A topographic instructive signal guides the adjustment of the auditory space map in the optic tectum.

Maps of auditory space in the midbrain of the barn owl (Tyto alba) are calibrated by visual experience. When owls are raised wearing prismatic spectacles that displace the visual field in azimuth, the auditory receptive fields of neurons in the optic tectum shift to compensate for the optical displacement of the visual field. This shift results primarily from a shift in the tuning of tectal neurons for interaural time difference. The visually based instructive signal that guides this plasticity could be based on a topographic, point-by-point comparison between auditory and visual space maps or on a foveation-dependent visual assessment of the accuracy of auditory orienting responses. To distinguish between these two possibilities, we subjected owls to optical conditions that differed in the center of gaze and the visual periphery. A topographic signal would cause the portions of the space map representing the central and peripheral regions of visual space to adjust differently, according to the optical conditions that exist in each region. In contrast, a foveation-based signal would cause both portions of the map to adjust similarly, according to the optical conditions that exist at the center of gaze. In six of seven experiments, adaptive changes were as predicted by a topographic instructive signal. Although the results do not rule out the possible contribution of a foveation-based signal, they demonstrate that a topographic instructive signal is, indeed, involved in the calibration of the auditory space map in the barn owl optic tectum.

Gabaergic inhibition antagonizes adaptive adjustment of the owl's auditory space map during the initial phase of plasticity.

We studied the influence of GABA-mediated inhibition on adaptive adjustment of the owl's auditory space map during the initial phase of plasticity. Plasticity of the auditory space map was induced by subjecting owls to a chronic prismatic displacement of the visual field. In the initial stages of plasticity, inhibition suppressed responses to behaviorally appropriate, newly functional excitatory inputs. As a result, adaptive changes in excitatory input were only partially expressed as postsynaptic spike activity. This masking effect of inhibition on map plasticity did not depend on the activity of NMDA receptors at the synapses that supported the newly learned responses. On the basis of these results, we propose that the pattern of feedforward inhibition is less dynamic than the pattern of feedforward excitation at the site of plasticity. As a result, initially in the adjustment process the preexisting pattern of feedforward GABAergic inhibition opposes changes in the auditory space map and tends to preserve the established response properties of the network. The implications of this novel role of inhibition for the functional plasticity of the brain are discussed.

Early auditory experience induces frequency-specific, adaptive plasticity in the forebrain gaze fields of the barn owl.

Binaural acoustic cues such as interaural time and level differences (ITDs and ILDs) are used by many species to determine the locations of sound sources. The relationship between cue values and locations in space is frequency dependent and varies from individual to individual. In the current study, we tested the capacity of neurons in the forebrain localization pathway of the barn owl to adjust their tuning for binaural cues in a frequency-dependent manner in response to auditory experience. Auditory experience was altered by raising young owls with a passive acoustic filtering device that caused frequency-dependent changes in ITD and ILD. Extracellular recordings were made in normal and device-reared owls to characterize frequency-specific ITD and ILD tuning in the auditory archistriatum (AAr), an output structure of the forebrain localization pathway. In device-reared owls, individual sites in the AAr exhibited highly abnormal, frequency-dependent variations in ITD tuning, and across the population of sampled sites, there were frequency-dependent shifts in the representation of ITD. These changes were in a direction that compensated for the acoustic effects of the device on ITD and therefore tended to restore a normal representation of auditory space. Although ILD tuning was degraded relative to normal at many sites in the AAr of device-reared owls, the representation of frequency-specific ILDs across the population of sampled sites was shifted in the adaptive direction. These results demonstrate that early auditory experience shapes the representation of binaural cues in the forebrain localization pathway in an adaptive, frequency-dependent manner.

Adaptive adjustment of connectivity in the inferior colliculus revealed by focal pharmacological inactivation.

In the midbrain sound localization pathway of the barn owl, a map of auditory space is synthesized in the external nucleus of the inferior colliculus (ICX) and transmitted to the optic tectum. Early auditory experience shapes these maps of auditory space in part by modifying the tuning of the constituent neurons for interaural time difference (ITD), a primary cue for sound-source azimuth. Here we show that these adaptive modifications in ITD tuning correspond to changes in the pattern of connectivity within the inferior colliculus. We raised owls with an acoustic filtering device in one ear that caused frequency-dependent changes in sound timing and level. As reported previously, device rearing shifted the representation of ITD in the ICX and tectum but not in the primary source of input to the ICX, the central nucleus of the inferior colliculus (ICC). We applied the local anesthetic lidocaine (QX-314) iontophoretically in the ICC to inactivate small populations of neurons that represented particular values of frequency and ITD. We measured the effect of this inactivation in the optic tecta of a normal owl and owls raised with the device. In the normal owl, inactivation at a critical site in the ICC eliminated responses in the tectum to the frequency-specific ITD value represented at the site of inactivation in the ICC. The location of this site was consistent with the known pattern of ICC-ICX-tectum connectivity. In the device-reared owls, adaptive changes in the representation of ITD in the tectum corresponded to dramatic and predictable changes in the locations of the critical sites of inactivation in the ICC. Given that the abnormal representation of ITD in the tectum depended on frequency and was likely conveyed directly from the ICX, these results suggest that experience causes large-scale, frequency-specific adjustments in the pattern of connectivity between the ICC and the ICX.

