Organisation and maturation of the human thalamus as revealed by CD15

The distribution of the CD15 antigen (CD15, 3-fucosyl-N-acetyl-lactosamine, Lewis x) has been studied immunohistochemically in the fetal human thalamus. Its changing patterns could be related to three successive, but overlapping, periods primarily due to its association with radial glial cells, neuropil, and neural cell bodies, respectively. From 9 weeks of gestation (wg), a subset of CD15-positive radial glial cells distinguished the neuroepithelium of the ventral thalamus, a characteristic also seen in the developing mouse. Distal processes of the radial glial cells converged at the root of the forebrain choroid tenia, which was also CD15 positive. From 13 wg until approximately 20 wg, CD15-positive neuropil labeling marked the differentiation areas of prospective nuclei within the dorsal thalamus and progressively outlined their territories in a time sequence, which appeared specific for each nucleus. CD15 labeling of differentiating nuclei of the ventral, medial, anterior, and intralaminar thalamic divisions showed a transient topographic relationship with restricted areas of the ventricular wall. After 26 wg, CD15 immunoreactivity was observed in subpopulations of glial cells and neurons. Transient CD15 immunoreactivity was also found in delimited compartments within the subventricular region. The time of CD15 expression, its location, and cellular association suggest that CD15 is involved in segmentation of diencephalon, in the specification of differentiating nuclear areas and initial processes regarding the formation of intercellular contacts and cellular maturation.     

The subcortical auditory structures in the Mongolian gerbil: II. Frequency‐related topography of the connections with cortical field AI

We investigated the frequency‐related topography of connections of the primary auditory cortical field (AI) in the Mongolian gerbil with subcortical structures of the auditory system by means of the axonal transport of two bidirectional tracers, which were simultaneously injected into regions of AI with different best frequencies (BFs). We found topographic, most likely frequency‐matched (tonotopic) connections as well as non‐topographic (non‐tonotopic) connections. AI projects in a tonotopic way to the ipsilateral ventral (MGv) and dorsal divisions (MGd) of the medial geniculate body (MGB), the reticular thalamic nucleus and dorsal nucleus of the lateral lemniscus, and the ipsi‐ and contralateral dorsal cortex of the inferior colliculus (IC) and central nucleus of the IC. AI receives tonotopic inputs from MGv and MGd. Projections from different BF regions of AI terminate in a non‐tonotopic way in the ipsilateral medial division of the MGB (MGm), the suprageniculate thalamic nucleus (SG) and brachium of the IC (bic), and the ipsi‐ and contralateral external cortex and pericollicular areas of the IC. The anterograde labeling in the intermediate and ventral nucleus of the lateral lemniscus, parts of the superior olivary complex, and divisions of the cochlear nucleus was generally sparse; thus a clear topographic arrangement of the labeled axons could not be ruled out. AI receives non‐tonotopic inputs from the ipsilateral MGm, SG, and bic. In conclusion, the tonotopic and non‐tonotopic corticofugal connections of AI can potentially serve for both conservation and integration of frequency‐specific information in the respective target structures. J. Comp. Neurol. 521:2772–2797, 2013. © 2013 Wiley Periodicals, Inc.     

Localization of GABA immunoreactivity in the auditory brainstem of guinea pigs

Using an antibody against GABA, neurons within the guinea pig hindbrain, midbrain and forebrain auditory nuclei were identified which demonstrate GABA-like immunoreactivity. GABA-positive cells were localized in the cochlear nucleus, superior olivary complex, lateral lemniscus, inferior colliculus, and medial geniculate body. GABA-positive terminals could be seen surrounding globular and spherical cells in ventral cochlear nucleus and principal cells in medial nucleus of the trapezoid body. In addition, numerous positive, punctate terminals appeared throughout the hindbrain auditory nuclei and, although fewer in number, in midbrain and forebrain auditory nuclei.     

