Temporal Coherence Shapes Cortical Responses to Speech Mixtures in a Ferret Cocktail Party.

Segregation of complex sounds such as speech, music and animal vocalizations as they simultaneously emanate from multiple sources (referred to as the "cocktail party problem") is a remarkable ability that is common in humans and animals alike. The neural underpinnings of this process have been extensively studied behaviorally and physiologically in non-human animals primarily with simplified sounds (tones and noise sequences). In humans, segregation experiments utilizing more complex speech mixtures are common; but physiological experiments have relied on EEG/MEG/ECoG recordings that sample activity from thousands of neurons, often obscuring the detailed processes that give rise to the observed segregation. The present study combines the insights from animal single-unit physiology with segregation of speech-like mixtures. Ferrets were trained to attend to a female voice and detect a target word, both in presence or absence of a concurrent, equally salient male voice. Single neuron recordings were obtained from primary and secondary ferret auditory cortical fields, as well as frontal cortex. During task performance, representation of the female words became more enhanced relative to those of the (distractor) male in all cortical regions, especially in the higher auditory cortical field. Analysis of the temporal and spectral response characteristics during task performance reveals how speech segregation gradually emerges in the auditory cortex. A computational model evaluated on the same voice mixtures replicates and extends these results to different attentional targets (attention to female or male voices). These findings are consistent with the temporal coherence theory whereby attention to a target voice anchors neural activity in cortical networks hence binding together channels that are coherently temporally-modulated with the target, and ultimately forming a common auditory stream.

Spinal neuromodulation mitigates myocardial ischemia-induced sympathoexcitation by suppressing the intermediolateral nucleus hyperactivity and spinal neural synchrony.

Introduction: Myocardial ischemia disrupts the cardio-spinal neural network that controls the cardiac sympathetic preganglionic neurons, leading to sympathoexcitation and ventricular tachyarrhythmias (VTs). Spinal cord stimulation (SCS) is capable of suppressing the sympathoexcitation caused by myocardial ischemia. However, how SCS modulates the spinal neural network is not fully known. Methods: In this pre-clinical study, we investigated the impact of SCS on the spinal neural network in mitigating myocardial ischemia-induced sympathoexcitation and arrhythmogenicity. Ten Yorkshire pigs with left circumflex coronary artery (LCX) occlusion-induced chronic myocardial infarction (MI) were anesthetized and underwent laminectomy and a sternotomy at 4-5 weeks post-MI. The activation recovery interval (ARI) and dispersion of repolarization (DOR) were analyzed to evaluate the extent of sympathoexcitation and arrhythmogenicity during the left anterior descending coronary artery (LAD) ischemia. Extracellular in vivo and in situ spinal dorsal horn (DH) and intermediolateral column (IML) neural recordings were performed using a multichannel microelectrode array inserted at the T2-T3 segment of the spinal cord. SCS was performed for 30 min at 1 kHz, 0.03 ms, 90% motor threshold. LAD ischemia was induced pre- and 1 min post-SCS to investigate how SCS modulates spinal neural network processing of myocardial ischemia. DH and IML neural interactions, including neuronal synchrony as well as cardiac sympathoexcitation and arrhythmogenicity markers were evaluated during myocardial ischemia pre- vs. post-SCS. Results: ARI shortening in the ischemic region and global DOR augmentation due to LAD ischemia was mitigated by SCS. Neural firing response of ischemia-sensitive neurons during LAD ischemia and reperfusion was blunted by SCS. Further, SCS showed a similar effect in suppressing the firing response of IML and DH neurons during LAD ischemia. SCS exhibited a similar suppressive impact on the mechanical, nociceptive and multimodal ischemia sensitive neurons. The LAD ischemia and reperfusion-induced augmentation in neuronal synchrony between DH-DH and DH-IML pairs of neurons were mitigated by the SCS. Discussion: These results suggest that SCS is decreasing the sympathoexcitation and arrhythmogenicity by suppressing the interactions between the spinal DH and IML neurons and activity of IML preganglionic sympathetic neurons.

Breaking barriers and building bridges: Increasing community engagement in program evaluation.