Adaptive axonal remodeling in the midbrain auditory space map.

The auditory space map in the external nucleus of the inferior colliculus (ICX) of barn owls is highly plastic, especially during early life. When juvenile owls are reared with prismatic spectacles (prisms) that displace the visual field laterally, the auditory spatial tuning of neurons in the ICX adjusts adaptively to match the visual displacement. In the present study, we show that this functional plasticity is accompanied by axonal remodeling. The ICX receives auditory input from the central nucleus of the inferior colliculus (ICC) via topographic axonal projections. We used the anterograde tracer biocytin to study experience-dependent changes in the spatial pattern of axons projecting from the ICC to the ICX. The projection fields in normal adults were sparser and more restricted than those in normal juveniles. The projection fields in prism-reared adults were denser and broader than those in normal adults and contained substantially more bouton-laden axons that were appropriately positioned in the ICX to convey adaptive auditory spatial information. Quantitative comparison of results from juvenile and prism-reared owls indicated that prism experience led to topographically appropriate axonal sprouting and synaptogenesis. We conclude that this elaboration of axons represents the formation of an adaptive neuronal circuit. The density of axons and boutons in the normal projection zone was preserved in prism-reared owls. The coexistence of two different circuits encoding alternative maps of space may underlie the ability of prism-reared owls to readapt to normal conditions as adults.

Traces of learning in the auditory localization pathway.

One of the fascinating properties of the central nervous system is its ability to learn: the ability to alter its functional properties adaptively as a consequence of the interactions of an animal with the environment. The auditory localization pathway provides an opportunity to observe such adaptive changes and to study the cellular mechanisms that underlie them. The midbrain localization pathway creates a multimodal map of space that represents the nervous system's associations of auditory cues with locations in visual space. Various manipulations of auditory or visual experience, especially during early life, that change the relationship between auditory cues and locations in space lead to adaptive changes in auditory localization behavior and to corresponding changes in the functional and anatomical properties of this pathway. Traces of this early learning persist into adulthood, enabling adults to reacquire patterns of connectivity that were learned initially during the juvenile period.

Topographic projection from the optic tectum to the auditory space map in the inferior colliculus of the barn owl.

In the barn owl (Tyto alba), the external nucleus of the inferior colliculus (ICX) contains a map of auditory space that is calibrated by visual experience. The source of the visually based instructive signal to the ICX is unknown. Injections of biotinylated dextran amine and Fluoro-Gold in the ICX retrogradely labelled neurons in layers 8-15 of the ipsilateral optic tectum (OT) that could carry this instructive signal. This projection was point-to-point and in register with the feed-forward, auditory projection from the ICX to the OT. Most labelled neurons were in layers 10-11, and most were bipolar. Tripolar, multipolar, and unipolar neurons were also observed. Multipolar neurons had dendrites that were oriented parallel to the tectal laminae. In contrast, most labelled bipolar and tripolar neurons had dendrites oriented perpendicular to the tectal laminae, extending superficially into the retino-recipient laminae and deep into the auditory recipient laminae. Therefore, these neurons were positioned to receive both visual and auditory information from particular locations in space. Biocytin injected into the superficial layers of the OT labelled bouton-laden axons in the ICX. These axons were generally finer than, but had similar bouton densities as, feed-forward auditory fibers in the ICX, labelled by injections of biocytin into the central nucleus of the inferior colliculus (ICC). These data demonstrate a point-to-point projection from the OT to the ICX that could provide a spatial template for calibrating the auditory space map in the ICX.

A site of auditory experience-dependent plasticity in the neural representation of auditory space in the barn owl's inferior colliculus.

