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.