Fibroblast growth factor-2-like immunoreactivity in auditory brainstem nuclei of the developing and adult rat: Correlation with onset and loss of hearing

Fibroblast growth factor-2 (FGF-2; basic FGF) is widely distributed in the developing and adult brain and has numerous effects on cultured and lesioned neural cells. The physiological role of FGF-2 in the unlesioned nervous system, however, is still not understood. We have studied the distribution of FGF-2 in the developing, adult, and functionally impaired central auditory system of the rat using specific antibodies and peroxidase-antiperoxidase immunocytochemistry. FGF-2-like immunoreactivity (FGF-2-IR) occurred in neuronal cell bodies and/or nerve fibers but was very rarely observed in glial cells. Several auditory brainstem nuclei, including the superior paraolivary nucleus, the medial superior olive, the lateral and ventral trapezoid nuclei, and the central nucleus, as well as the external cortex of the inferior colliculus, were entirely devoid of FGF-2-IR. In the dorsal cochlear nucleus, the lateral superior olive, and the nuclei of the lateral lemniscus, FGF-2-IR was not detectable in nerve cell bodies prior to adult age. Neurons in the medial geniculate body exhibited FGF-2-IR only transiently, from postnatal day (P) 5 until P16. Neurons in the medial nucleus of the trapezoid body were immunoreactive from P8 onwards. FGF-2-IR in anteroventral and posteroventral cochlear neurons disappeared at P14, i. e., at the onset of hearing, but immunoreactivity returned after P21. A transient expression of FGF-2 around the time when hearing function commences was observed in the dorsal cortex of the inferior colliculus. Thus, regulation of neuronal FGF-2-IR in several, but not all, auditory, nuclei is related to the onset of hearing, in that IR disappears at that time or transiently appears. This suggests a causal link between the onset of hearing and FGF-2 expression. In support of this notion, ototoxic treatment with gentamycin abolished FGF-2-IR in the P16 medial geniculate body but not in other auditory brainstem centers. Thus, FGF-2 may be considered a regulator or indicator of the acquisition of functional activity and responsiveness to sensory stimuli in several areas of the auditory system. © 1995 Wiley-Liss, Inc.     

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, post and magriocellular 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 approxi mately equal proportions of parvalbumin and calbindin cells; neuropil staining is weak but contains terminations of calbindin-immunoreactive fibers ascending in the midbrain tegmenturn. 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. © Wiley-Liss, Inc.     

GAD- and GABA-immunoreactivity in the ascending auditory pathway of horseshoe and mustached bats.

A comparative study of the immunostain to antibodies directed against glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid (GABA) in the ascending auditory pathway was carried out in horseshoe bats (Rhinolophus rouxi) and mustached bats (Pteronotus parnellii). In both species GAD/GABA-positive puncta (presumed axonal boutons) and GAD/GABA-positive cells were found in the cochlear nucleus, the superior olivary complex, the nuclei of the lateral lemniscus the inferior colliculus, and the medial geniculate body. General features of the immunostaining pattern in the auditory pathway agree with observations in other mammals. Quantitative analysis of puncta distribution shows that many auditory centers are characterized by subregional differences in puncta density and distribution. This indicates local differences in putatively inhibitory input related to connectivity and tonotopic organization. The following species characteristic features were found: 1) The dorsal non-laminated portion of the dorsal cochlear nucleus in horseshoe bats lacks the GAD/GABA-immunoreactive cells typical for the ventral laminated portion and the dorsal cochlear nucleus of other species. Clearly, a cytoarchitectonic specialization is accompanied by a loss of putatively GABAergic local inhibitory circuits. 2) The ventral division of the medial geniculate body of the mustached bat lacks GAD/GABA-immunopositive cells. Such cells are present in the horseshoe bat and other mammals. This finding implies functional differences in the organization of the medial geniculate body within the same mammalian order.     

Acoustic brainstem nuclei express Fos after flurothyl-induced generalized seizures in rats

The inferior colliculus (IC) plays a key role in modulating audiogenic seizures (AS) in rats. We investigated whether acoustic brainstem nuclei express Fos-like immunoreactivity (FLI) after flurothyl-induced generalized seizures in rats. Compared to controls, experimental animals showed significantly (P<0.05) more FLI in the dorsal and external cortex of the IC, as well as in the medial part of the medial geniculate body (MGB), perigeniculate area, and dorsal cochlear nucleus. No significant increase of FLI was observed in the central nucleus of the IC, ventral and dorsal parts of the MGB, dorsal nucleus of the lateral lemniscus, or ventral cochlear nucleus. Because this pattern of FLI closely resembles that observed after AS in previous studies, these results suggest that Fos expression in acoustic brainstem nuclei is not specific for AS.     

Development of calretinin immunoreactivity in the brainstem auditory nuclei of the barn owl (Tyto alba).