The barn owl's optic tectum contains a map of auditory space that is based, in part, on a map of interaural time difference (ITD). Previous studies have shown that this ITD map is shaped by auditory experience. In this study, we investigated whether the plasticity responsible for experience-induced changes in ITD tuning in the tectum occurs within the tectum itself or at an earlier stage in the auditory pathway. We altered auditory experience in young owls by implanting an acoustic filtering device in one ear that caused frequency-dependent changes in sound timing and level. We analyzed the representation of ITD in normal and device-reared owls in two nuclei in the ascending pathway: the external nucleus of the inferior colliculus (ICX), the primary source of ascending auditory input to the tectum, and the lateral shell of the central nucleus of the inferior colliculus (ICCls), the primary source of input to the ICX. In the ICX, device rearing caused adaptive, frequency-dependent changes in ITD tuning, as well as changes in frequency tuning. These changes in tuning were similar to changes that occurred in the optic tectum in the same owls. In contrast, in the ICCls, tuning for ITD and frequency was unaffected by device rearing. The data indicate that plasticity at the level of the ICX is largely responsible for the adaptive adjustments in ITD tuning and frequency tuning that are observed in the optic tecta of owls raised with abnormal auditory experience.

Abnormal auditory experience induces frequency-specific adjustments in unit tuning for binaural localization cues in the optic tectum of juvenile owls.

Early auditory experience shapes the auditory spatial tuning of neurons in the barn owl's optic tectum in a frequency-dependent manner. We examined the basis for this adaptive plasticity in terms of changes in tuning for frequency-specific interaural time differences (ITDs) and level differences (ILDs), the dominant sound localization cues. We characterized broadband and narrowband ITD and ILD tuning in normal owls and in owls raised with an acoustic filtering device in one ear that caused frequency-dependent changes in sound timing and level. In normal owls, units were tuned to frequency-specific ITD and ILD values that matched those produced by sound sources located in their visual receptive fields. In contrast, in device-reared owls, ITD tuning at most sites was shifted from normal by approximately 55 microsec toward open-ear leading for 4 kHz stimuli and 15 microsec toward the opposite-ear leading for 8 kHz stimuli, reflecting the acoustic effects of the device. ILD tuning was shifted in the adaptive direction by approximately 3 dB for 4 kHz stimuli and 8 dB for 8 kHz stimuli, but these shifts were substantially smaller than expected based on the acoustic effects of the device. Most sites also exhibited conspicuously abnormal frequency-response functions, including a strong dependence on stimulus ITD and a reduction of normally robust responses to 6 kHz stimuli. The results demonstrate that the response properties of high-order auditory neurons in the optic tectum are adjusted during development to reflect the influence of frequency-specific features of the binaural localization cues experienced by the individual.

Hearing impairment induces frequency-specific adjustments in auditory spatial tuning in the optic tectum of young owls.

Bimodal, auditory-visual neurons in the optic tectum of the barn owl are sharply tuned for sound source location. The auditory receptive fields (RFs) of these neurons are restricted in space primarily as a consequence of their tuning for interaural time differences and interaural level differences across broad ranges of frequencies. In this study, we examined the extent to which frequency-specific features of early auditory experience shape the auditory spatial tuning of these neurons. We manipulated auditory experience by implanting in one ear canal an acoustic filtering device that altered the timing and level of sound reaching the eardrum in a frequency-dependent fashion. We assessed the auditory spatial tuning at individual tectal sites in normal owls and in owls raised with the filtering device. At each site, we measured a family of auditory RFs using broadband sound and narrowband sounds with different center frequencies both with and without the device in place. In normal owls, the narrowband RFs for a given site all included a common region of space that corresponded with the broadband RF and aligned with the site's visual RF. Acute insertion of the filtering device in normal owls shifted the locations of the narrowband RFs away from the visual RF, the magnitude and direction of the shifts depending on the frequency of the stimulus. In contrast, in owls that were raised wearing the device, narrowband and broadband RFs were aligned with visual RFs so long as the device was in the ear but not after it was removed, indicating that auditory spatial tuning had been adaptively altered by experience with the device. The frequency tuning of tectal neurons in device-reared owls was also altered from normal. The results demonstrate that experience during development adaptively modifies the representation of auditory space in the barn owl's optic tectum in a frequency-dependent manner.

Mechanisms of experience-dependent plasticity in the auditory localization pathway of the barn owl.

Sound localization is a computational process that requires the central nervous system to measure various auditory cues and then associate particular cue values with appropriate locations in space. Behavioral experiments show that barn owls learn to associate values of cues with locations in space based on experience. The capacity for experience-driven changes in sound localization behavior is particularly great during a sensitive period that lasts until the approach of adulthood. Neurophysiological techniques have been used to determine underlying sites of plasticity in the auditory space-processing pathway. The external nucleus of the inferior colliculus (ICX), where a map of auditory space is synthesized, is a major site of plasticity. Experience during the sensitive period can cause large-scale, adaptive changes in the tuning of ICX neurons for sound localization cues. Large-scale physiological changes are accompanied by anatomical remodeling of afferent axons to the ICX. Changes in the tuning of ICX neurons for cue values involve two stages: (1) the instructed acquisition of neuronal responses to novel cue values and (2) the elimination of responses to inappropriate cue values. Newly acquired neuronal responses depend differentially on NMDA receptor currents for their expression. A model is presented that can account for this adaptive plasticity in terms of plausible cellular mechanisms.

