Significance During conversations, we frequently alternate between listening and speaking. This involves withholding responses while the other person is vocalizing and rapidly initiating a reply once they stop. Similar exchanges also occur in other animals, such as songbirds, yet little is known about how brain areas responsible for vocal production are influenced by areas dedicated to listening. Here, we combined neural recordings and mathematical modeling of a sensorimotor circuit to show that input-dependent inhibition can both suppress vocal responses and regulate the onset latencies of vocalizations. Our resulting model provides a simple generalizable circuit mechanism by which inhibition precisely times vocal output and integrates auditory input within a premotor nucleus.

The superior colliculus (SC) is a midbrain structure that plays important roles in visually guided behaviors. Neurons in the SC receive afferent inputs from retinal ganglion cells (RGC), the output cells of the retina, but how SC neurons integrate RGC activity in vivo is unknown. SC neurons might be driven by strong but sparse retinal inputs, thereby reliably transmitting specific retinal functional channels. Alternatively, SC neurons could sum numerous but weak inputs, thereby extracting new features by combining a diversity of retinal signals. Here, we discovered that high-density electrodes simultaneously capture the activity and the location of large populations of retinal axons and their postsynaptic SC target neurons, permitting us to investigate the retinocollicular circuit on a structural and functional level in vivo . We show that RGC axons in the mouse are organized in mosaics that provide a single cell precise representation of the retina as input to SC. This isomorphic mapping between retina and SC builds the scaffold for highly specific wiring in the retinocollicular circuit which we show is characterized by strong connections and limited functional convergence, established in log-normally distributed connection strength. Because our novel method of large-scale paired recordings is broadly applicable for investigating functional connectivity across brain regions, we were also able to identify retinal inputs to the avian optic tectum of the zebra finch. We found common wiring rules in mammals and birds that provide a precise and reliable representation of the visual world encoded in RGCs to neurons in retinorecipient areas. HIGHLIGHTS High-density electrodes capture the activity of afferent axons and target neurons in vivo Retinal ganglion cells axons are organized in mosaics Single cell precise isomorphism between dendritic and axonal RGC mosaics Midbrain neurons are driven by sparse but strong retinal inputs Functional wiring of the retinotectal circuit is similar in mammals and birds

The ability to regulate vocal timing is a fundamental aspect of communicative interactions for many species, including conversational speech among humans, yet little is known about the neural circuitry that regulates the input-dependent timing of vocal replies. Exploring this topic in the zebra finch premotor area HVC, we identify feed-forward inhibition as a key regulator of vocal response timing. Based on a spiking network model informed by behavioral and electrophysiological data from communicating zebra finches, we predicted that two different patterns of inhibition regulate vocal-motor responses. In one scenario, the strength of production-related premotor inhibition translates into plasticity in vocal response delays. In the other scenario, fast transient interneuron activity in response to auditory input results in the suppression of call production while a call is heard, thereby reducing acoustic overlap between callers. Extracellular recordings in HVC during the listening phase confirm the presence of auditory-evoked response patterns in putative inhibitory interneurons, along with corresponding signatures of auditory-evoked activity suppression. The proposed model provides a parsimonious framework to explain how auditory-vocal transformations can give rise to vocal turn-taking and highlights multiple roles of local inhibition for behavioral modulation at different time scales.

Vocal turn-taking is a fundamental organizing principle of human conversation but the neural circuit mechanisms that structure coordinated vocal interactions are unknown. The ability to exchange vocalizations in an alternating fashion is also exhibited by other species, including zebra finches. With a combination of behavioral testing, electrophysiological recordings, and pharmacological manipulations we demonstrate that activity within a cortical premotor nucleus orchestrates the timing of calls in socially interacting zebra finches. Within this circuit, local inhibition precedes premotor neuron activation associated with calling. Blocking inhibition results in faster vocal responses as well as an impaired ability to flexibly avoid overlapping with a partner. These results support a working model in which premotor inhibition regulates context-dependent timing of vocalizations and enables the precise interleaving of vocal signals during turn-taking.