Performing sound recognition is a task that requires an encoding of the time-varying spectral structure of the auditory stimulus. Similarly, computation of the interaural time difference (ITD) requires knowledge of the precise timing of the stimulus. Consistent with this, low-level nuclei of birds and mammals implicated in ITD processing encode the ongoing phase of a stimulus. However, the brain areas that follow the binaural convergence for the computation of ITD show a reduced capacity for phase locking. In addition, we have shown that in the barn owl there is a pooling of ITD-responsive neurons to improve the reliability of ITD coding. Here we demonstrate that despite two stages of convergence and an effective loss of phase information, the auditory system of the anesthetized barn owl displays a graceful transition to an envelope coding that preserves the spectrotemporal information throughout the ITD pathway to the neurons of the core of the central nucleus of the inferior colliculus.
Barn owls are capable of great accuracy in detecting the interaural time differences (ITDs) that underlie azimuthal sound localization. They compute ITDs in a circuit in nucleus laminaris (NL) that is reorganized with respect to birds like the chicken. The events that lead to the reorganization of the barn owl NL take place during embryonic development, shortly after the cochlear and laminaris nuclei have differentiated morphologically. At first the developing owl’s auditory brainstem exhibits morphology reminiscent of that of the developing chicken. Later, the two systems diverge, and the owl’s brainstem auditory nuclei undergo a secondary morphogenetic phase during which NL dendrites retract, the laminar organization is lost, and synapses are redistributed. These events lead to the restructuring of the ITD coding circuit and the consequent reorganization of the hindbrain map of ITDs and azimuthal space.
avian development; morphogenesis; auditory; laminaris; evolution; interaural time difference
Spatial receptive fields of neurons in the auditory pathway of the barn owl result from the sensitivity to combinations of interaural time (ITD) and level differences across stimulus frequency. Both the forebrain and tectum of the owl contain such neurons. The neural pathways, which lead to the forebrain and tectal representations of auditory space, separate before the midbrain map of auditory space is synthesized. The first nuclei that belong exclusively to either the forebrain or the tectal pathways are the nucleus ovoidalis (Ov) and the external nucleus of the inferior colliculus (ICx), respectively. Both receive projections from the lateral shell subdivision of the inferior colliculus but are not interconnected. Previous studies indicate that the owl’s tectal representation of auditory space is different from those found in the owl’s forebrain and the mammalian brain. We addressed the question of whether the computation of spatial cues in both pathways is the same by comparing the ITD tuning of Ov and ICx neurons. Unlike in ICx, the relationship between frequency and ITD tuning had not been studied in single Ov units. In contrast to the conspicuous frequency independent ITD tuning of space-specific neurons of ICx, ITD selectivity varied with frequency in Ov. We also observed that the spatially tuned neurons of Ov respond to lower frequencies and are more broadly tuned to ITD than in ICx. Thus there are differences in the integration of frequency and ITD in the two sound-localization pathways. Thalamic neurons integrate spatial information not only within a broader frequency band but also across ITD channels.
The brainstem auditory pathway is obligatory for all aural information. Brainstem auditory neurons must encode the level and timing of sounds, as well as their time-dependent spectral properties, the fine structure and envelope, which are essential for sound discrimination. This study focused on envelope coding in the two cochlear nuclei of the barn owl, nucleus angularis (NA) and nucleus magnocellularis (NM). NA and NM receive input from bifurcating auditory nerve fibers and initiate processing pathways specialized in encoding interaural time (ITD) and level (ILD) differences, respectively. We found that NA neurons, though unable to accurately encode stimulus phase, lock more strongly to the stimulus envelope than NM units. The spectrotemporal receptive fields (STRFs) of NA neurons exhibit a pre-excitatory suppressive field. Using multilinear regression analysis and computational modeling, we show that this feature of STRFs can account for enhanced across-trial response reliability, by locking spikes to the stimulus envelope. Our findings indicate a dichotomy in envelope coding between the time and intensity processing pathways as early as at the level of the cochlear nuclei. This allows the ILD processing pathway to encode envelope information with greater fidelity than the ITD processing pathway. Furthermore, we demonstrate that the properties of the neurons’ STRFs can be quantitatively related to spike timing reliability.
