Computation of interaural time difference in the owl's coincidence detector neurons.

Both the mammalian and avian auditory systems localize sound sources by computing the interaural time difference (ITD) with submillisecond accuracy. The neural circuits for this computation in birds consist of axonal delay lines and coincidence detector neurons. Here, we report the first in vivo intracellular recordings from coincidence detectors in the nucleus laminaris of barn owls. Binaural tonal stimuli induced sustained depolarizations (DC) and oscillating potentials whose waveforms reflected the stimulus. The amplitude of this sound analog potential (SAP) varied with ITD, whereas DC potentials did not. The amplitude of the SAP was correlated with firing rate in a linear fashion. Spike shape, synaptic noise, the amplitude of SAP, and responsiveness to current pulses differed between cells at different frequencies, suggesting an optimization strategy for sensing sound signals in neurons tuned to different frequencies.

From central pattern generator to sensory template in the evolution of birdsong.

Central nervous networks, be they a part of the human brain or a group of neurons in a snail, may be designed to produce distinct patterns of movement. Central pattern generators can account for the development and production of normal vocal signals without auditory feedback in non-songbirds. Songbirds need auditory feedback to develop and maintain the normal song of their species. The prerequisite for the use of auditory feedback for the control of song is a set of acoustic criteria or a template to which voice must match. The template method perhaps evolved to free birds from fixed central pattern generators, resulting in the evolution of diverse and complex songs among oscine songbirds. The evolution of human speech may have followed a similar course.

New brain pathways found in the vocal control system of a songbird.

Songbirds use a complex network of discrete brain areas and connecting fiber tracts to sing their song, but our knowledge of this circuitry may be incomplete. The forebrain area, "caudal mesopallium" (CM), has received much attention recently for its song-related activities. HVC, a prominent song system nucleus, projects to a restricted area of the CM known as the avalanche nucleus (Av). However, the other connections of Av remain unknown. Here we used tract-tracing methods to examine the connections of Av to other song system nuclei. Injections of biotinylated dextran amine (BDA) into Av labeled both afferent terminals and neurons in HVC and the interfacial nucleus of the nidopallium (NIf), suggesting that there is complex feedforward and feedback communication between these nuclei (HVC<-->Av<-->NIf). Labeled neurons were also found in the uvaeform nucleus (Uva), which was substantiated by BDA injections into Uva that labeled terminals in Av. Double fluorescent tracing experiments confirm that both HVC and Uva project to Av. The present study adds complex new connections that expand the traditional song system circuitry into the caudal mesopallium. These new pathways are likely to have broad implications for deciphering how this intricate system works.

Variability reduction in interaural time difference tuning in the barn owl.

The interaural time difference (ITD) is the primary auditory cue used by the barn owl for localization in the horizontal direction. ITD is initially computed by circuits consisting of axonal delay lines from one of the cochlear nuclei and coincidence detector neurons in the nucleus laminaris (NL). NL projects directly to the anterior part of the dorsal lateral lemniscal nucleus (LLDa), and this area projects to the core of the central nucleus of the inferior colliculus (ICcc) in the midbrain. To show the selectivity of an NL neuron for ITD requires averaging of responses over several stimulus presentations for each ITD. In contrast, ICcc neurons detect their preferred ITD in a single burst of stimulus. We recorded extracellularly the responses of LLDa neurons to ITD in anesthetized barn owls and show that this ability is already present in LLDa, raising the possibility that ICcc inherits its noise reduction property from LLDa.

Emergence of multiplicative auditory responses in the midbrain of the barn owl.

