Sensory neurons of the vagus nerve monitor distention and stretch in the gastrointestinal tract. We used genetically guided anatomical tracing, optogenetics and electrophysiology to identify and characterize two vagal sensory neuronal subtypes expressing Prox2 and Runx3. We show that these neuronal subtypes innervate the esophagus where they display regionalized innervation patterns. Electrophysiological analyses showed that they are both low threshold mechanoreceptors but possess different adaptation properties. Lastly, genetic ablation of Prox2 and Runx3 neurons demonstrated their essential roles for esophageal peristalsis and swallowing in freely behaving animals. Our work reveals the identity and function of the vagal neurons that provide mechanosensory feedback from the esophagus to the brain and could lead to better understanding and treatment of esophageal motility disorders.

The taste system detects 5 major categories of ethologically relevant stimuli (sweet, bitter, umami, sour and salt) and accordingly elicits acceptance or avoidance responses. While these taste responses are innate, the taste system retains a remarkable flexibility in response to changing external and internal contexts. Taste chemicals are first recognized by dedicated taste receptor cells (TRCs) and then transmitted to the cortex via a multi-station relay. I reasoned that if I could identify taste neural substrates along this pathway, it would provide an entry to decipher how taste signals are encoded to drive innate response and modulated to facilitate adaptive response. Given the innate nature of taste responses, these neural substrates should be genetically identifiable. I therefore exploited single-cell RNA sequencing to isolate molecular markers defining taste qualities in the taste ganglion and the nucleus of the solitary tract (NST) in the brainstem, the two stations transmitting taste signals from TRCs to the brain. How taste information propagates from the ganglion to the brain is highly debated (i.e., does taste information travel in labeled-lines?). Leveraging these genetic handles, I demonstrated one-to-one correspondence between ganglion and NST neurons coding for the same taste. Importantly, inactivating one ‘line’ did not affect responses to any other taste stimuli. These results clearly showed that taste information is transmitted to the brain via labeled lines. But are these labeled lines aptly adapted to the internal state and external environment? I studied the modulation of taste signals by conflicting taste qualities in the concurrence of sweet and bitter to understand how adaptive taste responses emerge from hardwired taste circuits. Using functional imaging, anatomical tracing and circuit mapping, I found that bitter signals suppress sweet signals in the NST via top-down modulation by taste cortex and amygdala of NST taste signals. While the bitter cortical field provides direct feedback onto the NST to amplify incoming bitter signals, it exerts negative feedback via amygdala onto the incoming sweet signal in the NST. By manipulating this feedback circuit, I showed that this top-down control is functionally required for bitter evoked suppression of sweet taste. These results illustrate how the taste system uses dedicated feedback lines to finely regulate innate behavioral responses and may have implications for the context-dependent modulation of hardwired circuits in general.

Multisensory responses are ubiquitous in so-called unisensory cortex. However, despite their prevalence, we have very little understanding of what – if anything - they contribute to perception. In this talk I will focus on audio-visual integration in auditory cortex. Anatomical tracing studies highlight visual cortex as one source of visual input to auditory cortex. Using cortical cooling we test the hypothesis that these inputs support audiovisual integration in ferret auditory cortex. Behavioural studies in humans support the idea that visual stimuli can help listeners to parse an auditory scene. This effect is paralleled in single units in auditory cortex, where responses to a sound mixture can be determined by the timing of a visual stimulus such that sounds that are temporally coherent with a visual stimulus are preferentially represented. Our recent data therefore support the idea that one role for the early integration of auditory and visual signals in auditory cortex is to support auditory scene analysis, and that visual cortex plays a key role in this process.

Mammalian babies are “sensory traps” for parents. Various sensory cues from the newborn are tremendously efficient in triggering parental responses in caregivers. We recently showed that core aspects of maternal behavior such as pup retrieval in response to infant vocalizations rely on active learning of auditory cues from pups facilitated by the neurohormone oxytocin (OT). Release of OT from the hypothalamus might thus help induce recognition of different infant cues but it is unknown what sensory stimuli can activate OT neurons. I performed unprecedented in vivo whole-cell and cell-attached recordings from optically-identified OT neurons in awake dams. I found that OT neurons, but not other hypothalamic cells, increased their firing rate after playback of pup distress vocalizations. Using anatomical tracing approaches and channelrhodopsin-assisted circuit mapping, I identified the projections and brain areas (including inferior colliculus, auditory cortex, and posterior intralaminar thalamus) relaying auditory information about social sounds to OT neurons. In hypothalamic brain slices, when optogenetically stimulating thalamic afferences to mimic high-frequency thalamic discharge, observed in vivo during pup calls playback, I found that thalamic activity led to long-term depression of synaptic inhibition in OT neurons. This was mediated by postsynaptic NMDARs-induced internalization of GABAARs. Therefore, persistent activation of OT neurons following pup calls in vivo is likely mediated by disinhibition. This gain modulation of OT neurons by infant cries, may be important for sustaining motivation. Using a genetically-encoded OT sensor, I demonstrated that pup calls were efficient in triggering OT release in downstream motivational areas. When thalamus projections to hypothalamus were inhibited with chemogenetics, dams exhibited longer latencies to retrieve crying pups, suggesting that the thalamus-hypothalamus noncanonical auditory pathway may be a specific circuit for the detection of social sounds, important for disinhibiting OT neurons, gating OT release in downstream brain areas, and speeding up maternal behavior.