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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.

Animals↗

Deficient auditory interhemispheric transfer in patients with PAX6 mutations.

PAX6 mutations are associated with absence/hypoplasia of the anterior commissure and reduction in the callosal area in humans. Both of these structures contain auditory interhemispheric fibers. The aim of this study was to characterize central auditory function in patients with a PAX6 mutation. We conducted central auditory tests (dichotic speech, pattern, and gaps in noise tests) on eight subjects with a PAX6 mutation and eight age- and sex-matched controls. Brain magnetic resonance imaging showed absent/hypoplastic anterior commissure in six and a hypoplastic corpus callosum in three PAX6 subjects. The control group gave normal central auditory tests results. All the PAX6 subjects gave abnormal results in at least two tests that require interhemispheric transfer, and all but one gave normal results in a test not requiring interhemispheric transfer. The left ear scores in the dichotic speech tests was significantly lower in the PAX6 than in the control group. These results are consistent with deficient auditory interhemispheric transfer in patients with a PAX6 mutation, which may be attributable to structural and/or functional abnormalities of the anterior commisure and corpus callosum, although the exact contribution of these two formations to our findings remains unclear. Our unique findings broaden the possible functions of PAX6 to include neurodevelopmental roles in higher order auditory processing.

Adult↗

Structure and function in the auditory system: From cochlea to cortex.

This special issue of the Anatomical Record examines the relationship between structure and function in the auditory system. Early anatomical studies defined this relationship on a macroscopic level and described the roles of structures such as the tympanic membrane, ossicular chain, Eustachian tube, and cochlea. As new tools emerged, the microscopic structure of the organ of Corti was described and later the brain stem regions involved in auditory processing were identified. Further technical advances allowed the description of cells within these central auditory regions in both morphological and physiological terms. More recently, studies of the auditory system have employed molecular biological techniques and novel imaging protocols. All these techniques continue to provide important insights into the structure and function of the auditory system on gross, cellular, and molecular levels. This issue expounds on this theme by demonstrating the importance of anatomy, whether the shape of the otic capsule or the sequence of a gene, in determining the function of the system and even the phenotype of the organism. The articles in this issue represent the cutting edge of today's auditory science and look back at the evolution of hearing and balance, as well as forward toward improving cochlear implant outcomes and gene therapies for treating sensorineural hearing loss.

Animals↗

Postnatal refinement of auditory nerve projections to the cochlear nucleus in cats.

Studies of visual system development have suggested that competition driven by activity is essential for refinement of initial topographically diffuse neuronal projections into their precise adult patterns. This has led to the assertion that this process may shape development of topographic connections throughout the nervous system. Because the cat auditory system is very immature at birth, with auditory nerve neurons initially exhibiting very low or no spontaneous activity, we hypothesized that the auditory nerve fibers might initially form topographically broad projections within the cochlear nuclei (CN), which later would become topographically precise at the time when adult-like frequency selectivity develops. In this study, we made restricted injections of Neurobiotin, which labeled small sectors (300-500 microm) of the cochlear spiral ganglion, to study the projections of auditory nerve fibers representing a narrow band of frequencies. Results showed that projections from the basal cochlea to the CN are tonotopically organized in neonates, many days before the onset of functional hearing and even prior to the development of spontaneous activity in the auditory nerve. However, results also demonstrated that significant refinement of the topographic specificity of the primary afferent axons of the auditory nerve occurs in late gestation or early postnatal development. Projections to all three subdivisions of the CN exhibit clear tonotopic organization at or before birth, but the topographic restriction of fibers into frequency band laminae is significantly less precise in perinatal kittens than in adult cats. Two injections spaced > or = 2 mm apart in the cochlea resulted in labeled bands of projecting axons in the anteroventral CN that were 53% broader than would be expected if they were proportional to those in adults, and the two projections were incompletely segregated in the youngest animals studied. Posteroventral CN (PVCN) projections (normalized for CN size) were 36% broader in neonates than in adults, and projections from double injections in the youngest subjects were nearly fused in the PVCN. Projections to the dorsal division of the CN were 32% broader in neonates than in adults when normalized, but the dorsal CN projections were always discrete, even at the earliest ages studied.

Aging↗

Regeneration of normal afferent input does not eliminate aberrant synaptic connections of an identified auditory interneuron in the cricket, Teleogryllus oceanicus.