Space-specific neurons in the barn owl's auditory space map gain spatial selectivity through tuning to combinations of the interaural time difference (ITD) and interaural level difference (ILD). The combination of ITD and ILD in the subthreshold responses of space-specific neurons in the external nucleus of the inferior colliculus (ICx) is well described by a multiplication of ITD- and ILD-dependent components. It is unknown, however, how ITD and ILD are combined at the site of ITD and ILD convergence in the lateral shell of the central nucleus of the inferior colliculus (ICcl) and therefore whether ICx is the first site in the auditory pathway where multiplicative tuning to ITD- and ILD-dependent signals occurs. We used extracellular recording of single neurons to determine how ITD and ILD are combined in ICcl of the anesthetized barn owl (Tyto alba). A comparison of additive, multiplicative, and linear-threshold models of neural responses shows that ITD and ILD are combined nonlinearly in ICcl, but the interaction of ITD and ILD is not uniformly multiplicative over the sample. A subset (61%) of the neural responses is well described by the multiplicative model, indicating that ICcl is the first site where multiplicative tuning to ITD- and ILD-dependent signals occurs. ICx, however, is the first site where multiplicative tuning is observed consistently. A network model shows that a linear combination of ICcl responses to ITD-ILD pairs is sufficient to produce the multiplicative subthreshold responses to ITD and ILD seen in ICx.

Passive soma facilitates submillisecond coincidence detection in the owl's auditory system.

Neurons of the avian nucleus laminaris (NL) compute the interaural time difference (ITD) by detecting coincident arrivals of binaural signals with submillisecond accuracy. The cellular mechanisms for this temporal precision have long been studied theoretically and experimentally. The myelinated axon initial segment in the owl's NL neuron and small somatic spikes observed in auditory coincidence detector neurons of various animals suggest that spikes in the NL neuron are generated at the first node of Ranvier and that the soma passively receives back-propagating spikes. To investigate the significance of the "passive soma" structure, we constructed a two-compartment NL neuron model, consisting of a cell body and a first node, and systematically changed the excitability of each compartment. Here, we show that a neuron with a less active soma achieves higher ITD sensitivity and higher noise tolerance with lower energy costs. We also investigate the biophysical mechanism of the computational advantage of the "passive soma" structure by performing sub- and suprathreshold analyses. Setting a spike initiation site with high sodium conductance, not in the large soma but in the small node, serves to amplify high-frequency input signals and to reduce the impact and the energy cost of spike generation. Our results indicate that the owl's NL neuron uses a "passive soma" design for computational and metabolic reasons.

Connections of thalamic modulatory centers to the vocal control system of the zebra finch.

The vocal control system of zebra finches shows auditory gating in which neuronal responses to the individual bird's own song vary with behavioral states such as sleep and wakefulness. However, we know neither the source of gating signals nor the anatomical connections that could link the modulatory centers of the brain with the song system. Two of the song-control nuclei in the forebrain, the HVC (used as the proper name) and the interfacial nucleus of the nidopallium, both show auditory gating, and they receive input from the uvaeform nucleus (Uva) in the thalamus. We used a combination of anterograde and retrograde tracing methods to show that the dorsal part of the reticular formation and the medial habenula (MHb) project to the Uva. We also show by choline acetyl transferase immunohistochemistry that the MHb is cholinergic and sends cholinergic fibers to the Uva. Our findings suggest that the Uva might serve as a hub to coordinate neuromodulatory input into the song system.

Neural auditory selectivity develops in parallel with song.

The zebra finch learns his song by memorizing a tutor's vocalization and then using auditory feedback to match his current vocalization to this memory, or template. The neural song system of adult and young birds responds to auditory stimuli, and exhibits selective tuning to the bird's own song (BOS). We have directly examined the development of neural tuning in the song motor system. We measured song system responses to vocalizations produced at various ages during sleep. We now report that the auditory response of the song motor system and motor output are linked early in song development. During sleep, playback of the current BOS induced a response in the song nucleus HVC during the song practice period, even when the song consisted of little more than repeated begging calls. Halfway through the sensorimotor period when the song was not yet in its final form, the response to BOS already exceeded that to all other auditory stimuli tested. Moreover, responses to previous, plastic versions of BOS decayed over time. This indicates that selective tuning to BOS mirrors the vocalization that the bird is currently producing.

Neural song preference during vocal learning in the zebra finch depends on age and state.