Functional selection of adaptive auditory space map by GABAA-mediated inhibition.

The external nucleus of the inferior colliculus in the barn owl contains an auditory map of space that is based on the tuning of neurons for interaural differences in the timing of sound. In juvenile owls, this region of the brain can acquire alternative maps of interaural time difference as a result of abnormal experience. It has been found that, in an external nucleus that is expressing a learned, abnormal map, the circuitry underlying the normal map still exists but is functionally inactivated by inhibition mediated by gamma-aminobutyric acid type A (GABAA) receptors. This inactivation results from disproportionately strong inhibition of specific input channels to the network. Thus, experience-driven changes in patterns of inhibition, as well as adjustments in patterns of excitation, can contribute critically to adaptive plasticity in the central nervous system.

Maps versus clusters: different representations of auditory space in the midbrain and forebrain.

The auditory system determines the location of stimuli based on the evaluation of specific cues. The analysis begins in the tonotopic pathway, where these cues are processed in parallel, frequency-specific channels. This frequency-specific information is processed further in the midbrain and in the forebrain by specialized, space-processing pathways that integrate information across frequency channels, creating high-order neurons tuned to specific locations in space. Remarkably, the results of this integrative step are represented very differently in the midbrain and forebrain: in the midbrain, space is represented in maps, whereas, in the forebrain, space is represented in clusters of similarly tuned neurons. We propose that these different representations reflect the different roles that these two brain areas have in guiding behavior.

Early visual experience shapes the representation of auditory space in the forebrain gaze fields of the barn owl.

Auditory spatial information is processed in parallel forebrain and midbrain pathways. Sensory experience early in life has been shown to exert a powerful influence on the representation of auditory space in the midbrain space-processing pathway. The goal of this study was to determine whether early experience also shapes the representation of auditory space in the forebrain. Owls were raised wearing prismatic spectacles that shifted the visual field in the horizontal plane. This manipulation altered the relationship between interaural time differences (ITDs), the principal cue used for azimuthal localization, and locations of auditory stimuli in the visual field. Extracellular recordings were used to characterize ITD tuning in the auditory archistriatum (AAr), a subdivision of the forebrain gaze fields, in normal and prism-reared owls. Prism rearing altered the representation of ITD in the AAr. In prism-reared owls, unit tuning for ITD was shifted in the adaptive direction, according to the direction of the optical displacement imposed by the spectacles. Changes in ITD tuning involved the acquisition of unit responses to adaptive ITD values and, to a lesser extent, the elimination of responses to nonadaptive (previously normal) ITD values. Shifts in ITD tuning in the AAr were similar to shifts in ITD tuning observed in the optic tectum of the same owls. This experience-based adjustment of binaural tuning in the AAr helps to maintain mutual registry between the forebrain and midbrain representations of auditory space and may help to ensure consistent behavioral responses to auditory stimuli.

Sensitive periods for visual calibration of the auditory space map in the barn owl optic tectum.

Previous studies have identified sensitive periods for the developing barn owl during which visual experience has a powerful influence on the calibration of sound localization behavior. Here we investigated neural correlates of these sensitive periods by assessing developmental changes in the capacity of visual experience to alter the map of auditory space in the optic tectum of the barn owl. We used two manipulations. (1) We equipped owls with prismatic spectacles that optically displaced the visual field by 23 degrees to the left or right, and (2) we restored normal vision to prism-reared owls that had been raised wearing prisms. In agreement with previous behavioral experiments, we found that the capacity of abnormal visual experience to shift the tectal auditory space map was restricted to an early sensitive period. However, this period extended until later in life (approximately 200 d) than described previously in behavioral studies (approximately 70 d). Furthermore, unlike the previous behavioral studies that found that the capacity to recover normal sound localization after restoration of normal vision was lost at approximately 200 d of age, we found that the capacity to recover a normal auditory space map was never lost. Finally, we were able to reconcile the behaviorally and neurophysiologically defined sensitive periods by taking into account differences in the richness of the environment in the two sets of experiments. We repeated the behavioral experiments and found that when owls were housed in a rich environment, the capacity to adjust sound localization away from normal extended to later in life, whereas the capacity to recover to normal was never lost. Conversely, when owls were housed in an impoverished environment, the capacity to recover a normal auditory space map was restricted to a period ending at approximately 200 d of age. The results demonstrate that the timing and even the existence of sensitive periods for plasticity of a neural circuit and associated behavior can depend on multiple factors, including (1) the nature of the adjustment demanded of the system and (2) the richness of the sensory and social environment in which the plasticity is studied.