Nucleus angularis; STRF; spectrotemporal tuning; cochlear nuclei; barn owl; response reliability
The place theory proposed by Jeffress (1948) is still the dominant model of how the brain represents the movement of sensory stimuli between sensory receptors. According to the place theory, delays in signalling between neurons, dependent on the distances between them, compensate for time differences in the stimulation of sensory receptors. Hence the location of neurons, activated by the coincident arrival of multiple signals, reports the stimulus movement velocity. Despite its generality, most evidence for the place theory has been provided by studies of the auditory system of auditory specialists like the barn owl, but in the study of mammalian auditory systems the evidence is inconclusive. We ask to what extent the somatosensory systems of tactile specialists like rats and mice use distance dependent delays between neurons to compute the motion of tactile stimuli between the facial whiskers (or ‘vibrissae’). We present a model in which synaptic inputs evoked by whisker deflections arrive at neurons in layer 2/3 (L2/3) somatosensory ‘barrel’ cortex at different times. The timing of synaptic inputs to each neuron depends on its location relative to sources of input in layer 4 (L4) that represent stimulation of each whisker. Constrained by the geometry and timing of projections from L4 to L2/3, the model can account for a range of experimentally measured responses to two-whisker stimuli. Consistent with that data, responses of model neurons located between the barrels to paired stimulation of two whiskers are greater than the sum of the responses to either whisker input alone. The model predicts that for neurons located closer to either barrel these supralinear responses are tuned for longer inter-whisker stimulation intervals, yielding a topographic map for the inter-whisker deflection interval across the surface of L2/3. This map constitutes a neural place code for the relative timing of sensory stimuli.
To perceive how stimuli move over sensor surfaces like the retina or the fingertips, neurons in the brain must report the relative timing of signals arriving at different locations on the sensor surface. The rat whisker system is ideal for exploring how the brain performs this computation, because the layout of a small number of sensors (whiskers) maps directly onto the layout of corresponding columns of neurons in the sensory cortex. Previous studies have found that neurons located between adjacent cortical columns are most likely to respond when the corresponding adjacent whiskers are stimulated in rapid succession. These results suggest a link between the location of the neuron and the relative timing of sensory signals reported by its activity. We hypothesized that, if the time taken for whisker signals to arrive at a neuron is related to its distance from each cortical column, then neurons closer to a particular column will report stimuli moving towards that particular whisker. In a model approximating the geometry of cortical connections, responses of artificial neurons matched those of real neurons on a wide range of details. These results suggest an important role for neural geometry in neural computation.
Acoustic information is brought to the brain by auditory nerve fibers, all of which terminate in the cochlear nuclei, and is passed up the auditory pathway through the principal cells of the cochlear nuclei. A population of neurons variously known as T stellate, type I multipolar, planar multipolar, or chopper cells forms one of the major ascending auditory pathways through the brain stem. T Stellate cells are sharply tuned; as a population they encode the spectrum of sounds. In these neurons, phasic excitation from the auditory nerve is made more tonic by feed forward excitation, coactivation of inhibitory with excitatory inputs, relatively large excitatory currents through NMDA receptors, and relatively little synaptic depression. The mechanisms that make firing tonic also obscure the fine structure of sounds that is represented in the excitatory inputs from the auditory nerve and account for the characteristic chopping response patterns with which T stellate cells respond to tones. In contrast with other principal cells of the ventral cochlear nucleus (VCN), T stellate cells lack a low-voltage-activated potassium conductance and are therefore sensitive to small, steady, neuromodulating currents. The presence of cholinergic, serotonergic and noradrenergic receptors allows the excitability of these cells to be modulated by medial olivocochlear efferent neurons and by neuronal circuits associated with arousal. T Stellate cells deliver acoustic information to the ipsilateral dorsal cochlear nucleus (DCN), ventral nucleus of the trapezoid body (VNTB), periolivary regions around the lateral superior olivary nucleus (LSO), and to the contralateral ventral lemniscal nuclei (VNLL) and inferior colliculus (IC). It is likely that T stellate cells participate in feedback loops through both medial and lateral olivocochlear efferent neurons and they may be a source of ipsilateral excitation of the LSO.
