The role of auditory feedback in vocal learning and maintenance

Auditory experience is critical for the acquisition and maintenance of learned vocalizations in both humans and songbirds. Despite the central role of auditory feedback in vocal learning and maintenance, where and how auditory feedback affects neural circuits important to vocal control remain poorly understood. Recent studies of singing birds have uncovered neural mechanisms by which feedback perturbations affect vocal plasticity and also have identified feedback-sensitive neurons at or near sites of auditory and vocal motor interaction. Additionally, recent studies in marmosets have underscored that even in the absence of vocal learning, vocalization remains flexible in the face of changing acoustical environments, pointing to rapid interactions between auditory and vocal motor systems. Finally, recent studies show that a juvenile songbird's initial auditory experience of a song model has long-lasting effects on sensorimotor neurons important to vocalization, shedding light on how auditory memories and feedback interact to guide vocal learning.     

LMAN lesions prevent song degradation after deafening without reducing HVC neuron addition

In some songbirds perturbing auditory feedback can promote changes in song structure well beyond the end of song learning. One factor that may drive vocal change in such deafened birds is the ongoing addition of new vocal-motor neurons into the song system. Without auditory feedback to guide their incorporation, the addition of these new neurons could disrupt the established song pattern. To assess this hypothesis, the authors determined if neuronal recruitment into the vocal motor nucleus HVC is affected by neural signals that influence vocal change in adult deafened birds. Such signals appear to be conveyed via LMAN, a nucleus in the anterior forebrain that is necessary for vocal change after deafening. Here the authors tested whether LMAN lesions might restrict song degradation after deafening by reducing the addition or survival of new HVC neurons that would otherwise corrupt the ongoing song pattern. Using [3H]thymidine autoradiography to identify neurons generated in adult zebra finches, it was shown here that LMAN lesions do not reduce the number or percent of new HVC neurons surviving for either several weeks or months after [3H]thymidine labeling. However, the authors confirmed previous reports that LMAN lesions restrict vocal change after deafening. These data suggest that neurons incorporated into the adult HVC may form behaviorally adaptive connections without requiring auditory feedback, and that any role such neurons may play in promoting vocal change after adult deafening requires anterior forebrain pathway output.     

Of Mice,Birds, and Men: The Mouse Ultrasonic Song System Has Some Features Similar to Humans and Song-Learning Birds

Humans and song-learning birds communicate acoustically using learned vocalizations. The characteristic features of this social communication behavior include vocal control by forebrain motor areas, a direct cortical projection to brainstem vocal motor neurons, and dependence on auditory feedback to develop and maintain learned vocalizations. These features have so far not been found in closely related primate and avian species that do not learn vocalizations. Male mice produce courtship ultrasonic vocalizations with acoustic features similar to songs of song-learning birds. However, it is assumed that mice lack a forebrain system for vocal modification and that their ultrasonic vocalizations are innate. Here we investigated the mouse song system and discovered that it includes a motor cortex region active during singing, that projects directly to brainstem vocal motor neurons and is necessary for keeping song more stereotyped and on pitch. We also discovered that male mice depend on auditory feedback to maintain some ultrasonic song features, and that sub-strains with differences in their songs can match each other''s pitch when cross-housed under competitive social conditions. We conclude that male mice have some limited vocal modification abilities with at least some neuroanatomical features thought to be unique to humans and song-learning birds. To explain our findings, we propose a continuum hypothesis of vocal learning.     

Neuron loss and addition in developing zebra finch song nuclei are independent of auditory experience during song learning