In the cricket, Teleogryllus oceanicus, the dendritic arborizations of an identified auditory interneuron (Int-1) are normally restricted to the ipsilateral auditory neuropile; unilateral deafferentation causes the medial portion of the dendritic field to sprout across the midline and make functional connections with the contralateral auditory neuropile (Hoy et al., '78: Soc. Neurosci. Abstr. 4:115, '85: Proc. Natl. Acad. Sci. USA 82:7772-7786; Hoy and Moiseff, '79: Soc. Neurosci. Abstr. 5:163). We have found that regeneration of the auditory afferents also results in an aberrant pattern of innervation of Int-1. Crickets were unilaterally deafferented during postembryonic development by crushing or cutting the auditory nerve. Regeneration of afferent-to-Int-1 connections was tested behaviorally. Of 86 nerve-crushed crickets tested as adults in the behavioral assay, 66% showed functional regeneration of the afferents. Similar results were obtained from the nerve-cut group. However, morphological investigations demonstrated that most of the regenerates still retained the aberrant contralateral dendritic projection. Electrophysiological recordings from these Int-1s showed that not only are some of them driven by their regenerated auditory afferents (the normal pathway) but that they retain their excitability via their contralateral dendrites (the aberrant pathway). This demonstrates that reinnervation of Int-1 by its normal afferent pool neither causes retraction nor prevents the formation of connections made with foreign, contralateral afferents. When the contralateral afferent pool was removed after Int-1 had sprouted, the sprouts remained present, but preliminary results suggest that if the contralateral afferents are removed before Int-1 is deafferented, sprouts are not formed. The results are discussed in relation to the roles of competition and conservation of membrane area in controlling synapse formation.

Animals↗

Rapid changes in cochlear nucleus cell size following blockade of auditory nerve electrical activity in gerbils.

Large spherical cells of the mammalian anteroventral cochlear nucleus (AVCN) receive direct excitatory input from auditory nerve axons. Trans-synaptic regulation of neuronal cell size and cell number after cochlear ablation has been previously demonstrated in neonates of several vertebrate species, including the gerbil. Such changes may be related to loss of spontaneous or evoked auditory nerve electrical activity or to loss of activity-independent factors. We have developed a method to chronically, yet reversibly, block auditory nerve electrical activity without violating the integrity of the inner ear. Tetrodotoxin (TTX) was embedded in an ethylene-vinyl acetate copolymer resin (Elvax). A small piece of Elvax containing TTX was placed next to the round window membrane, which allowed TTX to diffuse into the inner ear. As a measure of the effectiveness of manipulation, the onset, duration, and magnitude of the auditory threshold shift were measured by the auditory brainstem response. The sound-evoked response was abolished within 10 minutes of placement of TTX on the round window membrane. The duration of threshold shift was dose-dependent and lasted 24-46 hours. Implants of Elvax without TTX did not produce a significant threshold shift. TTX, which blocks voltage-gated sodium channels, did not abolish the potassium-based cochlear microphonic response. The consequence of blocking afferent electrical activity on gerbil AVCN large spherical cells was examined by measuring their cross-sectional area after each of four manipulations: unilateral auditory nerve action potential blockade with TTX; unilateral surgical cochlear ablation; ipsilateral TTX exposure/contralateral cochlear ablation; and unilateral sham operation (Elvax without TTX).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Calcitonin-gene related peptide is an evolutionarily conserved marker within the amniote thalamo-telencephalic auditory pathway.

The distribution of neurons and fibers containing calcitonin-gene-related peptide (CGRP) was mapped in the thalamo-telencephalic auditory pathways of four amniote species, rats, pigeons (Columba livia), caiman (Caiman crocodilus), and turtles (Pseudemys scripta). In colchicine-treated turtles and pigeons, numerous CGRP+ perikarya were observed in the auditory relay nucleus of the thalamus (n. reuniens of reptiles, and n. ovoidalis of birds). In pigeons, these neurons were most abundant in the outer circumference of the nucleus and were not observed without colchicine pretreatment. In the telencephalon of turtles, caiman, and pigeons, CGRP+ fibers were observed within portions of the dorsal ventricular ridge previously shown to receive projections from the auditory thalamus, thus implying that the thalamic CGRP+ neurons observed here in fact project to these telencephalic areas. In colchicine treated rats, numerous CGRP+ perikarya were observed along the ventral margin of the medial geniculate nucleus extending into the posterior intralaminar and peripeduncular nuclei, as well as occasionally within the ventral subdivision of the medial geniculate nucleus. Injections of fluorogold into the auditory cortex combined with immunofluorescence labeling for CGRP revealed that CGRP+ cells in these areas do, in fact, project to the auditory cortices. The present results are interpreted as providing strong support for the theory, advanced previously, that the medial geniculate nucleus of mammals, nucleus ovoidalis of birds, and nucleus reuniens of reptiles contain at least some homologous cell populations. Although the data are consistent with the theory that the telencephalic projection fields are homologous, other interpretations are also consistent with the data presented here. These include the possibility that auditory thalamic projections to the telencephalon arose independently in the lines of evolution leading to mammals and sauropsids.