ventral cochlear nucleus; brainstem auditory pathways; ion channels; patch-clamp recording
Male songbirds learn their songs from an adult tutor when they are young. A network of brain nuclei known as the ‘song system’ is the likely neural substrate for sensorimotor learning and production of song, but the neural networks involved in processing the auditory feedback signals necessary for song learning and maintenance remain unknown. Determining which regions show preferential responsiveness to the bird's own song (BOS) is of great importance because neurons sensitive to self-generated vocalisations could mediate this auditory feedback process. Neurons in the song nuclei and in a secondary auditory area, the caudal medial mesopallium (CMM), show selective responses to the BOS. The aim of the present study is to investigate the emergence of BOS selectivity within the network of primary auditory sub-regions in the avian pallium.
Methods and Findings
Using blood oxygen level-dependent (BOLD) fMRI, we investigated neural responsiveness to natural and manipulated self-generated vocalisations and compared the selectivity for BOS and conspecific song in different sub-regions of the thalamo-recipient area Field L. Zebra finch males were exposed to conspecific song, BOS and to synthetic variations on BOS that differed in spectro-temporal and/or modulation phase structure. We found significant differences in the strength of BOLD responses between regions L2a, L2b and CMM, but no inter-stimuli differences within regions. In particular, we have shown that the overall signal strength to song and synthetic variations thereof was different within two sub-regions of Field L2: zone L2a was significantly more activated compared to the adjacent sub-region L2b.
Based on our results we suggest that unlike nuclei in the song system, sub-regions in the primary auditory pallium do not show selectivity for the BOS, but appear to show different levels of activity with exposure to any sound according to their place in the auditory processing stream.
The barn owl is a well-known model system for studying auditory processing and sound localization. This article reviews the morphological and functional organization, as well as the role of the underlying microcircuits, of the barn owl's inferior colliculus (IC). We focus on the processing of frequency and interaural time (ITD) and level differences (ILD). We first summarize the morphology of the sub-nuclei belonging to the IC and their differentiation by antero- and retrograde labeling and by staining with various antibodies. We then focus on the response properties of neurons in the three major sub-nuclei of IC [core of the central nucleus of the IC (ICCc), lateral shell of the central nucleus of the IC (ICCls), and the external nucleus of the IC (ICX)]. ICCc projects to ICCls, which in turn sends its information to ICX. The responses of neurons in ICCc are sensitive to changes in ITD but not to changes in ILD. The distribution of ITD sensitivity with frequency in ICCc can only partly be explained by optimal coding. We continue with the tuning properties of ICCls neurons, the first station in the midbrain where the ITD and ILD pathways merge after they have split at the level of the cochlear nucleus. The ICCc and ICCls share similar ITD and frequency tuning. By contrast, ICCls shows sigmoidal ILD tuning which is absent in ICCc. Both ICCc and ICCls project to the forebrain, and ICCls also projects to ICX, where space-specific neurons are found. Space-specific neurons exhibit side peak suppression in ITD tuning, bell-shaped ILD tuning, and are broadly tuned to frequency. These neurons respond only to restricted positions of auditory space and form a map of two-dimensional auditory space. Finally, we briefly review major IC features, including multiplication-like computations, correlates of echo suppression, plasticity, and adaptation.
sound localization; central nucleus of the inferior colliculus; auditory; plasticity; adaptation; interaural time difference; interaural level difference; frequency tuning
How does the brain encode life experiences? Recent results derived from vital imaging, computational modeling, cellular physiology and systems neuroscience have pointed to local changes in synaptic connectivity as a powerful substrate, here termed micro-rewiring. To examine this hypothesis, I first review findings on micro-structural dynamics with focus on the extension and retraction of dendritic spines. Although these observations demonstrate a biological mechanism, they do not inform us of the specific changes in circuit configuration that might occur during learning. Here, computational models have made testable predictions for both the neuronal and circuit levels. Integrative approaches in the mammalian neocortex and the barn owl auditory localization pathway provide some of the first direct evidence in support of these ‘synaptic-clustering’ mechanisms. The implications of these data and the challenges for future research are discussed.
