Sniff-controlling Circuitry in the Parabrachial Nucleus - Project Summary / Abstract Olfaction provides animals with information about resource quality, conspecific identity, and environmental conditions. Most mammals use strong, fast, nasal inhalations, or sniffs, to mix odorants and draw them across the olfactory epithelium in the nose. Rapid sniffing bouts enable active sensing of odorants, providing many spatiotemporally localized samples per second. These bouts are highly dynamic, beginning and ending within single breaths, and, in mice, they can extend for minutes at a time. Sniffing, like all modes of breathing, is controlled by intrinsically oscillating circuitry in the ventral medulla, which receives top-down excitatory, inhibitory, and modulatory inputs. Despite the importance of dynamically controlling breathing and sniffing behaviors, it remains unknown how these inputs to the medulla are integrated to shape a fluid behavioral output. One of the input nuclei, the parabrachial nucleus (PBN), is well-known for its role in modulating respiration in response to acute threats like high CO2 and pain, as well as for its role in opioid-mediated breathing suppression. Additionally, it was recently shown that PBN stimulation modulates breathing in awake mice, and that tonic activity in PBN is important for the maintenance of baseline breathing. However, beyond that, it remains unclear how PBN’s activity might relate to the volitional control of breathing patterns, such as those underlying sniffing. We have leveraged our lab’s experience recording dopamine signaling in freely behaving mice to develop a similar setup capable of monitoring breathing and PBN neural activity. In preliminary experiments, I observed that PBN activity is correlated with sniffing behaviors, and that silencing PBN outputs can affect the expression of sniffing behaviors. Based on this evidence, I hypothesize that, rather than responding solely to interoceptive threats to modulate breathing, PBN integrates and transmits signals related to the volitional control of breathing, including sniffing. In Aim 1, I will test this hypothesis by modeling the relationship between PBN neural activity and breathing, and by testing the necessity of PBN signaling for sniffing behaviors. Then, in Aim 2, I will characterize the anatomical and functional roles of inputs to distinct PBN subpopulations that appear to play different roles in controlling breathing. Together, these experiments will characterize a novel aspect of PBN signaling, taking into account moment-to-moment neural activity, rather than relying on experimenter-delivered stimuli. Further, by characterizing PBN’s relationship to sniffing, they will begin to establish an understanding of the neural circuitry which controls active olfactory sampling.