Alligators and Crocodiles↗

Topography of descending projections from the inferior colliculus to auditory brainstem nuclei in the rat.

We examined the organization of descending projections from the inferior colliculus (IC) to auditory brainstem nuclei and to pontine and reticular nuclei in the rat by employing the anterograde axonal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L). Small PHA-L injections into cytologically defined subnuclei of the IC revealed that each subnucleus has a unique pattern of efferent projections. The central nucleus of the IC projects in a topographic order to the dorsal nucleus of the lateral lemniscus (DLL), the rostral periolivary nucleus (RPO), the ventral nucleus of the trapezoid body (VNTB), and the dorsal cochlear nucleus (DCN). It is assumed that this topography represents a cochleotopic arrangement. The external cortex of the IC projects to the nucleus sagulum (Sag), the RPO, the VNTB, and the DCN. Minor projections were found to pontine and reticular nuclei. Efferent fibers from the dorsal cortex of the IC terminate mainly in the Sag, while other nuclei of the auditory and extra-auditory brainstem receive only minor projections. The intercollicular zone sends a moderate number of fibers to the DLL and very few, if any, to the remaining auditory brainstem nuclei. In contrast, fairly strong projections from the intercollicular zone to the reticular formation were found. The present data demonstrate that the four subnuclei of the IC have a differential pattern of descending projections to nuclei in the pontine and medullary brainstem. These parallel colliculofugal pathways, assumed to belong to functionally separate circuits, may modulate auditory processing at different levels of the auditory neuraxis.

Animals↗

Parvalbumin, calbindin D-28k, and calretinin immunoreactivity in the ascending auditory pathway of horseshoe bats.

In the subcortical auditory system of Rhinolophus rouxi, antibodies directed against the calcium-binding proteins parvalbumin, calbindin D-28k, and calretinin yield partly overlapping and partly complementary labeling patterns which are described in detail for each nucleus. The most general features of the labeling patterns are that: 1) Parvalbumin is a potent marker for large and heterogeneous populations of cells and puncta (presumed axon terminals) throughout the auditory pathway. 2) Immunostaining with the monoclonal calbindin-antiserum was typically absent or sparse in most auditory brainstem centers, but prominent in auditory nerve fibers and in cells of the medial geniculate body (MGB). 3) Calretinin label is abundant but more restricted to subsets of auditory nuclei or subpopulations of cells than parvalbumin. 4) Calcium-binding proteins are useful markers to define particular subregions or cell types in auditory nuclei: for example, i) different labeling patterns are obtained within the nuclei of the lateral lemniscus and adjacent tegmental zones; ii) in the inferior colliculus both calbindin- and calretinin-antisera yield similar regional specific staining patterns, but label different cell types; iii) subregions of the medial geniculate body have characteristic profiles of calcium-binding proteins; and iv) analyses of different nuclei showed that there is no simple common denominator for cells characterized by the expression of particular calcium-binding proteins, nor does labeling correspond in a straightforward way with specific functional systems. 5) there are profound differences between the calbindin labeling patterns seen in Rhinolophus and those in other mammals.

Animals↗

Growth of central nervous system auditory and visual nuclei in the postnatal gerbil (Meriones unguiculatus).