BACKGROUND: Between September 2015 and 2018, The Michigan Department of Health and Human Services (MDHHS) focused its Project PrIDE efforts on increasing PrEP awareness through a media campaign, and community engagement in. Wayne County, MI. A strained relationship between MDHHS and community has created barriers to sustained and effective community engagement. The local evaluation (LE) was developed to determine the barriers and facilitators to engagement in program activities. METHODS: To understand the process and the factors that impacted the project's goal, a mixed methods participatory evaluation approach was utilized. Data collection included quantitative data from meeting surveys, qualitative data from focus groups, and a photovoice project. Analysis and synthesis included descriptive statistics and deductive thematic coding. RESULTS: CAB engagement increased collaboration, enhanced feasibility and utility, appropriateness, sustainability of activities, and increased transparency between MDHHS and CAB. Thematic coding identified Barriers and facilitators to engagement with PrEP activites included restrictive funding, comprehensive services delivery and CAB feedback underutilized and resulting in ineffective campaign messages. CONCLUSIONS: Although a strained relationship was evident in the beginning, encouraging interagency collaboration in the development, implementation, and utilization of program and evaluation activities, resulted in the improvement of relationships between the community and MDHHS.

Is the MSB hypothesis (music as a coevolved system for social bonding) testable in the Popperian sense?

"Music As a Coevolved System for Social Bonding" (MSB) is a brilliant synthesis and appealing hypothesis offering insights into the evolution and social bonding of musicality, but is so broad and sweeping it will be challenging to test, prove or falsify in the Popperian sense (Popper, 1959). After general comments, I focus my critique on underlying neurobiological mechanisms, and offer some suggestions for experimental tests of MSB.

Changes in membrane elasticity caused by the hydrophobic surfactant proteins correlate poorly with adsorption of lipid vesicles.

To establish how the hydrophobic surfactant proteins, SP-B and SP-C, promote adsorption of lipids to an air/water interface, we used X-ray diffuse scattering (XDS) to determine an order parameter of the lipid chains (Sxray) and the bending modulus of the lipid bilayers (KC). Samples contained different amounts of the proteins with two sets of lipids. Dioleoylphosphatidylcholine (DOPC) provided a simple, well characterized model system. The nonpolar and phospholipids (N&PL) from extracted calf surfactant provided the biological mix of lipids. For both systems, the proteins produced changes in Sxray that correlated well with KC. The dose-response to the proteins, however, differed. Small amounts of protein generated large decreases in Sxray and KC for DOPC that progressed monotonically. The changes for the surfactant lipids were erratic. Our studies then tested whether the proteins produced correlated effects on adsorption. Experiments measured the initial fall in surface tension during adsorption to a constant surface area, and then expansion of the interface during adsorption at a constant surface tension of 40 mN m-1. The proteins produced a sigmoidal increase in the rate of adsorption at 40 mN m-1 for both lipids. The results correlated poorly with the changes in Sxray and KC in both cases. Disordering of the lipid chains produced by the proteins, and the softening of the bilayers, fail to explain how the proteins promote adsorption of lipid vesicles.

Suppression of Lα/Lß Phase Coexistence in the Lipids of Pulmonary Surfactant.

To determine how different constituents of pulmonary surfactant affect its phase behavior, we measured wide-angle x-ray scattering (WAXS) from oriented bilayers. Samples contained the nonpolar and phospholipids (N&PL) obtained from calf lung surfactant extract (CLSE), which also contains the hydrophobic surfactant proteins SP-B and SP-C. Mixtures with different ratios of N&PL and CLSE provided the same set of lipids with different amounts of the proteins. At 37°C, N&PL by itself forms coexisting Lα and Lß phases. In the Lß structure, the acyl chains of the phospholipids occupy an ordered array that has melted by 40°C. This behavior suggests that the Lß composition is dominated by dipalmitoyl phosphatidylcholine (DPPC), which is the most prevalent component of CLSE. The Lß chains, however, lack the tilt of the Lß' phase formed by pure DPPC. At 40°C, WAXS also detects an additional diffracted intensity, the location of which suggests a correlation among the phospholipid headgroups. The mixed samples of N&PL with CLSE show that increasing amounts of the proteins disrupt both the Lß phase and the headgroup correlation. With physiological levels of the proteins in CLSE, both types of order are absent. These results with bilayers at physiological temperatures indicate that the hydrophobic surfactant proteins disrupt the ordered structures that have long been considered essential for the ability of pulmonary surfactant to sustain low surface tensions. They agree with prior fluorescence micrographic results from monomolecular films of CLSE, suggesting that at physiological temperatures, any ordered phase is likely to be absent or occupy a minimal interfacial area.

Location of the Hydrophobic Surfactant Proteins, SP-B and SP-C, in Fluid-Phase Bilayers.