Learning rules, such as spike-timing-dependent plasticity (STDP), change the structure of networks of neurons based on the firing activity. A network level understanding of these mechanisms can help infer how the brain learns patterns and processes information. Previous studies have shown that STDP selectively potentiates feed-forward connections that have specific axonal delays, and that this underlies behavioral functions such as sound localization in the auditory brainstem of the barn owl. In this study, we investigate how STDP leads to the selective potentiation of recurrent connections with different axonal and dendritic delays during oscillatory activity. We develop analytical models of learning with additive STDP in recurrent networks driven by oscillatory inputs, and support the results using simulations with leaky integrate-and-fire neurons. Our results show selective potentiation of connections with specific axonal delays, which depended on the input frequency. In addition, we demonstrate how this can lead to a network becoming selective in the amplitude of its oscillatory response to this frequency. We extend this model of axonal delay selection within a single recurrent network in two ways. First, we show the selective potentiation of connections with a range of both axonal and dendritic delays. Second, we show axonal delay selection between multiple groups receiving out-of-phase, oscillatory inputs. We discuss the application of these models to the formation and activation of neuronal ensembles or cell assemblies in the cortex, and also to missing fundamental pitch perception in the auditory brainstem.
Our brain's ability to perform cognitive processes, such as object identification, problem solving, and decision making, comes from the specific connections between neurons. The neurons carry information as spikes that are transmitted to other neurons via connections with different strengths and propagation delays. Experimentally observed learning rules can modify the strengths of connections between neurons based on the timing of their spikes. The learning that occurs in neuronal networks due to these rules is thought to be vital to creating the structures necessary for different cognitive processes as well as for memory. The spiking rate of populations of neurons has been observed to oscillate at particular frequencies in various brain regions, and there is evidence that these oscillations play a role in cognition. Here, we use analytical and numerical methods to investigate the changes to the network structure caused by a specific learning rule during oscillatory neural activity. We find the conditions under which connections with propagation delays that resonate with the oscillations are strengthened relative to the other connections. We demonstrate that networks learn to oscillate more strongly to oscillations at the frequency they were presented with during learning. We discuss the possible application of these results to specific areas of the brain.
The physical arrangement of receptive fields (RFs) within neural structures is important for local computations. Nonuniform distribution of tuning within populations of neurons can influence emergent tuning properties, causing bias in local processing. This issue was studied in the auditory system of barn owls. The owl’s external nucleus of the inferior colliculus (ICx) contains a map of auditory space where the frontal region is overrepresented. We measured spatiotemporal RFs of ICx neurons using spatial white noise. We found a population-wide bias in surround suppression such that suppression from frontal space was stronger. This asymmetry increased with laterality in spatial tuning. The bias could be explained by a model of lateral inhibition based on the overrepresentation of frontal space observed in ICx. The model predicted trends in surround suppression across ICx that matched the data. Thus, the uneven distribution of spatial tuning within the map could explain the topography of time-dependent tuning properties. This mechanism may have significant implications for the analysis of natural scenes by sensory systems.
Sound localization; spatiotemporal receptive field; inferior colliculus; barn owl; surround bias
The steroid hormone estradiol plays an important role in reproductive development and behavior and modulates a wide array of physiological and cognitive processes. Recently, reports from several research groups have converged to show that estradiol also powerfully modulates sensory processing, specifically, the physiology of central auditory circuits in songbirds. These investigators have discovered that (1) behaviorally-relevant auditory experience rapidly increases estradiol levels in the auditory forebrain; (2) estradiol instantaneously enhances the responsiveness and coding efficiency of auditory neurons; (3) these changes are mediated by a non-genomic effect of brain-generated estradiol on the strength of inhibitory neurotransmission; and (4) estradiol regulates biochemical cascades that induce the expression of genes involved in synaptic plasticity. Together, these findings have established estradiol as a central regulator of auditory function and intensified the need to consider brain-based mechanisms, in addition to peripheral organ dysfunction, in hearing pathologies associated with estrogen deficiency.