The objective of the present study was, by using the Mongolian gerbil (Meriones unguiculatus) as an animal model, to provide data on the growth dynamics of central auditory and visual nuclei and to relate the growth of these structures to the growth of the entire brain. So far, no such systematic study has been performed in any mammalian species. The knowledge of the rates of development of central nervous sensory structures might be useful for understanding the contribution of the central nervous system to maturation of sensory processing. Increases in volumes of nuclei and changes in their shape were analyzed for animals at the day of birth (P0); at postnatal days P7, P15, P22, P28; and in the third month (P90). The auditory nuclei investigated were the cochlear nucleus, the superior olivary complex, the nuclei of the lateral lemniscus, the inferior colliculus, and the medial geniculate body. From the visual system, the superior colliculus and the lateral geniculate body were studied. At P15 (shortly after the onset of central auditory responsiveness), the volumes of all auditory nuclei examined reached only 60-70% of their adult sizes; i.e., they showed considerable growth afterwards. At the same time (shortly before the animals open their eyes), the visual nuclei had almost reached their adult sizes (superior colliculus, 91%; lateral geniculate nucleus, 97%). These data demonstrate that different sensory nuclei contribute in highly different fashions to brain growth. There are system-specific differences in growth dynamics between central auditory and visual nuclei. However, the absolute growth of nuclei in both sensory systems relates to the brain regions. The data do not support the idea of a peripheral-to-central gradient in the growth of central auditory nuclei.

Aging↗

Subdivisions of macaque monkey auditory cortex revealed by calcium-binding protein immunoreactivity.

The aim of this investigation was to characterize auditory areas of the primate cerebral cortex on the basis of chemoarchitecture. Cortical areas of the supratemporal plane were delineated in Macaca fuscata (M. fuscata) by immunocytochemical staining for parvalbumin, staining for cytochrome oxidase, examination of cyto- and myeloarchitecture, and retrograde tracing of corticocortical connections. Comparative observations were made on Macaca fascicularis (M. fascicularis). Differential staining of fiber plexuses, probably of thalamic origin, identifies a central core zone of dense immunostaining and a surrounding zone of moderate-to-dense immunostaining composed of anteromedial, lateral, and posteromedial fields. Outside the second zone, there is a third anterolateral zone of weaker immunoreactivity, and, outside that zone, there is a fourth zone in which immunoreactivity is virtually absent. Differences in parvalbumin immunostaining in the auditory fields may reflect differences in relative contributions of thalamic inputs from parvalbumin-immunoreactive cells in the medial geniculate complex. The central core zone and the surrounding three fields can be correlated with major auditory fields previously defined by multiunit mapping and thalamocortical connectivity. The core zone contains a large principal field and an anterior extension. The pattern of corticocortical connections between these and adjoining fields suggests that the anteromedial, lateral, and posteromedial fields represent first steps in three streams of connections passing outward from auditory into association cortex. M. fuscata has an unusually large auditory cortex that is more deeply placed in the lateral sulcus in comparison to that of M. fascicularis. A small annectant gyrus provides a guide to the position of the primary auditory area.

Animals↗

Auditory thalamocortical pathways defined in monkeys by calcium-binding protein immunoreactivity.

This study investigated differentiation of Macaca fuscata auditory thalamus into chemically defined nuclei forming relays to auditory cortical areas. The thalamus was stained immunocytochemically for parvalbumin and 28 kDa calbindin in normals and in brains in which retrogradely transported tracers were injected into middle layers of auditory cortical areas or applied to the cortical surface. Parvalbumin- and calbindin-immunoreactive cells show a complementary distribution in ventral, anterodorsal, posterodorsal, and magnocellular medial geniculate nuclei. The ventral nucleus has a high density of parvalbumin cells and few calbindin cells, and the anterodorsal nucleus has a high density of parvalbumin cells and moderate numbers of calbindin cells. Both nuclei have a dense parvalbumin-immunoreactive neuropil formed by terminations of fibers ascending in the brachium of the inferior colliculus. The posterodorsal nucleus has approximately equal proportions of parvalbumin and calbindin cells; neuropil staining is weak but contains terminations of calbindin-immunoreactive fibers ascending in the midbrain tegmentum. The magnocellular nucleus contains domains of parvalbumin and calbindin cells. Parvalbumin cells in the ventral nucleus project to a central core of auditory cortex with densest parvalbumin immunoreactivity. Those in anterodorsal and posterodorsal nuclei project to surrounding auditory fields with less dense parvalbumin immunoreactivity; those in the magnocellular nucleus project widely to auditory and other fields. Injections of middle cortical layers label a large majority of parvalbumin cells in the ventral, anterodorsal, or posterodorsal nuclei and in the magnocellular nucleus. Superficial deposits label calbindin cells only, usually in more than one nucleus, implying a widespread projection system.

Animals↗

Cerebellum and auditory function: an ALE meta-analysis of functional neuroimaging studies.