The hydrophobic surfactant proteins, SP-B and SP-C, promote rapid adsorption by the surfactant lipids to the surface of the liquid that lines the alveolar air sacks of the lungs. To gain insights into the mechanisms of their function, we used X-ray diffuse scattering (XDS) and molecular dynamics (MD) simulations to determine the location of SP-B and SP-C within phospholipid bilayers. Initial samples contained the surfactant lipids from extracted calf surfactant with increasing doses of the proteins. XDS located protein density near the phospholipid headgroup and in the hydrocarbon core, presumed to be SP-B and SP-C, respectively. Measurements on dioleoylphosphatidylcholine (DOPC) with the proteins produced similar results. MD simulations of the proteins with DOPC provided molecular detail and allowed direct comparison of the experimental and simulated results. Simulations used conformations of SP-B based on other members of the saposin-like family, which form either open or closed V-shaped structures. For SP-C, the amino acid sequence suggests a partial α-helix. Simulations fit best with measurements of XDS for closed SP-B, which occurred at the membrane surface, and SP-C oriented along the hydrophobic interior. Our results provide the most definitive evidence yet concerning the location and orientation of the hydrophobic surfactant proteins.

Dorsal prefrontal and premotor cortex of the ferret as defined by distinctive patterns of thalamo-cortical projections.

Recent studies of the neurobiology of the dorsal frontal cortex (FC) of the ferret have illuminated its key role in the attention network, top-down cognitive control of sensory processing, and goal directed behavior. To elucidate the neuroanatomical regions of the dorsal FC, and delineate the boundary between premotor cortex (PMC) and dorsal prefrontal cortex (dPFC), we placed retrograde tracers in adult ferret dorsal FC anterior to primary motor cortex and analyzed thalamo-cortical connectivity. Cyto- and myeloarchitectural differences across dorsal FC and the distinctive projection patterns from thalamic nuclei, especially from the subnuclei of the medial dorsal (MD) nucleus and the ventral thalamic nuclear group, make it possible to clearly differentiate three separate dorsal FC fields anterior to primary motor cortex: polar dPFC (dPFCpol), dPFC, and PMC. Based on the thalamic connectivity, there is a striking similarity of the ferret's dorsal FC fields with other species. This possible homology opens up new questions for future comparative neuroanatomical and functional studies.

Dynamics and Hierarchical Encoding of Non-compact Acoustic Categories in Auditory and Frontal Cortex.

Categorical perception is a fundamental cognitive function enabling animals to flexibly assign sounds into behaviorally relevant categories. This study investigates the nature of acoustic category representations, their emergence in an ascending series of ferret auditory and frontal cortical fields, and the dynamics of this representation during passive listening to task-relevant stimuli and during active retrieval from memory while engaging in learned categorization tasks. Ferrets were trained on two auditory Go-NoGo categorization tasks to discriminate two non-compact sound categories (composed of tones or amplitude-modulated noise). Neuronal responses became progressively more categorical in higher cortical fields, especially during task performance. The dynamics of the categorical responses exhibited a cascading top-down modulation pattern that began earliest in the frontal cortex and subsequently flowed downstream to the secondary auditory cortex, followed by the primary auditory cortex. In a subpopulation of neurons, categorical responses persisted even during the passive listening condition, demonstrating memory for task categories and their enhanced categorical boundaries.

What can animal communication teach us about human language?

Language has been considered by many to be uniquely human. Numerous theories for how it evolved have been proposed but rarely tested. The articles in this theme issue consider the extent to which aspects of language, such as vocal learning, phonology, syntax, semantics, intentionality, cognition and neurobiological adaptations, are shared with other animals. By adopting a comparative approach, insights into the mechanisms and origins of human language can be gained. While points of agreement exist among the authors, conflicting viewpoints are expressed on several issues, such as the presence of proto-syntax in animal communication, the neural basis of the Merge operation, and the neurogenetic changes necessary for vocal learning. Future comparative research in animal communication has the potential to teach us even more about the evolution, neurobiology and cognitive basis of human language. This article is part of the theme issue 'What can animal communication teach us about human language?'

Adaptive Efficient Coding of Correlated Acoustic Properties.