The early development of calretinin immunoreactivity (CR-IR) was described in the auditory nuclei of the brainstem of the barn owl. CR-IR was first observed in the auditory hindbrain at embryonic day (E17) and a day later (E18) in the inferior colliculus. In each of the auditory nuclei studied, CR-IR did not develop homogeneously, but began in the regions that map high best frequencies in the adult barn owl. In the hindbrain, CR-IR was first observed in the rostromedial regions of the cochlear nucleus magnocellularis and the nucleus laminaris, and in the dorsal regions of the nucleus angularis and in the nucleus of the lateral lemniscus. In the inferior colliculus, CR-IR began in the ventral region of the central core. The edge of these gradients moved along the future tonotopic axes during the development of all nuclei studied, until adult patterns of CR-IR were achieved about a week after hatching.     

A golgi study of the medial geniculate body in the tree shrew (Tupaia glis)

The subdivisions of the medial geniculate body in Tupaia recognized in previous connectional and cytoarchitectural studies are identified in Golgi-impregnated material. They may be distinguished by the organization of the neuropil, especially the dendrites, and, in many cases, by differences in the neurons. The ventral nucleus contains tufted cells with disc-shaped dendritic fields which are aligned to form laminae. The caudomarginal and deep dorsal nuclei have less tufted, less precisely arranged cells with longer, thin appendages. Neurons in the suprageniculate and dorsal nuclei are similar except that they apparently are arranged more randomly and tend to have more spherically shaped dendritic fields. The medial division is characterized rostrally by the presence of stellate cells and caudally by large cells which appear to be the neurons, observed in previous studies to have widespread connections. The results of this Golgi study suggest that the subdivisions of the medial geniculate body might be grouped differently than in previous reports. When combined with data from previous studies of connections, the results show that the medial geniculate body of even distantly related species may follow a common plan. The ventral nucleus is the medial geniculate component of the central pathway which extends from the central nucleus of the inferior colliculus to the primary auditory cortex. Most of the other medial geniculate subdivisions participate in either pericentral pathways originating in the cortex and other nuclei which surround the central nucleus of the inferior colliculus or in the pathways of the lateral midbrain tegmentum. Pericentral and lateral tegmental pathways terminate in nonprimary auditory cortex. The widespread pathway involves only the caudal nucleus of the medial division. It receives afferents from most, if not all, of the midbrain regions that give rise to the other pathways and distributes to all parts of the auditory cortex where it terminates in layers other than layer III-IV.     

Distribution of corticotropin-releasing factor mRNA and immunoreactivity in the central auditory system of the rat.

Hybridization histochemical and immunohistochemical methods were used to characterize the distribution of corticotropin-releasing factor (CRF) messenger RNA (mRNA) and peptide, respectively, in the central auditory system of the rat. Cell bodies expressing CRF mRNA and/or immunoreactivity (IR) were detected at each level of the system, including sparse or equivocal localizations in the dorsal cochlear nucleus, the medial nucleus of the trapezoid body, and the lateral superior olive. More prominent groups of cells expressing CRF mRNA and CRF-IR were found in the nuclei of the lateral lemniscus, the shell of the inferior colliculus, the medial division of the medial geniculate body and in primary auditory cortices. The latter showed the greatest density of CRF-expressing interneurons, distributed primarily in layers II, III and V, of any neocortical area. Results obtained using the two staining methods were in good agreement, except in the cochlear and superior olivary nuclei, where cells displaying CRF-IR were apparent in far greater abundance than those expressing CRF mRNA. CRF-IR fibers and terminals were detected in regions generally consistent with the cellular localizations described above. These results provide evidence for a surprisingly widespread expression of CRF in the auditory system of the rat. This includes generally low levels of expression in components of the primary auditory path (cochlear nucleus, trapezoid body, superior olive, lemniscal nuclei). CRF appears to be more prominently expressed in so-called non-primary components of the auditory system, including aspects of the medial geniculate body that constitute an interface between the auditory system and stress-related limbic system circuitry.     