The zebra finch acquires its song by first memorizing a model song from a tutor and then matching its own vocalizations to the memory trace of the tutor song, called a template. Neural mechanisms underlying this process require a link between the neural memory trace and the premotor song circuitry, which drives singing. We now report that a premotor song nucleus responds more to the tutor song model than to every other stimulus examined, including the bird's own song (BOS). Neural tuning to the song model occurred only during waking and peaked during the template-matching period of development, when the vocal motor output is sculpted to match the tutor song. During the same developmental phase, the BOS was the most effective excitatory stimulus during sleep. The preference for BOS compared to tutor song inverted with sleep/wake state. Thus, song preference shifts with development and state.

Robustness of multiplicative processes in auditory spatial tuning.

Auditory space-specific neurons in the owl's inferior colliculus selectively respond to the direction of sound propagation, which is defined by combinations of interaural time (ITD) and level (ILD) differences. Mathematical analyses show that the amplitude of postsynaptic potentials in these neurons is a product of two components that vary with either ITD or ILD. Temporal correlation in the fine structure of signals between the ears is essential for detection of ITD. By varying the degree of binaural correlation, we could accurately change the amplitude of the ITD component of postsynaptic potentials in the space-specific neurons. Multiplication worked for the entire range of postsynaptic potentials created by manipulation of ITD.

The role of auditory feedback in birdsong.

Young songbirds memorize a tutor song and use the memory trace as a template to shape their own song by auditory feedback. Major issues in birdsong research include the neural sites and mechanisms for song memory and auditory feedback. The brain song control system contains neurons with both premotor and auditory function. Yet no evidence so far shows that they respond to the bird's own song during singing. Also, no neurons have been found to respond to perturbation of auditory feedback in the brain area that is thought to be involved in the feedback control of song. The phenomenon of gating in which neurons respond to playback of the bird's own song only during sleep or under anesthesia is the sole known evidence for control of auditory input to the song system. It is, however, not known whether the gating is involved in switching between the premotor and auditory function of neurons in the song control system.

Coding of auditory space.

Behavioral, anatomical, and physiological approaches can be integrated in the study of sound localization in barn owls. Space representation in owls provides a useful example for discussion of place and ensemble coding. Selectivity for space is broad and ambiguous in low-order neurons. Parallel pathways for binaural cues and for different frequency bands converge on high-order space-specific neurons, which encode space more precisely. An ensemble of broadly tuned place-coding neurons may converge on a single high-order neuron to create an improved labeled line. Thus, the two coding schemes are not alternate methods. Owls can localize sounds by using either the isomorphic map of auditory space in the midbrain or forebrain neural networks in which space is not mapped.

Long memory in song learning by zebra finches.

Young songbirds use memorized tutor songs as templates to shape their own songs. This process requires control of voice by auditory feedback. We prevented zebra finches from hearing their own vocalizations by exposure to loud noise after 35 d of age, before which they had been reared with song tutors from birth. When the noise stopped at 102-200 d of age, the birds sang unstable and noisy song syllables that did not resemble the tutor syllables. The similarity to the tutor syllables steadily increased until the time of song crystallization approximately 30 d later. These findings show that the memory of tutor syllables survives auditory perturbations during the period when it is normally recalled and that zebra finches can use the memory well after the normal period of song development. The temporal order of syllables resembled the tutor model only in birds released from the noise before 80 d of age but not in older birds. Thus, different schedules and processes may govern the learning of syllable phonology and syntax.

From postsynaptic potentials to spikes in the genesis of auditory spatial receptive fields.