17β-Estradiol; Audition; Selectivity; Fadrozole; Estrogen; Aromatase; Behavior; Vocal learning; Selectivity; Auditory coding
The auditory system encodes time with sub-millisecond accuracy. To shed new light on the basic mechanism underlying this precise temporal neuronal coding, we analyzed the neurophonic potential, a characteristic multiunit response, in the barn owl’s nucleus laminaris. We report here that the relative time measure of phase delay is robust against changes in sound level, with a precision sharper than 20 µs. Absolute measures of delay, such as group delay or signal-front delay, had much greater temporal jitter, for example due to their strong dependence on sound level. Our findings support the hypothesis that phase delay underlies the sub-millisecond precision of the representation of interaural time difference needed for sound localization.
The classic estrogen 17β-estradiol (E2) was recently identified as a novel modulator of hearing function. It is produced rapidly, in an experience-dependent fashion, by auditory cortical neurons of both males and females. This brain-generated E2 enhances the efficiency of auditory coding and improves the neural and behavioral discrimination of auditory cues. Remarkably, the effects of E2 are long-lasting and persist for hours after local rises in hormone levels have subsided. The mechanisms and functional consequences of this E2-induced plasticity of auditory responses are unknown. Here, we addressed these issues in the zebra finch model by combining intracerebral pharmacology, biochemical assays, in vivo neurophysiology in awake animals, and computational and information theoretical approaches. We show that auditory experience activates the MAPK pathway in an E2-dependent manner. This effect is mediated by estrogen receptor β (ERβ), which directly associates with MEKK1 to sequentially modulate MEK and ERK activation, where the latter is required for the engagement of downstream molecular targets. We further show that E2-mediated activation of the MAPK cascade is required for the long-lasting enhancement of auditory-evoked responses in the awake brain. Moreover, a functional consequence of this E2/MAPK activation is to sustain enhanced information handling and neural discrimination by auditory neurons for several hours following hormonal challenge. Our results demonstrate that brain-generated E2 engages, via a nongenomic interaction between an estrogen receptor and a kinase, a persistent form of experience-dependent plasticity that enhances the neural coding and discrimination of behaviorally relevant sensory signals in the adult vertebrate brain.
The mechanisms by which the brain selects a particular stimulus as the next target for gaze are poorly understood. A cholinergic nucleus in the owl’s midbrain exhibits functional properties that suggest its role in bottom-up stimulus selection. Neurons in the nucleus isthmi pars parvocellularis (Ipc) respond to wide ranges of visual and auditory features, but they are not tuned to particular values of those features. Instead, they encode the relative strengths of stimuli across the entirety of space. Many neurons exhibit switch-like properties, abruptly increasing their responses to a stimulus in their receptive field when it becomes the strongest stimulus. This information propagates directly to the optic tectum, a structure involved in gaze control and stimulus selection, as periodic (25–50 Hz) bursts of cholinergic activity. The functional properties of Ipc neurons resemble those of a “salience map”, a core component in computational models for spatial attention and gaze control.
Owls are known for their silent flight. Even though there is some information available on the mechanisms that lead to a reduction of noise emission, neither the morphological basis, nor the biological mechanisms of the owl's silent flight are known. Therefore, we have initiated a systematic analysis of wing morphology in both a specialist, the barn owl, and a generalist, the pigeon. This report presents a comparison between the feathers of the barn owl and the pigeon and emphasise the specific characteristics of the owl's feathers on macroscopic and microscopic level. An understanding of the features and mechanisms underlying this silent flight might eventually be employed for aerodynamic purposes and lead to a new wing design in modern aircrafts.