Natural sounds such as vocalizations often have covarying acoustic attributes, resulting in redundancy in neural coding. The efficient coding hypothesis proposes that sensory systems are able to detect such covariation and adapt to reduce redundancy, leading to more efficient neural coding. Recent psychoacoustic studies have shown the auditory system can rapidly adapt to efficiently encode two covarying dimensions as a single dimension, following passive exposure to sounds in which temporal and spectral attributes covaried in a correlated fashion. However, these studies observed a cost to this adaptation, which was a loss of sensitivity to the orthogonal dimension. Here we explore the neural basis of this psychophysical phenomenon by recording single-unit responses from the primary auditory cortex in awake ferrets exposed passively to stimuli with two correlated attributes, similar in stimulus design to the psychoacoustic experiments in humans. We found: (1) the signal-to-noise ratio of spike-rate coding of cortical responses driven by sounds with correlated attributes remained unchanged along the exposure dimension, but was reduced along the orthogonal dimension; (2) performance of a decoder trained with spike data to discriminate stimuli along the orthogonal dimension was equally reduced; (3) correlations between neurons tuned to the two covarying attributes decreased after exposure; and (4) these exposure effects still occurred if sounds were correlated along two acoustic dimensions, but varied randomly along a third dimension. These neurophysiological results are consistent with the efficient coding hypothesis and may help deepen our understanding of how the auditory system encodes and represents acoustic regularities and covariance.SIGNIFICANCE STATEMENT The efficient coding (EC) hypothesis (Attneave, 1954; Barlow, 1961) proposes that the neural code in sensory systems efficiently encodes natural stimuli by minimizing the number of spikes to transmit a sensory signal. Results of recent psychoacoustic studies in humans are consistent with the EC hypothesis in that, following passive exposure to stimuli with correlated attributes, the auditory system rapidly adapts so as to more efficiently encode the two covarying dimensions as a single dimension. In the current neurophysiological experiments, using a similar stimulus design and the experimental paradigm to the psychoacoustic studies of Stilp et al. (2010) and Stilp and Kluender (2011, 2012, 2016), we recorded responses from single neurons in the auditory cortex of the awake ferret, showing adaptive efficient neural coding of two correlated acoustic attributes.

C-H Borylation Catalysts that Distinguish Between Similarly Sized Substituents Like Fluorine and Hydrogen.

By modifying ligand steric and electronic profiles it is possible to C-H borylate ortho or meta to substituents in aromatic and heteroaromatic compounds, where steric differences between accessible C-H sites are small. Dramatic effects on selectivities between reactions using B2pin2 or 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (HBpin) are described for the first time. Judicious ligand and borane combinations give highly regioselective C-H borylations on substrates where typical borylation protocols afford poor selectivities.

Computational Neural Modeling of Auditory Cortical Receptive Fields.

Previous studies have shown that the auditory cortex can enhance the perception of behaviorally important sounds in the presence of background noise, but the mechanisms by which it does this are not yet elucidated. Rapid plasticity of spectrotemporal receptive fields (STRFs) in the primary (A1) cortical neurons is observed during behavioral tasks that require discrimination of particular sounds. This rapid task-related change is believed to be one of the processing strategies utilized by the auditory cortex to selectively attend to one stream of sound in the presence of mixed sounds. However, the mechanism by which the brain evokes this rapid plasticity in the auditory cortex remains unclear. This paper uses a neural network model to investigate how synaptic transmission within the cortical neuron network can change the receptive fields of individual neurons. A sound signal was used as input to a model of the cochlea and auditory periphery, which activated or inhibited integrate-and-fire neuron models to represent networks in the primary auditory cortex. Each neuron in the network was tuned to a different frequency. All neurons were interconnected with excitatory or inhibitory synapses of varying strengths. Action potentials in one of the model neurons were used to calculate the receptive field using reverse correlation. The results were directly compared to previously recorded electrophysiological data from ferrets performing behavioral tasks that require discrimination of particular sounds. The neural network model could reproduce complex STRFs observed experimentally through optimizing the synaptic weights in the model. The model predicts that altering synaptic drive between cortical neurons and/or bottom-up synaptic drive from the cochlear model to the cortical neurons can account for rapid task-related changes observed experimentally in A1 neurons. By identifying changes in the synaptic drive during behavioral tasks, the model provides insights into the neural mechanisms utilized by the auditory cortex to enhance the perception of behaviorally salient sounds.

State-dependent encoding of sound and behavioral meaning in a tertiary region of the ferret auditory cortex.