In zebra finches early auditory experience is critical for normal song development. Young males first listen to and memorize a suitable song model and then use auditory feedback from their own vocalizations to mimic that model. During these two phases of vocal learning, song-related brain regions exhibit large, hormone-induced changes in volume and neuron number. Overlap between these neural changes and auditory-based vocal learning suggests that processing and acquiring auditory input may influence cellular processes that determine neuron number in the song system. We addressed this hypothesis by measuring neuron density, nuclear volume, and neuron number within the song system of normal male zebra finches and males deafened prior to song learning (10 days of age). Measures were obtained at 25, 50, 65, and 120 days of age, and included four song nuclei: the hyperstriatum ventralis pars caudalis or higher vocal center (HVc), Area X, the robust nucleus of the archistriatum (RA), and the lateral magnocellular nucleus of the anterior neostriatum (IMAN). In both HVc and Area X, nuclear volume and neuron number increased markedly with age in both normal and deafened birds. The volume of RA also increased with age and was not affected by early deafening. In IMAN, deafening also did not affect the overall age-related loss of neurons, although at 25 days neuron number was slightly less in deafened than in normal birds. We conclude that while the addition and loss of neurons in the developing song system may provide plasticity essential for song learning, these changes do not reflect learning.(ABSTRACT TRUNCATED AT 250 WORDS)     

A sensorimotor area in the songbird brain is required for production of vocalizations in the song learning period of development

Sensory feedback is essential for acquiring and maintaining complex motor behaviors, including birdsong. In zebra finches, auditory feedback reaches the song control circuits primarily through the nucleus interfacialis nidopalii (Nif), which provides excitatory input to HVC (proper name)—a premotor region essential for the production of learned vocalizations. Despite being one of the major inputs to the song control pathway, the role of Nif in generating vocalizations is not well understood. To address this, we transiently inactivated Nif in late juvenile zebra finches. Upon Nif inactivation (in both hemispheres or on one side only), birds went from singing stereotyped zebra finch song to uttering highly variable and unstructured vocalizations resembling sub‐song, an early juvenile song form driven by a basal ganglia circuit. Simultaneously inactivating Nif and LMAN (lateral magnocellular nucleus of the anterior nidopallium), the output nucleus of a basal ganglia circuit, inhibited song production altogether. These results suggest that Nif is required for generating the premotor drive for song. Permanent Nif lesions, in contrast, have only transient effects on vocal production, with song recovering within a day. The sensorimotor nucleus Nif thus produces a premotor drive to the motor pathway that is acutely required for generating learned vocalizations, but once permanently removed, the song system can compensate for its absence. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1213–1225, 2016     

An Adapting Auditory-motor Feedback Loop Can Contribute to Generating Vocal Repetition

Consecutive repetition of actions is common in behavioral sequences. Although integration of sensory feedback with internal motor programs is important for sequence generation, if and how feedback contributes to repetitive actions is poorly understood. Here we study how auditory feedback contributes to generating repetitive syllable sequences in songbirds. We propose that auditory signals provide positive feedback to ongoing motor commands, but this influence decays as feedback weakens from response adaptation during syllable repetitions. Computational models show that this mechanism explains repeat distributions observed in Bengalese finch song. We experimentally confirmed two predictions of this mechanism in Bengalese finches: removal of auditory feedback by deafening reduces syllable repetitions; and neural responses to auditory playback of repeated syllable sequences gradually adapt in sensory-motor nucleus HVC. Together, our results implicate a positive auditory-feedback loop with adaptation in generating repetitive vocalizations, and suggest sensory adaptation is important for feedback control of motor sequences.     

Songbird: a unique animal model for studying the molecular basis of disorders of vocal development and communication

Like humans, songbirds are one of the few animal groups that learn vocalization. Vocal learning requires coordination of auditory input and vocal output using auditory feedback to guide one’s own vocalizations during a specific developmental stage known as the critical period. Songbirds are good animal models for understand the neural basis of vocal learning, a complex form of imitation, because they have many parallels to humans with regard to the features of vocal behavior and neural circuits dedicated to vocal learning. In this review, we will summarize the behavioral, neural, and genetic traits of birdsong. We will also discuss how studies of birdsong can help us understand how the development of neural circuits for vocal learning and production is driven by sensory input (auditory information) and motor output (vocalization).     