A variety of different feathers (six remiges and six coverts), taken from several specimen in either species, were investigated. Quantitative analysis of digital images and scanning electron microscopy were used for a morphometric characterisation. Although both species have comparable body weights, barn owl feathers were in general larger than pigeon feathers. For both species, the depth and the area of the outer vanes of the remiges were typically smaller than those of the inner vanes. This difference was more pronounced in the barn owl than in the pigeon. Owl feathers also had lesser radiates, longer pennula, and were more translucent than pigeon feathers. The two species achieved smooth edges and regular surfaces of the vanes by different construction principles: while the angles of attachment to the rachis and the length of the barbs was nearly constant for the barn owl, these parameters varied in the pigeon. We also present a quantitative description of several characteristic features of barn owl feathers, e.g., the serrations at the leading edge of the wing, the fringes at the edges of each feather, and the velvet-like dorsal surface.
The quantitative description of the feathers and the specific structures of owl feathers can be used as a model for the construction of a biomimetic airplane wing or, in general, as a source for noise-reducing applications on any surfaces subjected to flow fields.
The KCNC1 (previously Kv3.1) potassium channel, a delayed rectifier with a high threshold of activation, is highly expressed in the time coding nuclei of the adult chicken and barn owl auditory brainstem. The proposed role of KCNC1 currents in auditory neurons is to reduce the width of the action potential and enable neurons to transmit high frequency temporal information with little jitter. Because developmental changes in potassium currents are critical for the maturation of the shape of the action potential, we used immunohistochemical methods to examine the developmental expression of KCNC1 subunits in the avian auditory brainstem. The KCNC1 gene gives rise to two splice variants, a longer KCNC1b and a shorter KCNC1a that differ at the carboxy termini. Two antibodies were used: an antibody to the N-terminus that does not distinguish between KCNC1a and b isoforms, denoted as panKCNC1, and another antibody that specifically recognizes the C terminus of KCNC1b. A comparison of the staining patterns observed with the pan-KCNC1 and the KCNC1b specific antibodies suggests that KCNC1a and KCNC1b splice variants are differentially regulated during development. Although pan-KCNC1 immunoreactivity is observed from the earliest time examined in the chicken (E10), a subcellular redistribution of the immunoproduct was apparent over the course of development. KCNC1b specific staining has a late onset with immunostaining first appearing in the regions that map high frequencies in nucleus magnocellularis (NM) and nucleus laminaris (NL). The expression of KCNC1b protein begins around E14 in the chicken and after E21 in the barn owl, relatively late during ontogeny and at the time that synaptic connections mature morphologically and functionally.
chicken; barn owl; ontogeny; time coding; outward current; high threshold
In the precedence effect, sounds emanating directly from the source are localized preferentially over their reflections. Although most studies have focused on the delay between the onset of a sound and its echo, humans still experience the precedence effect when this onset delay is removed. We tested in barn owls the hypothesis that an ongoing delay, equivalent to the onset delay, is discernible from the envelope features of amplitude-modulated stimuli and may be sufficient to evoke this effect. With sound pairs having only envelope cues, owls localized direct sounds preferentially and neurons in their auditory space-maps discharged more vigorously to them, but only if the sounds were amplitude modulated. Under conditions that yielded the precedence effect, acoustical features known to evoke neuronal discharges were more abundant in the envelopes of the direct sounds than of the echoes, suggesting that specialized neural mechanisms for echo suppression were unnecessary.
Inhibitory transmission is critical to sensory and motor processing and is believed to play a role in experience-dependent plasticity. The main inhibitory neurotransmitter in vertebrates, GABA, has been implicated in both sensory and motor aspects of vocalization in songbirds. To understand the role of GABAergic mechanisms in vocal communication, GABAergic elements must be characterized fully. Hence, we investigated GABA immunohistochemistry in the zebra finch brain, emphasizing auditory areas and song control nuclei. Several nuclei of the ascending auditory pathway showed a moderate to high density of GABAergic neurons including the cochlear nuclei, nucleus laminaris, superior olivary nucleus, mesencephalic nucleus lateralis pars dorsalis, and nucleus ovoidalis. Telencephalic auditory areas, including field L subfields L1, L2a and L3, as well as the caudomedial nidopallium (NCM) and mesopallium (CMM), contained GABAergic cells at particularly high densities. Considerable GABA labeling was also seen in the shelf area of caudodorsal nidopallium, and the cup area in the arcopallium, as well as in area X, the lateral magnocellular nucleus of the anterior nidopallium, the robust nucleus of the arcopallium and nidopallial nucleus HVC. GABAergic cells were typically small, most likely local inhibitory interneurons, although large GABA-positive cells that were sparsely distributed were also identified. GABA-positive neurites and puncta were identified in most nuclei of the ascending auditory pathway and in song control nuclei. Our data are in accordance with a prominent role of GABAergic mechanisms in regulating the neural circuits involved in song perceptual processing, motor production, and vocal learning in songbirds.