Pharmacological specialization of learned auditory responses in the inferior colliculus of the barn owl.

Neural tuning for interaural time difference (ITD) in the optic tectum of the owl is calibrated by experience-dependent plasticity occurring in the external nucleus of the inferior colliculus (ICX). When juvenile owls are subjected to a sustained lateral displacement of the visual field by wearing prismatic spectacles, the ITD tuning of ICX neurons becomes systematically altered; ICX neurons acquire novel auditory responses, termed "learned responses," to ITD values outside their normal, pre-existing tuning range. In this study, we compared the glutamatergic pharmacology of learned responses with that of normal responses expressed by the same ICX neurons. Measurements were made in the ICX using iontophoretic application of glutamate receptor antagonists. We found that in early stages of ITD tuning adjustment, soon after learned responses had been induced by experience-dependent processes, the NMDA receptor antagonist D, L-2-amino-5-phosphonopentanoic acid (AP-5) preferentially blocked the expression of learned responses of many ICX neurons compared with that of normal responses of the same neurons. In contrast, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked learned and normal responses equally. After long periods of prism experience, preferential blockade of learned responses by AP-5 was no longer observed. These results indicate that NMDA receptors play a preferential role in the expression of learned responses soon after these responses have been induced by experience-dependent processes, whereas later in development or with additional prism experience (we cannot distinguish which), the differential NMDA receptor-mediated component of these responses disappears. This pharmacological progression resembles the changes that occur during maturation of glutamatergic synaptic currents during early development.

Representation of binaural spatial cues in field L of the barn owl forebrain.

This study examined the representation of spatial information in the barn owl Field L, the first telencephalic processing stage of the classical auditory pathway. Field L units were recorded extracellularly, and their responses to dichotically presented interaural time differences (ITD) and interaural level differences (ILD) were tested. We observed a variety of tuning profiles in Field L. Some sites were not sensitive to ITD or ILD. Other sites, especially those in the high-frequency region, were highly selective for values of ITD and ILD. These sites had multipeaked (commonly called "phase ambiguous") ITD tuning profiles and were tuned for a single value of ILD. The tuning properties of these sites are similar to those seen in the lateral shell of the central nucleus of the inferior colliculus. Although the tuning properties of Field L sites were similar to those observed in the inferior colliculus, the functional organization of this spatial information was fundamentally different. Whereas in the inferior colliculus spatial information is organized into global topographics maps, in Field L spatial information is organized into local clusters, with sites having similar binaural tuning properties grouped together. The representation of binaural cues in Field L suggests that it is involved in auditory space processing but at a lower level of information processing than the auditory archistriatum, a forebrain area that is specialized for processing spatial information, and that the levels of information processing in the forebrain space processing pathway are remarkably similar to those in the well-known midbrain space processing pathway.

Forebrain pathway for auditory space processing in the barn owl.

The forebrain plays an important role in many aspects of sound localization behavior. Yet, the forebrain pathway that processes auditory spatial information is not known for any species. Using standard anatomic labeling techniques, we used a "top-down" approach to trace the flow of auditory spatial information from an output area of the forebrain sound localization pathway (the auditory archistriatum, AAr), back through the forebrain, and into the auditory midbrain. Previous work has demonstrated that AAr units are specialized for auditory space processing. The results presented here show that the AAr receives afferent input from Field L both directly and indirectly via the caudolateral neostriatum. Afferent input to Field L originates mainly in the auditory thalamus, nucleus ovoidalis, which, in turn, receives input from the central nucleus of the inferior colliculus. In addition, we confirmed previously reported projections of the AAr to the basal ganglia, the external nucleus of the inferior colliculus (ICX), the deep layers of the optic tectum, and various brain stem nuclei. A series of inactivation experiments demonstrated that the sharp tuning of AAr sites for binaural spatial cues depends on Field L input but not on input from the auditory space map in the midbrain ICX: pharmacological inactivation of Field L eliminated completely auditory responses in the AAr, whereas bilateral ablation of the midbrain ICX had no appreciable effect on AAr responses. We conclude, therefore, that the forebrain sound localization pathway can process auditory spatial information independently of the midbrain localization pathway.