Over the past two decades neuroimaging data have accumulated showing that the cerebellum, traditionally viewed only as a motor structure, is also active in a wide variety of sensory and cognitive tasks. We have proposed that instead of explicit involvement in any particular motor, sensory, or cognitive task, the cerebellum performs a much more fundamental computation involving the active acquisition of sensory data. We carried out an activation likelihood estimate (ALE) meta-analysis to determine whether neuroimaging results obtained during a wide range of auditory tasks support this proposal. Specifically, we analyzed the coordinates of 231 activation foci obtained in 15 different auditory studies selected through an extensive search of the positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) literature. The studies selected represent a wide variety of purely auditory tasks using highly controlled synthesized acoustic stimuli. The results clearly revealed that in addition to temporal auditory areas of cerebral cortex, specific regions in the cerebellum are activated consistently across studies regardless of the particular auditory task involved. In particular, one area in left lateral crus I area showed the greatest volume and ALE peak value among the extratemporal regions. A subanalysis was carried out that ruled out the specific association of this cerebellar cluster with attentional demand. The results are consistent with the hypothesis that the cerebellum may play a role in purely sensory auditory processing, and are discussed in light of the broader idea of the cerebellum subserving a fundamental sensory function.

Acoustic Stimulation↗

Alteration of auditory cortex activity with a visual stimulus through conditioning: a 2-deoxyglucose analysis.

In two experiments, the 2-deoxyglucose metabolic mapping technique was used to examine the hypothesis that a stimulus of one modality (a light) will begin to activate the sensory cortex of a stimulus of another modality (a tone) with which it has been repeatedly paired. Adult gerbils received repeated presentations of either a light or the light paired with a tone known to affect 2DG labeling patterns in the auditory cortex. Intermittent footshock was included on a pseudo-random basis to maintain arousal in the subjects. One day after training, each gerbil was injected with 2DG and either received repeated presentations of the light only or was simply exposed to the training context. Analysis of the auditory cortex revealed no differences in overall metabolic activity of the auditory cortex between the groups. However, in both experiments, the light that was previously paired with the tone changed the relative activity of the cortical subfields compared to the light not previously paired with the tone. Specifically, the results indicate greater activity in the anterior auditory field (AAF-Experiments 1 and 2) and the posterior fields (DPVP-Experiment 2) relative to the primary field AI in response to the light that was previously paired with the tone during training. Gerbils either only placed in the context during the 2DG session or that received unpaired presentations of the light and tone during training did not show this shift in relative labeling between the subfields. Because no differences in overall activity of the auditory cortex were found, we conclude that the shift in relative labeling between the subfields reflects, on average, both an increase in activity of fields AAF and DPVP and a concomitant decrease in AI activity in response to the light stimulus. The results have implications for our understanding both of brain learning mechanisms in general and the potential functions of auditory cortex subfields in particular.

Animals↗

A quantitative study of auditory-evoked saccadic eye movements in two dimensions.

We investigated the properties of human saccadic eye movements evoked by acoustic stimuli in the two-dimensional frontal plane. These movements proved to be quite accurate, both in azimuth and in elevation, provided the sound source spectrum had a broad bandwidth and a sufficiently long duration. If the acoustic target was a tone, the azimuth of the saccadic end points remained equally accurate, whereas the elevation of the response was related to the frequency of the tone, rather than to the physical position of the target. Saccade elevation accuracy also declined substantially for short-duration noise bursts, although response elevation remained highly correlated with target elevation. The latencies of auditory saccades depended on the amplitude, but not on the direction of the eye movement, suggesting a polar coordinate origin of auditory saccade initiation. We also observed that the trajectories of auditory saccades were often substantially curved. Both a qualitative and a model-based analysis showed that this curvature corrected for errors in the initial direction of the saccade. The latter analysis also suggested that the kinematic properties of auditory saccades could be described by the superposition of two overlapping saccadic eye movements, hypothesized to be based on binaural difference cues and monaural spectral cues in the auditory signal, respectively. It is argued that, although the audio-oculomotor system has to operate in a feedforward way, it must nevertheless have access to an accurate representation of actual and desired eye position. Different models underlying the generation of auditory saccades are discussed.

Adult↗

Organization of the auditory area in the posterior cerebellar vermis of the cat.

