The activity of sensory circuits is shaped by neuromodulators, which can have downstream consequences for both sensorimotor integration and behavioral output. Recent evidence indicates that brain-derived estrogens (‘neuroestrogens’) can act as local circuit modulators in the songbird auditory forebrain. Specifically, neuroestrogens fluctuate in the auditory caudomedial nidopallium (NCM) during social interactions and in response to song stimuli. Within minutes of elevation, neuroestrogens also enhance auditory response properties of NCM neurons, and acute blockade of estrogen production in NCM disrupts behavioral song discrimination. Here, we test the hypothesis that fluctuating neuroestrogens within NCM influence stimulus selectivity in a downstream sensorimotor nucleus (HVC) that receives indirect auditory input from NCM. Dual extracellular recordings coupled with retrodialysis delivery show that song-selectivity in HVC is rapidly enhanced by increasing neuroestrogens in NCM in adult males. Conversely, inhibiting neuroestrogen production in NCM causes a rapid decline in song-selectivity in HVC, demonstrating the endogenous nature of this modulatory network. By contrast, HVC selectivity is unaffected by neuroestrogen delivery to either nearby caudomedial mesopallium (CMM) or into HVC itself, indicating that neuroestrogen actions are restricted to NCM. In juvenile males, identical E2 treatment in NCM also does not alter HVC selectivity, consistent with a developmental maturation of the auditory network. Lastly, the rapid actions of estrogens leading to enhanced HVC selectivity appear to be mediated by membrane-bound receptors in NCM. These findings indicate that steroid-dependent modulation of sensory processing is not locally restricted and can be transmitted transynaptically to influence downstream sensorimotor and premotor targets.

Highlights d Genetic inactivation of Otop1 in mice eliminates proton currents in taste cells d Otop1-KO mice have severely attenuated cellular responses to acids d Otop1-KO mice have severely attenuated gustatory nerve responses to acids d Otop1 is a sour taste receptor

Mechanosensory neurons across physiological systems sense force using diverse terminal morphologies. Arterial baroreceptors are sensory neurons that monitor blood pressure for real-time stabilization of cardiovascular output. Various aortic sensory terminals have been described, but those that sense blood pressure are unclear because of a lack of selective genetic tools. Here, we find that all baroreceptor neurons are marked in Piezo2-ires-Cre mice and then use genetic approaches to visualize the architecture of mechanosensory endings. Cre-guided ablation of vagal and glossopharyngeal PIEZO2 neurons eliminates the baroreceptor reflex and aortic depressor nerve effects on blood pressure and heart rate. Genetic mapping reveals that PIEZO2 neurons form a distinctive mechanosensory structure: macroscopic claws that surround the aortic arch and exude fine end-net endings. Other arterial sensory neurons that form flower-spray terminals are dispensable for baroreception. Together, these findings provide structural insights into how blood pressure is sensed in the aortic vessel wall.

It is now clear that estrogens are not just circulating reproductive hormones, but that they also have neurotransmitter-like properties in a wide range of brain circuits. The view of estrogens as intrinsic neuromodulators that shape behavior has been bolstered by a series of recent developments from multiple vertebrate model systems. Here, we review several recent findings from studies of songbirds showing how the identified neural circuits that govern auditory processing and sensorimotor integration are modulated by the local and acute production of estrogens. First, studies using in vivo microdialysis demonstrate that estrogens fluctuate in auditory cortex (30-min time bin resolution) when songbirds are hearing song and interacting with conspecifics. Second, estrogens rapidly boost the auditory-evoked activity of neurons in the same auditory cortical region, enhancing auditory processing. Third, local pharmacological blockade of estrogen signaling in this region impairs auditory neuronal responsiveness as well as behavioral song preferences. Fourth, the rapid estrogen actions that occur within the auditory cortex can propagate upstream (transsynaptically) to sensorimotor circuits to enhance the neural representation of song. Lastly, we present new evidence that the receptor for the rapid actions of estradiol is likely in neuronal membranes, and that traditional nuclear estrogen receptor agonists do not mimic these rapid actions. Broadly speaking, many of these findings are observed in both males and females, emphasizing the fundamental importance of estrogens in neural circuit function. Together, these and other emergent studies provide support for rapid, brain-derived estrogen signaling in regulating sensorimotor integration, learning and perception.