Deafness in Cockayne's syndrome: Morphological,morphometric, and quantitative study of the auditory pathway

The auditory pathway of a 17-year-old deaf patient with Cockayne's syndrome was examined histologically. The cochlea showed marked atrophy of the spiral ganglion and attenuation of the cochlear division of the eighth cranial nerve. By means of the Computer Image Analyzer, the total number of neurons in the ventral cochlear nucleus was found to be reduced from 30,440 to 18,821. The mean diameter of the neurons in the ventral cochlear nucleus, medial dorsal olivary nucleus, and inferior colliculus was smaller than in a control patient, whereas in the medial geniculate nucleus and anterior transverse gyrus of Heschl, the neuronal size approximated the norm. The changes in the first three auditory relay nuclei were considered to represent transsynaptic atrophy caused by degeneration of the spiral ganglion and, possibly, the cochlear neuroepithelium. This histological report verifies that deafness in Cockayne's syndrome is largely sensorineural and that degeneration of spiral ganglion in humans can lead to a chain of trans-synaptic degeneration in the ventral cochlear nucleus, medial dorsal olivary nucleus, and inferior colliculus.     

Primary auditory cortex in the rat: transient expression of acetylcholinesterase activity in developing geniculocortical projections

A characteristic pattern of acetylcholinesterase (AChE) activity is expressed transiently in primary auditory cortex (cortical area 41) of developing laboratory rats during early postnatal life. This AChE activity occurs as a dense plexus in cortical layer IV and the deep part of layer III. This transient band of AChE activity is first detected by histochemical techniques on postnatal day (P) 3, reaches peak intensity at approximately P8-10, and declines to form the adult pattern by P23. The ventral nucleus of the medial geniculate body of the thalamus also displays prominent, and transient, staining for AChE. This intense staining for AChE, found within neuronal somata and neuropil, is detected at the time of birth, reaches peak intensity around P8, and declines to adult levels by P16. The areal and laminar patterns of the transient band of AChE activity in temporal cortex correspond to the patterns of anterograde transneuronal labeling of geniculocortical terminals following injection of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the inferior colliculus. Placement of lesions that include the medial geniculate nucleus or the geniculocortical axons results in a marked decrease in AChE staining in thalamorecipient layers of auditory cortex. Placement of lesions that include the medial globus pallidus reduce AChE staining of some axons in temporal cortex of developing rats, but the dense band of AChE in layers III and IV remains. Placement of lesions in the inferior colliculus in newborn animals results in marked decrease in AChE staining in cells of the ipsilateral ventral medial geniculate nucleus and in ipsilateral auditory cortex of developing pups. These data indicate that transiently expressed AChE activity is characteristic of geniculocortical neurons, including their somata in the medial geniculate body and their terminal axons in primary auditory cortex. This AChE activity is expressed early in postnatal development, probably during the time when thalamocortical axons are proliferating in cortical layer IV and forming synaptic contacts with cortical neurons.     

Regional cerebral palmitate incorporation after unilateral auditory deprivation in immature and adult Fischer-344 rats

Regional cerebral incorporation of intravenously injected [U-14C]palmitate was measured from 1 day to 13 weeks after left cochlear destruction in 11-day- and 3 month-old, awake Fischer-344 rats. In 11-day-old animals, statistically significant left-right differences in incorporation were absent 1 day after cochlear destruction and were found only in parts of the cochlear nucleus and inferior colliculus after 1 week. After 6 to 13 weeks, consistent with functional neuroanatomy of central auditory regions, incorporation was reduced by 6 to 9% in the left cochlear nucleus and left lateral superior olivary nucleus, compared with corresponding right-side regions. The right medial superior olivary nucleus, medial nucleus of the trapezoid body, lateral lemniscus nucleus, inferior colliculus, medial geniculate body, and auditory cortex had 5 to 9% less incorporation than did corresponding left-side regions. Fewer significant differences after chronic auditory deprivation occurred in 3-month-old rats than in 11-day-old rats following cochlear destruction. Reduced incorporation corresponded to reported changes in cell morphology, which also were greater in immature than mature rats following auditory deprivation. The results suggest that the palmitate method can be used to identify long-term regional changes in the turnover of brain lipids after sensory deprivation.     