Space-specific neurons in the owl's inferior colliculus respond only to a sound coming from a particular direction, which is equivalent to a specific combination of interaural time difference (ITD) and interaural level difference (ILD). Comparison of subthreshold postsynaptic potentials (PSPs) and spike output for the same neurons showed that receptive fields measured in PSPs were much larger than those measured in spikes in both ITD and ILD dimensions. Space-specific neurons fire more spikes for a particular ITD than for its phase equivalents (ITD +/- 1/F, where F is best frequency). This differential response was much less pronounced in PSPs. The two sides of pyramid-shaped ILD curves were more symmetrical in spikes than in PSPs. Furthermore, monaural stimuli that were ineffective in eliciting spikes induced subthreshold PSPs. The main cause of these changes between PSPs and spikes is thresholding. The spiking threshold did not vary with the kind of acoustic stimuli presented. However, the thresholds of sound-induced first spikes were lower than those of later sound-induced and spontaneous spikes. This change in threshold may account for the sharpening of ITD selectivity during the stimulus. Large changes in receptive fields across single neurons are not unique to the owl's space-specific neurons but occur in mammalian visual and somatosensory cortices, suggesting the existence of general principles in the formation of receptive fields in high-order neurons.

Detection of large interaural delays and its implication for models of binaural interaction.

The interaural time difference (ITD) is a major cue to sound localization along the horizontal plane. The maximum natural ITD occurs when a sound source is positioned opposite to one ear. We examined the ability of owls and humans to detect large ITDs in sounds presented through headphones. Stimuli consisted of either broad or narrow bands of Gaussian noise, 100 ms in duration. Using headphones allowed presentation of ITDs that are greater than the maximum natural ITD. Owls were able to discriminate a sound leading to the left ear from one leading to the right ear, for ITDs that are 5 times the maximum natural delay. Neural recordings from optic-tectum neurons, however, show that best ITDs are usually well within the natural range and are never as large as ITDs that are behaviorally discriminable. A model of binaural crosscorrelation with short delay lines is shown to explain behavioral detection of large ITDs. The model uses curved trajectories of a cross-correlation pattern as the basis for detection. These trajectories represent side peaks of neural ITD-tuning curves and successfully predict localization reversals by both owls and human subjects.

Manipulation of inhibition in the owl's nucleus laminaris and its effects on optic tectum neurons.

Differences in arrival time and intensity (or level) of sound between the ears serve as cues for localization of sound in many animals. Barn owls use interaural time difference (ITD) and interaural level difference (ILD) for localization in azimuth and elevation, respectively. The owl's brain processes these two cues in separate pathways. The nucleus laminaris is the first site that detects ITDs by methods of delay lines and coincidence detection. The nucleus ventralis lemnisci lateralis, pars posterior is the first site of processing ILDs. The two pathways merge in the inferior colliculus to give rise to sensitivity to combinations of ITD and ILD. This selectivity is relayed to the optic tectum where neurons are sensitive to both visual and auditory stimuli. The present paper reports the results of manipulating inhibition in the nucleus laminaris and its effects on the optic tectum neurons. Injection of GABA or muscimol (a GABA(A) receptor agonist) in the nucleus laminaris reduces the responses of its neurons to ITD. This finding proves that GABA(A) receptor-mediated inhibition acts on the nucleus laminaris neurons. The same treatment did not affect the neurons of the nucleus ventralis lemnisci lateralis, pars posterior, whereas it reduced the response of the optic tectum neurons to ITD-ILD pairs. We conclude that although the two pathways are independent, the process of combining ITD and ILD creates a new relationship in which the output of the neuron varies with the amplitude of either input. This conclusion is consistent with the recent finding that the combination sensitivity is due to a multiplication of ITD and ILD inputs.

Deciphering the Brain's Codes.

The two sensory systems discussed in this review use similar algorithms for the synthesis of the neuronal selectivity for the stimulus that releases a particular behavior, although the neural circuits, the brain sites involved, and even the species are different. This stimulus selectivity emerges gradually in a neural network organized according to parallel and hierarchical design principles. The parallel channels contain lower order stations with special circuits for the creation of neuronal selectivities for different features of the stimulus. Convergence of the parallel pathways brings these selectivities together at a higher order station for the eventual synthesis of the selectivity for the whole stimulus pattern. The neurons that are selective for the stimulus are at the top of the hierarchy, and they form the interface between the sensory and motor systems or between sensory systems of different modalities. The similarities of these two systems at the level of algorithms suggest the existence of rules of signal processing that transcend different sensory systems and species of animals.