down modulation of olfactory bulb sensory processing
    Dr. Markus Rothermel (RTWH Aachen)
    Top-down modulation of olfactory bulb sensory processing
    The neuronal representation of an external stimulus in sensory brain areas is not solely determined by sensory input but also strongly influenced by general brain state (wakefulness/sleep, attentiveness, arousal etc.). Modulations of brain state are mainly mediated by so called top-down inputs. Top-down systems are specific brain areas involved in cognitive function that can access goal- or target-directed as well as multimodal information and are thought to adapt sensory systems to the state of the animal and its requirements. Top-down systems have the potential to modulate the sensory information stream on multiple levels, ranging from lower to higher brain areas. However, modulations of early synaptic circuits would be of particular importance since they will affect all subsequent processing steps. Therefore, we are interested in how attentional systems modulate sensory processing by increasing the gain, sensitivity, or reliability of neural responses to sensory stimuli already at early processing stages.
    We investigate top-down modulations of early sensory processing in the mouse olfactory system. Top-down inputs to the first stage of odor information processing, the olfactory bulb, seem to be particular important as they outnumber direct synaptic sensory inputs. Yet, their influence on modulating sensory processing remains poorly understood - especially in a functional context.
    We found that top-down cholinergic projections from the basal forebrain regulate OB output by increasing the spiking frequency of mitral/tufted cells, the principal OB output neurons. This modulation was rapid and transient. Cholinergic enhancement of mitral/tufted cell odorant responses was robust and occurred independent of the strength or even polarity of the odorant-evoked response, indicating that cholinergic modulation adds an excitatory bias to mitral/tufted cell responses as opposed to increasing response gain or sharpening response spectra. These results are consistent with a role for the basal forebrain cholinergic system in dynamically regulating the sensitivity to or salience of odors during active sensing of the olfactory environment.
    Additionally we investigated projections to the OB from the anterior olfactory nucleus (AON), a major source of cortical feedback to the OB. We expressed GCaMP selectively in AON projection neurons allowing us to image GCaMP fluorescence signals from their axon terminals in the OB. Surprisingly, odorants evoked large signals that were transient and coupled to odorant inhalation both in the anesthetized and awake mouse, suggesting that feedback from AON to the OB is rapid and robust across different brain states. The strength of AON feedback signals increased during wakefulness, suggesting a state-dependent modulation of cortical feedback to the OB. Our results point to the AON as a multifunctional cortical area that provides ongoing feedback to the OB and also serves as a descending relay for other neuromodulatory systems.
    CIMH Mannheim, big lecture hall, 15:00-16:00