In higher sensory cortices, there is a gradual transformation from sensation to perception and action. In the auditory system, this transformation is revealed by responses in the rostral ventral posterior auditory field (VPr), a tertiary area in the ferret auditory cortex, which shows long-term learning in trained compared to naïve animals, arising from selectively enhanced responses to behaviorally relevant target stimuli. This enhanced representation is further amplified during active performance of spectral or temporal auditory discrimination tasks. VPr also shows sustained short-term memory activity after target stimulus offset, correlated with task response timing and action. These task-related changes in auditory filter properties enable VPr neurons to quickly and nimbly switch between different responses to the same acoustic stimuli, reflecting either spectrotemporal properties, timing, or behavioral meaning of the sound. Furthermore, they demonstrate an interaction between the dynamics of short-term attention and long-term learning, as incoming sound is selectively attended, recognized, and translated into action.

Getting pre-exposure prophylaxis to high-risk transgender women: lessons from Detroit, USA.

Background Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention strategy, but it is unclear how best to deliver PrEP to key populations. Drawing upon a cross-sectional survey of transgender women (TW) in Detroit, USA, and experience of a PrEP clinic that serves this population, this manuscript describes the following: (1) the risk profile of Detroit TW; (2) the proportion of TW with at least one PrEP indication; and (3) perceptions of and experiences with PrEP among TW in Detroit. METHODS: Between August 2017 and March 2018, 126 TW completed an online PrEP survey. Survey responses were summarised using descriptive statistics and multivariable relative risk regression. RESULTS: Among participants who reported a negative or unknown HIV status (76% of all participants), 56% reported risk behaviour(s) consistent with PrEP indication guidelines, 17% reported currently taking PrEP and another 4% reported discontinued PrEP use. Among participants who met an indication for PrEP but were not currently taking PrEP, 64% indicated that they were not interested in taking PrEP. Approximately 60% of participants who were not currently taking PrEP reported that they would be more likely to take PrEP if it were provided at a clinic that also provided hormone replacement therapy. CONCLUSIONS: Although a substantial proportion of TW in our survey were on PrEP, interest in PrEP among high-risk TW who were not taking it was low. Specialised clinical infrastructure that is responsive to the specific needs of TW may be needed to expand PrEP to this oftentimes marginalised and high-risk population.

Laminar profile of task-related plasticity in ferret primary auditory cortex.

Rapid task-related plasticity is a neural correlate of selective attention in primary auditory cortex (A1). Top-down feedback from higher-order cortex may drive task-related plasticity in A1, characterized by enhanced neural representation of behaviorally meaningful sounds during auditory task performance. Since intracortical connectivity is greater within A1 layers 2/3 (L2/3) than in layers 4-6 (L4-6), we hypothesized that enhanced representation of behaviorally meaningful sounds might be greater in A1 L2/3 than L4-6. To test this hypothesis and study the laminar profile of task-related plasticity, we trained 2 ferrets to detect pure tones while we recorded laminar activity across a 1.8 mm depth in A1. In each experiment we analyzed high-gamma local field potentials (LFPs) and multi-unit spiking in response to identical acoustic stimuli during both passive listening and active task performance. We found that neural responses to auditory targets were enhanced during task performance, and target enhancement was greater in L2/3 than in L4-6. Spectrotemporal receptive fields (STRFs) computed from both high-gamma LFPs and multi-unit spiking showed similar increases in auditory target selectivity, also greatest in L2/3. Our results suggest that activity within intracortical networks plays a key role in the underlying neural mechanisms of selective attention.

Implicit Memory for Complex Sounds in Higher Auditory Cortex of the Ferret.