GAD; Avian; NCM; Songbird; Plasticity; HVC
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.
In order to localize sounds in the environment, the auditory system detects and encodes differences in signals between each ear. The exquisite sensitivity of auditory brain stem neurons to the differences in rise time of the excitation signals from the two ears allows for neuronal encoding of microsecond interaural time differences.
Low-frequency sound localization depends on the neural computation of interaural time differences (ITD) and relies on neurons in the auditory brain stem that integrate synaptic inputs delivered by the ipsi- and contralateral auditory pathways that start at the two ears. The first auditory neurons that respond selectively to ITD are found in the medial superior olivary nucleus (MSO). We identified a new mechanism for ITD coding using a brain slice preparation that preserves the binaural inputs to the MSO. There was an internal latency difference for the two excitatory pathways that would, if left uncompensated, position the ITD response function too far outside the physiological range to be useful for estimating ITD. We demonstrate, and support using a biophysically based computational model, that a bilateral asymmetry in excitatory post-synaptic potential (EPSP) slopes provides a robust compensatory delay mechanism due to differential activation of low threshold potassium conductance on these inputs and permits MSO neurons to encode physiological ITDs. We suggest, more generally, that the dependence of spike probability on rate of depolarization, as in these auditory neurons, provides a mechanism for temporal order discrimination between EPSPs.
Animals can locate the source of a sound by detecting microsecond differences in the arrival time of sound at the two ears. Neurons encoding these interaural time differences (ITDs) receive an excitatory synaptic input from each ear. They can perform a microsecond computation with excitatory synapses that have millisecond time scale because they are extremely sensitive to the input's “rise time,” the time taken to reach the peak of the synaptic input. Current theories assume that the biophysical properties of the two inputs are identical. We challenge this assumption by showing that the rise times of excitatory synaptic potentials driven by the ipsilateral ear are faster than those driven by the contralateral ear. Further, we present a computational model demonstrating that this disparity in rise times, together with the neurons' sensitivity to excitation's rise time, can endow ITD-encoding with microsecond resolution in the biologically relevant range. Our analysis also resolves a timing mismatch. The difference between contralateral and ipsilateral latencies is substantially larger than the relevant ITD range. We show how the rise time disparity compensates for this mismatch. Generalizing, we suggest that phasic-firing neurons—those that respond to rapidly, but not to slowly, changing stimuli—are selective to the temporal ordering of brief inputs. In a coincidence-detection computation the neuron will respond more robustly when a faster input leads a slower one, even if the inputs are brief and have similar amplitudes.
Auditory processing and hearing-related pathologies are heavily influenced by steroid hormones in a variety of vertebrate species including humans. The hormone estradiol has been recently shown to directly modulate the gain of central auditory neurons, in real-time, by controlling the strength of inhibitory transmission via a non-genomic mechanism. The functional relevance of this modulation, however, remains unknown. Here we show that estradiol generated in the songbird homologue of the mammalian auditory association cortex, rapidly enhances the effectiveness of the neural coding of complex, learned acoustic signals in awake zebra finches. Specifically, estradiol increases mutual information rates, coding efficiency and the neural discrimination of songs. These effects are mediated by estradiol’s modulation of both rate and temporal coding of auditory signals. Interference with the local action or production of estradiol in the auditory forebrain of freely-behaving animals disrupts behavioral responses to songs, but not to other behaviorally-relevant communication signals. Our findings directly show that estradiol is a key regulator of auditory function in the adult vertebrate brain.
