Neural activity in the olfactory bulb evoked by aversive, non-olfactory stimuli and patterned by respiration
Creators: name: Perkins, Keith Anthony
Publisher: name: No Publisher Supplied
Year: 2025

description: Sensory circuits in the brain change over time to reflect the organisms learned knowledge about the sensory world, including the incorporation of information about stimulus meaning or importance. For example, when a person or animal model learns that an odor predicts an aversive electric shock, the olfactory system itself undergoes extensive neuroplasticity including in the olfactory sensory neurons in the nose and in the brain’s olfactory bulb. This dissertation reports findings using optical neurophysiology in a mouse model to explore how various populations of neurons in the early olfactory know about aversive, non-olfactory stimuli and how they interact with respiratory activity. These experiments revealed that multiple populations of neurons in the mouse olfactory bulb respond strongly to aversive electrical stimulation on the tail. The earliest and largest responses were observed in populations of periglomerular (PG) interneurons, with later responses in short axon (SA) cells and mitral/tufted cells (M/T), showing that the tailshock-evoked activity propagates through the circuit and evolves over time. Similar results were observed using direct electrical stimulation of the trigeminal nerve, which communicates odor-evoked feelings of pain (e.g. ammonia) and temperature (e.g. warming cinnamon or cooling mint) from the nose to the brain via the trigeminal ganglion rather than the olfactory nerve. This illustrates that the somatosensory-evoked responses in the olfactory bulb can be evoked by facial, cranial nerve-mediated stimuli and non-facial, spinal nerve-mediated stimuli.Aversive stimulation typically evokes a sharp inhalation, even in these sedated mice, and the somatosensory-evoked responses observed in the olfactory bulb were frequently (though not exclusively) time-locked to this initial inhalation. However, the spatiotemporal patterns of these responses differed markedly from odor-evoked responses (including not being confined to specific olfactory bulb glomeruli) and no shock-evoked responses were observed in the population of axon terminals from the olfactory sensory neuron (OSNs) that compose the olfactory nerve. Somatosensory-evoked inhalation of background odors is thus an insufficient mechanism for the observed olfactory bulb response. However, respiratory-linked oscillations are a major feature of neural activity in the olfactory bulb, and all four neuronal populations (OSN, PG, SA, and M/T) exhibited robust oscillatory behavior in the absence of explicit odor presentation. This included prominent respiration-coupled oscillations that were reduced when intranasal airflow was eliminated by shunting the mouse’s breathing through a tracheal tube instead of through the nose, though surprisingly they were rarely eliminated entirely even in the OSNs themselves. Ongoing neural activity in the olfactory bulb is thus normally coupled to the respiratory rhythm through a combination of peripheral airflow and centrifugal signaling. Similarly, we observed that somatosensory-evoked activity in the olfactory bulb was usually hugely reduced in PG, SA, and M/T cell populations but that clear somatosensory-evoked responses sometimes persisted and remained respiration-locked despite the total absence of intranasal airflow. Unilateral naris occlusion also greatly reduced shock-evoked activity in the olfactory bulb ipsilateral to the occlusion, but the effect was similarly incomplete. Taken together these experiments demonstrate that like ongoing oscillatory activity, shock-evoked activity in the bulb may reflect the interplay of a centrifugally-originating signal with peripheral input from the nose.The convergence of information about odors and aversive somatosensory stimuli like tailshock suggests that odor-specific, learning-induced neuroplasticity could occur via local interactions in the olfactory bulb. These interactions may also play a role in linking olfactory percepts with their chemesthetic features, such as the smell and burn of ammonia.