Responses of auditory cortical neurons encode sound features of incoming acoustic stimuli and also are shaped by stimulus context and history. Previous studies of mammalian auditory cortex have reported a variable time course for such contextual effects ranging from milliseconds to minutes. However, in secondary auditory forebrain areas of songbirds, long-term stimulus-specific neuronal habituation to acoustic stimuli can persist for much longer periods of time, ranging from hours to days. Such long-term habituation in the songbird is a form of long-term auditory memory that requires gene expression. Although such long-term habituation has been demonstrated in avian auditory forebrain, this phenomenon has not previously been described in the mammalian auditory system. Utilizing a similar version of the avian habituation paradigm, we explored whether such long-term effects of stimulus history also occur in auditory cortex of a mammalian auditory generalist, the ferret. Following repetitive presentation of novel complex sounds, we observed significant response habituation in secondary auditory cortex, but not in primary auditory cortex. This long-term habituation appeared to be independent for each novel stimulus and often lasted for at least 20 min. These effects could not be explained by simple neuronal fatigue in the auditory pathway, because time-reversed sounds induced undiminished responses similar to those elicited by completely novel sounds. A parallel set of pupillometric response measurements in the ferret revealed long-term habituation effects similar to observed long-term neural habituation, supporting the hypothesis that habituation to passively presented stimuli is correlated with implicit learning and long-term recognition of familiar sounds.SIGNIFICANCE STATEMENT Long-term habituation in higher areas of songbird auditory forebrain is associated with gene expression and is correlated with recognition memory. Similar long-term auditory habituation in mammals has not been previously described. We studied such habituation in single neurons in the auditory cortex of awake ferrets that were passively listening to repeated presentations of various complex sounds. Responses exhibited long-lasting habituation (at least 20 min) in the secondary, but not primary auditory cortex. Habituation ceased when stimuli were played backward, despite having identical spectral content to the original sound. This long-term neural habituation correlated with similar habituation of ferret pupillary responses to repeated presentations of the same stimuli, suggesting that stimulus habituation is retained as a long-term behavioral memory.

Go/No-Go task engagement enhances population representation of target stimuli in primary auditory cortex.

Primary sensory cortices are classically considered to extract and represent stimulus features, while association and higher-order areas are thought to carry information about stimulus meaning. Here we show that this information can in fact be found in the neuronal population code of the primary auditory cortex (A1). A1 activity was recorded in awake ferrets while they either passively listened or actively discriminated stimuli in a range of Go/No-Go paradigms, with different sounds and reinforcements. Population-level dimensionality reduction techniques reveal that task engagement induces a shift in stimulus encoding from a sensory to a behaviorally driven representation that specifically enhances the target stimulus in all paradigms. This shift partly relies on task-engagement-induced changes in spontaneous activity. Altogether, we show that A1 population activity bears strong similarities to frontal cortex responses. These findings indicate that primary sensory cortices implement a crucial change in the structure of population activity to extract task-relevant information during behavior.

Extracting neuronal functional network dynamics via adaptive Granger causality analysis.

Quantifying the functional relations between the nodes in a network based on local observations is a key challenge in studying complex systems. Most existing time series analysis techniques for this purpose provide static estimates of the network properties, pertain to stationary Gaussian data, or do not take into account the ubiquitous sparsity in the underlying functional networks. When applied to spike recordings from neuronal ensembles undergoing rapid task-dependent dynamics, they thus hinder a precise statistical characterization of the dynamic neuronal functional networks underlying adaptive behavior. We develop a dynamic estimation and inference paradigm for extracting functional neuronal network dynamics in the sense of Granger, by integrating techniques from adaptive filtering, compressed sensing, point process theory, and high-dimensional statistics. We demonstrate the utility of our proposed paradigm through theoretical analysis, algorithm development, and application to synthetic and real data. Application of our techniques to two-photon Ca2+ imaging experiments from the mouse auditory cortex reveals unique features of the functional neuronal network structures underlying spontaneous activity at unprecedented spatiotemporal resolution. Our analysis of simultaneous recordings from the ferret auditory and prefrontal cortical areas suggests evidence for the role of rapid top-down and bottom-up functional dynamics across these areas involved in robust attentive behavior.

Orbitofrontal Cortex Neurons Respond to Sound and Activate Primary Auditory Cortex Neurons.

Sensory environments change over a wide dynamic range and sensory processing can change rapidly to facilitate stable perception. While rapid changes may occur throughout the sensory processing pathway, cortical changes are believed to profoundly influence perception. Prior stimulation studies showed that orbitofrontal cortex (OFC) can modify receptive fields and sensory coding in A1, but the engagement of OFC during listening and the pathways mediating OFC influences on A1 are unknown. We show in mice that OFC neurons respond to sounds consistent with a role of OFC in audition. We then show in vitro that OFC axons are present in A1 and excite pyramidal and GABAergic cells in all layers of A1 via glutamatergic synapses. Optogenetic stimulation of OFC terminals in A1 in vivo evokes short-latency neural activity in A1 and pairing activation of OFC projections in A1 with sounds alters sound-evoked A1 responses. Together, our results identify a direct connection from OFC to A1 that can excite A1 neurons at the earliest stage of cortical processing, and thereby sculpt A1 receptive fields. These results are consistent with a role for OFC in adjusting to changing behavioral relevance of sensory inputs and modulating A1 receptive fields to enhance sound processing.