17β-estradiol; vocal learning; audition; coding; information; auditory discrimination; ATD; fadrozole; plasticity
The cochlear nucleus angularis (NA) is widely assumed to form the starting point of a brain stem pathway for processing sound intensity in birds. Details of its function are unclear, however, and its evolutionary origin and relationship to the mammalian cochlear-nucleus complex are obscure. We have carried out extracellular single-unit recordings in the NA of ketamine-anesthetized barn owls. The aim was to re-evaluate the extent of heterogeneity in NA physiology because recent studies of cellular morphology had established several distinct types. Extensive characterization, using tuning curves, phase locking, peristimulus time histograms and rate-level functions for pure tones and noise, revealed five major response types. The most common one was a primary-like pattern that was distinguished from auditory-nerve fibers by showing lower vector strengths of phase locking and/or lower spontaneous rates. Two types of chopper responses were found (chopper-transient and a rare chopper-sustained), as well as onset units. Finally, we routinely encountered a complex response type with a pronounced inhibitory component, similar to the mammalian typeIV. Evidence is presented that this range of response types is representative for birds and that earlier conflicting reports may be due to methodological differences. All five response types defined were similar to well-known types in the mammalian cochlear nucleus. This suggests convergent evolution of neurons specialized for encoding different behaviorally relevant features of the auditory stimulus. It remains to be investigated whether the different response types correlate with morphological types and whether they establish different processing streams in the auditory brain stem of birds.
The classic steroid hormone estradiol is rapidly produced by central auditory neurons in the songbird brain and instantaneously modulates auditory coding to enhance the neural and behavioral discrimination of acoustic signals. Although these recent advances highlight novel roles for estradiol in the regulation of central auditory processing, current knowledge on the functional and neurochemical organization of estrogen-associated circuits, as well as the impact of sensory experience in these auditory forebrain networks, remains very limited. Here we show that both estrogen-producing and -sensitive neurons are highly expressed in the caudomedial nidopallium (NCM), the zebra finch analog of the mammalian auditory association cortex, but not other auditory forebrain areas. We further demonstrate that auditory experience primarily engages estrogen-producing, and to a lesser extent, estrogen-responsive neurons in NCM, that these neuronal populations moderately overlap, and that acute episodes of sensory experience do not quantitatively affect these circuits. Finally, we show that whereas estrogen-producing cells are neurochemically heterogenous, estrogen-sensitive neurons are primarily glutamatergic. These findings reveal the neurochemical and functional organization of estrogen-associated circuits in the auditory forebrain, demonstrate their activation and stability in response to sensory experience in behaving animals, and highlight estrogenic circuits as fundamental components of central networks supporting sensory processing.
17β-estradiol; NCM; estrogen; avian
Song in oscine birds is a learned behavior that plays important roles in breeding. Pronounced seasonal differences in song behavior, and in the morphology and physiology of the neural circuit underlying song production are well documented in many songbird species. Androgenic and estrogenic hormones largely mediate these seasonal changes. While much work has focused on the hormonal mechanisms underlying seasonal plasticity in songbird vocal production, relatively less work has investigated seasonal and hormonal effects on songbird auditory processing, particularly at a peripheral level. We addressed this issue in Gambel’s white-crowned sparrow (Zonotrichia leucophrys gambelii), a highly seasonal breeder. Photoperiod and hormone levels were manipulated in the laboratory to simulate natural breeding and non-breeding conditions. Peripheral auditory function was assessed by measuring the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) of males and females in both conditions. Birds exposed to breeding-like conditions demonstrated elevated thresholds and prolonged peak latencies compared with birds housed under non-breeding-like conditions. There were no changes in DPOAEs, however, which indicates that the seasonal differences in ABRs do not arise from changes in hair cell function. These results suggest that seasons and hormones impact auditory processing as well as vocal production in wild songbirds.
songbird; hormone; season; auditory; ABR