Fast modulation of olfactory signaling and behavior by the mouse anterior olfactory nucleus

Medinaceli Quintela, Renata; Rothermel, Markus (Thesis advisor); Kampa, Björn M. (Thesis advisor)

Aachen : RWTH Aachen University (2022, 2023)
Dissertation / PhD Thesis

Dissertation, RWTH Aachen University, 2022


Our sensory organs continuously sample a vast amount of information from a highly multisensory environment. However, our perception is not solely based on external cues but is also substantially shaped by so-called top-down input. Top-down projections connect higher-order brain areas to more upstream structures to actively tune sensory processing in a context-dependent manner and tailor behavioral responses accordingly. Although often neglected, their presence is an inherent feature of every sensory pathway. The olfactory system is no exception as modulation of olfactory information already occurs at its earliest processing stage, the olfactory bulb (OB). The OB is heavily innervated by cortical top-down projections originating in the piriform cortex (PC) and, to a greater extent, in the anterior olfactory nucleus (AON). Functionally, not much is known about AON top-down projections, as so far only a handful of publications attempted to characterize them. Here, we investigated AON‘s contribution in shaping early olfactory processing and olfactory-dependent behaviors using optogenetics in combination with state-of-the-art recording techniques. In anesthetized mice, we selectively activated ChR2-expressing AON projections in the OB in parallel with multichannel electrophysiological recordings of sensory-evoked mitral/tufted cell (MTC) responses. We demonstrated that optical activation of AON fibers significantly attenuated spontaneous as well as odor-evoked MTC spiking. Similar results were obtained when recording MTC responses in awake mice following activation of AON somata, thereby demonstrating that AON-driven modulation of OB activity persists across brain states. On the other hand, AON photoinhibition resulted in increased MTC activity, thus indicating that AON top-down input can bidirectionally modulate OB output. The effect of AON-driven modulation was further investigated on a behavioral level. Here, optical AON activation robustly impaired behavioral odor responses, while AON inhibition reduced olfactory discrimination accuracy. While a causal link between the physiological and behavioral changes is yet to be determined, we tested the feasibility of an "all-optical" strategy to record MTC activity in response to AON stimulation in awake behaving mice using widefield imaging and two-photon microscopy. By imposing strong inhibition on OB output and disrupting the transmission of olfactory signals to the olfactory cortex our results highlight the AON as a potent modulator of olfactory perception/olfactory-driven behaviors.


  • Department of Biology [160000]
  • Department of Molecular and Systemic Neurophysiology [162320]