Age-related changes in the distribution of Kv1.1 and Kv3.1 in rat cochlear nuclei

OBJECTIVES: To identify age-related changes in voltage-gated K(+) (Kv) channels that contribute to temporal processing in neurons of the central auditory system, we investigated the distribution of Kv1.1 and Kv3.1 in the auditory brainstem of adult and aged rats. METHODS: Immunohistochemistry was performed in accordance with the free-floating method described earlier. RESULTS: Among the auditory nuclei, only the posterior ventral cochlear nucleus (PVCN) showed age-related changes. Kv1.1 immunoreactivity was increased in the octopus cell bodies, while the staining intensity was significantly decreased in the neuropil. Image analysis demonstrated the specific increase in Kv1.1 immunoreactivity in aged cochlear nucleus neurons although the mean density of the entire selection was significantly decreased. In contrast, the number of Kv1.1-immunoreactive neurons was not significantly different between control and aged groups. The immunoreactivity for Kv3.1 was decreased in the octopus cells and neuropil of aged PVCN, which was confirmed by image analysis. The number of Kv3.1-positive cells was also significantly decreased in aged PVCN. DISCUSSION: This study may provide useful data to compare age-related changes in Kv1.1 and Kv3.1 with known physiological properties of auditory neurons.     

Corticofugal modulation of acoustically induced Fos expression in the rat auditory pathway

To investigate the corticofugal modulation of acoustic information ascending through the auditory pathway of the rat, immunohistochemical techniques were used to study the functional expression of Fos protein in neurons. With auditory stimulation at different frequencies, Fos expression in the medial geniculate body (MGB), inferior colliculus (IC), superior olivary complex, and cochlear nucleus was examined, and the extent of Fos expression on the two sides was compared. Strikingly, we found densely Fos-labeled neurons in all divisions of the MGB after both presentation of an auditory stimulus and administration of a gamma-aminobutyric acid type A (GABA(A)) antagonist (bicuculline methobromide; BIM) to the auditory cortex. The location of Fos-labeled neurons in the ventral division (MGv) after acoustic stimulation at different frequencies was in agreement with the known tonotopic organization. That no Fos-labeled neurons were found in the MGv with acoustic stimuli alone suggests that the transmission of ascending thalamocortical information is critically governed by corticofugal modulation. The dorsal (DCIC) and external cortices (ECIC) of the IC ipsilateral to the BIM-injected cortex showed a significantly higher number of Fos-labeled neurons than the contralateral IC. However, no difference in the number of Fos-labeled neurons was found between the central nucleus of the IC on either side, indicating that direct corticofugal modulation occurs only in the ECIC and DCIC. Further investigations are needed to assess the functional implications of the morphological differences observed between the descending corticofugal projections to the thalamus and the IC.     

Developmental expression of the glycine transporter GLYT2 in the auditory system of rats suggests involvement in synapse maturation.

The synaptic action of many neurotransmitters is terminated by specific transporters that remove the molecules from the synaptic cleft and help to replenish the transmitter supply. Here, we have investigated the spatiotemporal distribution of the glycine transporter GLYT2 in the central auditory system of rats, where glycinergic synapses are abundant. In adult rats, GLYT2 immunoreactivity was found at all relay stations, except the auditory cortex. Many immunoreactive puncta surrounded the neuronal somata in the cochlear nuclear complex, the superior olivary complex, and the nuclei of the lateral lemniscus. In contrast, diffuse neuropil labeling was seen in the inferior colliculus and the medial geniculate body. The punctate perisomatic labeling and the diffuse neuropil labeling were very similar to the staining pattern described previously with glycine antibodies in the auditory system, suggesting that GLYT2 is a reliable marker for glycinergic synapses. However, there was a discrepancy between cytoplasmic GLYT2 and glycine labeling, as not all neuron types previously identified with glycine antibodies displayed somatic GLYT2 immunoreactivity. During development, GLYT2 immunoreactivity appeared between embryonic days 18 and 20, i.e., shortly after the time when the earliest functional synapses have been established in the auditory system. Labeling turned from a diffuse pattern to a clustered, punctate appearance. The development was also characterized by an increase of the signal intensity, which generally lasted until about postnatal day 10. Thereafter, a decrease occurred until about postnatal day 21, when the mature pattern was established in most nuclei. Because of the perinatal onset of GLYT2 immunoreactivity, we speculate that the transporter molecules participate in the process of early synapse maturation.     