A bird's eye view: top down intracellular analyses of auditory selectivity for learned vocalizations

The "song system" refers to a group of interconnected brain nuclei necessary for the utterance of learned song and for the generation of vocal plasticity important to both song learning and adult song maintenance. Although song learning and, in some species, song maintenance depend on auditory feedback, how audition influences vocalization remains unknown. One attractive idea is that auditory signals propagate directly to those telencephalic nuclei implicated in song patterning, providing a convenient substrate for sensorimotor integration. Consistent with this idea, auditory neurons highly selective for the bird's own song have been detected in telencephalic song nuclei, and lesions of these structures can impair song perception as well as song production. This review discusses evidence for an auditory-perceptual role of the song system, the anatomical pathways by which auditory information enters the song system, the synaptic events underlying highly selective action potential responses to learned song, and the possible roles such activity could play in song learning and maintenance.     

The relationship between rates of HVc neuron addition and vocal plasticity in adult songbirds

In adulthood, songbird species vary considerably in the extent to which they rely on auditory feedback to maintain a stable song structure. The continued recruitment of new neurons into vocal motor circuitry may contribute to this lack of resiliency in song behavior insofar as new neurons that are not privy to auditory instruction could eventually corrupt established neural function. In a first step to explore this possibility, we used a comparative approach to determine if species differences in the rate of vocal change after deafening in adulthood correlate positively with the extent of HVc neuron addition. We confirmed previous reports that deafening in adulthood changes syllable phonology much more rapidly in bengalese finches than in zebra finches. Using [(3)H]thymidine autoradiography to identify neurons generated in adulthood, we found that the proportion of new neurons in the HVc one month after labeling was nearly twice as great in bengalese than in zebra finches. Moreover, among the subset of HVc vocal motor neurons that project to the robust nucleus of the archistriatum, the incidence of [(3)H]thymidine-labeled neurons was nearly three times as great in bengalese than in zebra finches. This correlation between the proportion of newly added neurons and the rate of song deterioration supports the hypothesis that HVc neuron addition may disrupt stable adult song production if new neurons cannot be "trained" via auditory feedback.     

Auditory processing of vocal sounds in birds

The avian auditory system has become a model system to investigate how vocalizations are memorized and processed by the brain in order to mediate behavioral discrimination and recognition. Recent studies have shown that most of the avian auditory system responds preferentially and efficiently to sounds that have natural spectro-temporal statistics. In addition, neurons in secondary auditory forebrain areas have plastic response properties and are the most active when processing behaviorally relevant vocalizations. Physiological measurements show differential responses for vocalizations that were recently learned in discrimination tasks, and for the tutor song, a longer-term auditory memory that is used to guide vocal learning in male songbirds.     

Birdsong: From behaviour to brain

Although vocal communication is wide-spread in animal kingdom, the use of learned (in contrast to innate) vocalization is very rare. We can find it only in few animal taxa: human, bats, whales and dolphins, elephants, parrots, hummingbirds, and songbirds. There are several parallels between human and songbird perception and production of vocal signals. Hence, many studies take interest in songbird singing for investigating the neural bases of learning and memory. Brain circuits controlling song learning and maintenance consist of two pathways — a vocal motor pathway responsible for production of learned vocalizations and anterior forebrain pathway responsible for learning and modifying the vocalizations. This review provides an overview of the song organization, its behavioural traits, and neural regulations. The recently expanding area of molecular mapping of the behaviour-driven gene expression in brain represents one of the modern approaches to the study the function of vocal and auditory areas for song learning and maintenance in birds.     

Variable Food Begging Calls Are Harbingers of Vocal Learning

Vocal learning has evolved in only a few groups of mammals and birds. The developmental and evolutionary origins of vocal learning remain unclear. The imitation of a memorized sound is a clear example of vocal learning, but is that when vocal learning starts? Here we use an ontogenetic approach to examine how vocal learning emerges in a songbird, the chipping sparrow. The first vocalizations of songbirds, food begging calls, were thought to be innate, and vocal learning emerges later during subsong, a behavior reminiscent of infant babbling. Here we report that the food begging calls of male sparrows show several characteristics associated with learned song: male begging calls are highly variable between individuals and are altered by deafening; the production of food begging calls induces c-fos expression in a forebrain motor nucleus, RA, that is involved with the production of learned song. Electrolytic lesions of RA significantly reduce the variability of male calls. The male begging calls are subsequently incorporated into subsong, which in turn transitions into recognizable attempts at vocal imitation. Females do not sing and their begging calls are not affected by deafening or RA lesion. Our results suggest that, in chipping sparrows, intact hearing can influence the quality of male begging calls, auditory-sensitive vocal variability during food begging calls is the first step in a modification of vocal output that eventually culminates with vocal imitation.     