We mapped the topographic distribution of auditory responses in the posterior cerebellar vermis of the cat under barbiturate anesthesia. Auditory neurons in the granule cell layer of lobules VI and VII appeared to be arranged in columns perpendicular to the surface of the cerebellar cell layers. Mapping the surface of the cerebellum, auditory responses were found as separated patches of the order of a square millimeter. Neurons on these patches responded to auditory stimuli but neurons between patches did not respond to sound. In decerebrated cats, the entire granule cell layer within the cerebellar auditory area responded to acoustic stimulation without a patchy pattern. Responses to tonal stimuli from single neurons in the granule cell layer were studied before and after the induction of barbiturate anesthesia. Some neurons showed no change in their responses to sound before and under barbiturate. But other neurons showed dramatically attenuated responses or essentially stopped responding as a result of barbiturate anesthesia. These results suggest that there may be two types of granule cells distinguishable in their auditory responses and therefore possibly in function.

Acoustic Stimulation↗

Visual movement and pattern are important for the development of a map of auditory space in the guinea pig superior colliculus.

Previous data have indicated that, if guinea pigs are deprived of all visual information during a crucial period early in development (26-30 days after birth), the map of auditory space in the superior colliculus (SC) is completely disrupted. In the experiments reported here, multi-unit auditory receptive fields were recorded in the SC of two groups of anaesthetised guinea pigs that had been exposed to different forms of visual deprivation. One group was reared in a movement-free environment (strobe-reared) and the other group was reared in a pattern-free environment (their eyes covered with light-diffusing masks). Both groups experienced visual restriction during the crucial period for auditory space map development. In both experimental groups, the multi-unit auditory receptive fields were broad and all spatial tuning parameter values were significantly greater than the equivalent values from a control group of normal animals. In the pattern- and motion-deprived groups, a significant correlation existed between the rostro-caudal position of the recording electrode in the SC and the peak response angle of the receptive field, thus showing a degree of topographic organisation of the auditory receptive fields in the SC. However, the topographic order was less precise than that displayed by the control group of animals. These results indicate that, during development, both visual pattern and movement are important for the refinement of the SC auditory space map in the guinea pig.

Analysis of Variance↗

Somatostatin and leu-enkephalin in the rat auditory brainstem during fetal and postnatal development.

A transient expression of the neuropeptide somatostatin has been described in several brain areas during early ontogeny and several opioid peptides, such as leu-enkephalin, have also been found in the brain at this stage in development. It is therefore believed that somatostatin and leu-enkephalin may play a role in neural maturation. The aim of the present study was to describe the spatiotemporal pattern of somatostatin and leu-enkephalin immunoreactivity in the auditory brainstem nuclei of the developing rat and to correlate it with other developmental events. In order to achieve this goal, we applied peroxidase-antiperoxidase immunocytochemistry to rat brains between embryonic day (E) 17 and adulthood. Somatostatin immunoreactivity (SIR) was found in all nuclei of the auditory brainstem, yet it was temporally restricted in most nuclei. SIR appeared prenatally and reached maximum levels around postnatal day (P) 7, when great numbers of immunoreactive neurons were present in the ventral cochlear nucleus (VCN) and in the lateral lemniscus. At that time relatively low numbers of cells were labeled in the dorsal cochlear nucleus, the lateral superior olive (LSO), and the inferior colliculus (IC). During the same period, when somata in the VCN were somatostatin-immunoreactive (SIR), a dense network of labeled fibers was also present in the LSO, the medial superior olive (MSO), and the medial nucleus of the trapezoid body (MNTB). As these nuclei receive direct input from VCN neurons, and as the distribution and morphology of the somatostatinergic fibers in the superior olivary complex (SOC) was like that of axons from VCN neurons, these findings suggest a transient somatostatinergic connection within the auditory system. Aside from the LSO, MSO, and MNTB, labeled fibers were found to a smaller extent in all other auditory brainstem nuclei. After P7, the SIR decreased and only a few immunoreactive elements were found in the adult auditory brainstem nuclei, indicating that somatostatin is transiently expressed in the rat auditory brainstem. Leu-enkephalin immunoreactivity showed a lower number and weaker intensity of labeled structures as compared to SIR, with E18 being the earliest day at which labeled fibers appeared in the SOC. At birth, immunoreactive fibers were also present in the cochlear nuclear complex and in the IC. Leu-enkephalin immunoreactive somata were found only after P12 in the CN and after P16 in the IC. Leu-enkephalin immunoreactivity was not transient, but increased progressively with age until about P21, when the adult levels were reached.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