Immunolocalization of PICK1 in the ascending auditory pathways of the adult rat

Protein that interacts with C-kinase alpha (PICK1) is a PDZ domain protein that interacts with many binding partners in the central nervous system (CNS), including activated protein kinase Calpha and subunits of the AMPA subtype of glutamate receptor. Almost nothing is known about the anatomic distribution of PICK1 in the intact adult CNS. By using PICK1 antisera and peroxidase immunocytochemistry, we report on the distribution of PICK1 in the ascending pathways of the central auditory system of the adult rat. PICK1-immunoreactivity (ir) was observed in many component nuclei of the central auditory system, including the dorsal cochlear nucleus, anteroventral cochlear nucleus, posteroventral cochlear nucleus, some divisions of the superior olivary complex, inferior colliculus, medial geniculate body, and primary auditory cortex. The general staining pattern for PICK1-immunoreactivity was somatodendritic with scattered puncta in neuropil and somatodendritic regions. The distribution of PICK1 partially overlaps with PKCalpha and glutamate receptor subunits such as GluR2. These data suggest that PICK1 may function in the regulation of PKCalpha and GluR2 localization in components of the rat auditory system, which may be a fundamental mechanism of synaptic transmission and/or plasticity. J. Comp. Neurol.     

Differential molecular profiles of astrocytes in degeneration and re‐innervation after sensory deafferentation of the adult rat cochlear nucleus

Ablating the cochlea causes total sensory deafferentation of the cochlear nucleus. Over the first postoperative week, degeneration of the auditory nerve and its synaptic terminals in the cochlear nucleus temporally overlaps with its re‐innervation by axon collaterals of medial olivocochlear neurons. At the same time, astrocytes increase in size and density. We investigated the time courses of the expression of ezrin, polysialic acid, matrix metalloprotease‐9 and matrix metalloprotease‐2 within these astrocytes during the first week following cochlear ablation. All four proteins are known to participate in degeneration, regeneration, or both, following injury of the central nervous system. In a next step, stereotaxic injections of kainic acid were made into the ventral nucleus of the trapezoid body prior to cochlear ablation to destroy the neurons that re‐innervate the deafferented cochlear nucleus by axon collaterals developing growth‐associated protein 43 immunoreactivity. This experimental design allowed us to distinguish between molecular processes associated with degeneration and those associated with re‐innervation. Under these conditions, astrocytic growth and proliferation showed an unchanged deafferentation‐induced pattern. Similarly, the distribution and amount of ezrin and matrix metalloprotease‐9 in astrocytes after cochlear ablation developed in the same way as under cochlear ablation alone. In sharp contrast, the astrocytic expression of polysialic acid and matrix metalloprotease‐2 normally invoked by cochlear ablation collapsed when re‐innervation of the cochlear nucleus was inhibited by lesioning medial olivocochlear neurons with kainic acid. In conclusion, re‐innervation, including axonal growth and synaptogenesis, seems to prompt astrocytes to recompose their molecular profile, paving the way for tissue reorganisation after nerve degeneration and loss of synaptic contacts.     

Tonotopic Order in the Adult and Developing Auditory System of the Rat as Shown by c-fos Immunocytochemistry

Immediate éarly genes such as the proto-oncogene c- fos can be expressed in neurons following synaptic excitation by sensory stimulation. C- fos immunocytochemistry has subsequently been shown to be a very sensitive marking technique for neuronal activity. Here, antibodies against the c- fos protein product Fos were used to map the tonotopic organization in the auditory system of adult and developing rats. After stimulating adult rats with pure-tone pulses, bands of Fos-immunoreactive neurons revealed the frequency representation in seven brainstem nuclei: all three subdivisions of the cochlear nucleus, the lateral superior olive, the medial nucleus of the trapezoid body, the ventral nucleus of the trapezoid body, the rostral periolivary nucleus, the dorsal nucleus of the lateral lemniscus and the inferior colliculus. With the exception of the dorsal cochlear nucleus and the inferior colliculus, tonotopicity has not been previously demonstrated in the brainstem nuclei of the rat. During development two striking results were obtained. First, beginning at postnatal day 14 (i.e. ∼2 days after physiological hearing begins in rats), not only low but also high frequencies were able to induce strong Fos immunoreactivity, indicating that gradual recruitment of formerly unresponsive high-frequency sites does not occur in the rat. Second, a gradual age-related shift of the position of isofrequency bands was not seen in any of the nuclei, suggesting that changes in frequency-place code do not occur after 2 weeks postnatally. These results indicate that the rat's auditory brainstem nuclei achieve their adult-like tonotopic organization early on, implying a somewhat different developmental time course than is found in other mammalian species.