Auditory–vocal mirroring in songbirds

Mirror neurons are theorized to serve as a neural substrate for spoken language in humans, but the existence and functions of auditory–vocal mirror neurons in the human brain remain largely matters of speculation. Songbirds resemble humans in their capacity for vocal learning and depend on their learned songs to facilitate courtship and individual recognition. Recent neurophysiological studies have detected putative auditory–vocal mirror neurons in a sensorimotor region of the songbird''s brain that plays an important role in expressive and receptive aspects of vocal communication. This review discusses the auditory and motor-related properties of these cells, considers their potential role on song learning and communication in relation to classical studies of birdsong, and points to the circuit and developmental mechanisms that may give rise to auditory–vocal mirroring in the songbird''s brain.     

Noradrenergic control of gene expression and long-term neuronal adaptation evoked by learned vocalizations in songbirds

Norepinephrine (NE) is thought to play important roles in the consolidation and retrieval of long-term memories, but its role in the processing and memorization of complex acoustic signals used for vocal communication has yet to be determined. We have used a combination of gene expression analysis, electrophysiological recordings and pharmacological manipulations in zebra finches to examine the role of noradrenergic transmission in the brain's response to birdsong, a learned vocal behavior that shares important features with human speech. We show that noradrenergic transmission is required for both the expression of activity-dependent genes and the long-term maintenance of stimulus-specific electrophysiological adaptation that are induced in central auditory neurons by stimulation with birdsong. Specifically, we show that the caudomedial nidopallium (NCM), an area directly involved in the auditory processing and memorization of birdsong, receives strong noradrenergic innervation. Song-responsive neurons in this area express α-adrenergic receptors and are in close proximity to noradrenergic terminals. We further show that local α-adrenergic antagonism interferes with song-induced gene expression, without affecting spontaneous or evoked electrophysiological activity, thus dissociating the molecular and electrophysiological responses to song. Moreover, α-adrenergic antagonism disrupts the maintenance but not the acquisition of the adapted physiological state. We suggest that the noradrenergic system regulates long-term changes in song-responsive neurons by modulating the gene expression response that is associated with the electrophysiological activation triggered by song. We also suggest that this mechanism may be an important contributor to long-term auditory memories of learned vocalizations.     

A Lightweight,Headphones-based System for Manipulating Auditory Feedback in Songbirds

Experimental manipulations of sensory feedback during complex behavior have provided valuable insights into the computations underlying motor control and sensorimotor plasticity¹. Consistent sensory perturbations result in compensatory changes in motor output, reflecting changes in feedforward motor control that reduce the experienced feedback error. By quantifying how different sensory feedback errors affect human behavior, prior studies have explored how visual signals are used to recalibrate arm movements^2,3 and auditory feedback is used to modify speech production^4-7. The strength of this approach rests on the ability to mimic naturalistic errors in behavior, allowing the experimenter to observe how experienced errors in production are used to recalibrate motor output.Songbirds provide an excellent animal model for investigating the neural basis of sensorimotor control and plasticity^8,9. The songbird brain provides a well-defined circuit in which the areas necessary for song learning are spatially separated from those required for song production, and neural recording and lesion studies have made significant advances in understanding how different brain areas contribute to vocal behavior^9-12. However, the lack of a naturalistic error-correction paradigm - in which a known acoustic parameter is perturbed by the experimenter and then corrected by the songbird - has made it difficult to understand the computations underlying vocal learning or how different elements of the neural circuit contribute to the correction of vocal errors¹³.The technique described here gives the experimenter precise control over auditory feedback errors in singing birds, allowing the introduction of arbitrary sensory errors that can be used to drive vocal learning. Online sound-processing equipment is used to introduce a known perturbation to the acoustics of song, and a miniaturized headphones apparatus is used to replace a songbird''s natural auditory feedback with the perturbed signal in real time. We have used this paradigm to perturb the fundamental frequency (pitch) of auditory feedback in adult songbirds, providing the first demonstration that adult birds maintain vocal performance using error correction¹⁴. The present protocol can be used to implement a wide range of sensory feedback perturbations (including but not limited to pitch shifts) to investigate the computational and neurophysiological basis of vocal learning.     

Development of Auditory-Vocal Perceptual Skills in Songbirds

Songbirds are one of the few groups of animals that learn the sounds used for vocal communication during development. Like humans, songbirds memorize vocal sounds based on auditory experience with vocalizations of adult “tutors”, and then use auditory feedback of self-produced vocalizations to gradually match their motor output to the memory of tutor sounds. In humans, investigations of early vocal learning have focused mainly on perceptual skills of infants, whereas studies of songbirds have focused on measures of vocal production. In order to fully exploit songbirds as a model for human speech, understand the neural basis of learned vocal behavior, and investigate links between vocal perception and production, studies of songbirds must examine both behavioral measures of perception and neural measures of discrimination during development. Here we used behavioral and electrophysiological assays of the ability of songbirds to distinguish vocal calls of varying frequencies at different stages of vocal learning. The results show that neural tuning in auditory cortex mirrors behavioral improvements in the ability to make perceptual distinctions of vocal calls as birds are engaged in vocal learning. Thus, separate measures of neural discrimination and behavioral perception yielded highly similar trends during the course of vocal development. The timing of this improvement in the ability to distinguish vocal sounds correlates with our previous work showing substantial refinement of axonal connectivity in cortico-basal ganglia pathways necessary for vocal learning.     

Learning to communicate

Of the few animal groups that learn their vocalizations, songbirds are uniquely amenable to molecular, physiological, and behavioral analyses of the neural features responsible for vocal learning. In order to communicate effectively as an adult, a young songbird recognizes and memorizes a model of his species-specific song during a developmentally critical period called sensory acquisition. Factors are now emerging that contribute to the length and strength of this learning phase. In a second critical period, known as sensorimotor learning, the young bird uses auditory feedback to perfect his motor performance, creating a match to the memorized model. New studies show that motor matching can persist beyond sensorimotor learning, and thus a role for the acquired model might also persist into adulthood. Fascinating in their own right, songbirds also provide optimism that mature brains have recourse to plasticity.     

Neural correlates of learned song in the avian forebrain: simultaneous representation of self and others

Songbirds are extraordinary vocalists and sensitive listeners, singing to communicate identity, engage other birds in acoustical combat, and attract mates. These processes involve auditory plasticity in that birds rapidly learn to discriminate novel from familiar songs. Songbirds also are one of the few non-human animals that use auditory feedback to learn their vocalizations, thus auditory -- vocal interactions are likely to be important to vocal learning. Recent advances strengthen the connection between song recognition and processing of birdsong in the auditory telencephalon. New insights also have emerged into the mechanisms underlying the 'gating' of auditory responses and the emergence of highly selective responses, two processes that could facilitate auditory feedback important to song learning.     

Children's development of self-regulation in speech production

Species-specific vocalizations fall into two broad categories: those that emerge during maturation, independent of experience, and those that depend on early life interactions with conspecifics. Human language and the communication systems of a small number of other species, including songbirds, fall into this latter class of vocal learning. Self-monitoring has been assumed to play an important role in the vocal learning of speech and studies demonstrate that perception of your own voice is crucial for both the development and lifelong maintenance of vocalizations in humans and songbirds. Experimental modifications of auditory feedback can also change vocalizations in both humans and songbirds. However, with the exception of large manipulations of timing, no study to date has ever directly examined the use of auditory feedback in speech production under the age of 4. Here we use a real-time formant perturbation task to compare the response of toddlers, children, and adults to altered feedback. Children and adults reacted to this manipulation by changing their vowels in a direction opposite to the perturbation. Surprisingly, toddlers' speech didn't change in response to altered feedback, suggesting that long-held assumptions regarding the role of self-perception in articulatory development need to be reconsidered.