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PubMed2002

Synaptic transmission in the auditory brainstem of normal and congenitally deaf mice.

The deafness (dn/dn) mutant mouse provides a valuable model of human congenital deafness. We investigated the properties of synaptic transmission in the anteroventral cochlear nucleus (AVCN) of normal and congenitally deaf dn/dn mice. Excitatory postsynaptic currents (EPSCs) were evoked by focal stimulation of single auditory nerve fibres, and measured by whole-cell recordings from neurones in AVCN slices (mean postnatal age = P13). Absolute amplitudes of both AMPA- and NMDA-mediated components of evoked EPSCs were greater (170 %) in deaf versus control animals. Enhanced transmission in deaf mice was due to a presynaptic mechanism. Variance-mean analysis revealed that the probability of transmitter release was significantly greater in deaf (P(r) = 0.8) versus control animals (P(r) = 0.5). Following high frequency stimulation, deaf mice showed a greater depression of evoked EPSCs, and a significant increase in the frequency of delayed-release (asynchronous) miniature EPSCs (aEPSCs) (deaf 100 Hz vs. control 7 Hz). The acetoxymethyl ester of EGTA (EGTA-AM) blocked the increase in miniature aEPSCs and returned tetanic depression to control values. In deaf mice, reduction of mean P(r) using cadmium caused an expected increase in paired-pulse ratio (PPR). However, in the same cells, a similar reduction in release by EGTA-AM did not result in a change in PPR, demonstrating that a change may occur in P(r) without a concomitant change in PPR. In many respects, transmission in deaf mice was found to be remarkably similar to control mice, implying that many parameters of synaptic transmission develop normally in these animals. The two significant differences (higher P(r) and asynchronous release in deaf mice) could both be reversed by the addition of EGTA-AM, suggesting that endogenous calcium buffering may be impaired or undeveloped in the presynaptic terminals of the auditory nerve in deaf mice.

Animals↗
PubMed1998

Envelope coding in the lateral superior olive. III. Comparison with afferent pathways.

Binaural cues for spatial localization of complex high-frequency sounds are interaural level and time differences (ILDs and ITDs). We previously showed that cells in the lateral superior olive (LSO) are sensitive to ITDs in the envelope of sinusoidally amplitude-modulated (AM) signals up to a modulation frequency of only approximately 800 Hz. To understand the limitations in this ITD-sensitivity, we here compare responses to monaural modulation in LSO and its input pathways, derived from cochlear nucleus and medial nucleus of the trapezoid body. These pathways have marked functional and morphological specializations, suggestive of adaptations for timing. Afferent cell populations were identified on the basis of electrophysiological signatures, and for each population, average firing rate and synchronization to AM tones were compared with auditory-nerve fibers and LSO cells. Except for an increase in modulation gain in some subpopulations, synchronization of LSO afferents was very similar to that in auditory nerve fibers in its dependency on sound pressure level (SPL), modulation depth, and modulation frequency. Distributions of cutoff frequencies of modulation transfer functions were largely coextensive with the distribution in auditory nerve. Group delays, measured from the phase of the response modulation as a function of modulation frequency, showed an orderly dependence on characteristic frequency and cell type and little dependence on SPL. Similar responses were obtained to a modulated broadband carrier. Compared with their afferents, LSO cells synchronized to monaurally modulated stimuli with a higher gain but often over a narrower range of modulation frequencies. Considering the scatter in afferent and LSO cell populations, ipsi- and contralateral responses were well matched in cutoff frequency and magnitude of delays. In contrast to their afferents, LSO cells show a decrease in average firing rate at high modulation frequencies. We conclude that the restricted modulation frequency range over which LSO cells show ITD-sensitivity does not result from loss of envelope information along the afferent pathway but is due to convergence or postsynaptic effects at the level of the LSO. The faithful transmission of envelope phase-locking in LSO afferents is consistent with their physiological and morphological adaptations, but these adaptations are not commensurate with the rather small effects of physiological ITDs reported previously, especially when compared with effects of ILDs. We suggest that these adaptations have evolved to allow a comparison of instantaneous amplitude fluctuations at the two ears rather than to extract interaural timing information per se.

Acoustic Stimulation↗
PubMed2004

Activity-dependent regulation of the potassium channel subunits Kv1.1 and Kv3.1.

Afferent activity, especially in young animals, can have profound influences on postsynaptic neuronal structure, function and metabolic processes. Most studies evaluating activity regulation of cellular components have examined the expression of ubiquitous cellular proteins as opposed to molecules that are specialized in the neurons of interest. Here we consider the regulation of two proteins (voltage-gated potassium channel subunits Kv1.1 and Kv3.1) that auditory brainstem neurons in birds and mammals express at uniquely high levels. Unilateral removal of the avian cochlea leads to rapid and dramatic reduction in the expression of both proteins in the nucleus magnocellularis (NM; a division of the avian cochlear nucleus) neurons as detected by immunocytochemistry. Uniform downregulation of Kv1.1 was reliable by 3 hours after cochlea removal, was sustained through 96 hours, and returned to control levels in the surviving neurons by 2 weeks. The activity-dependent changes in Kv3.1 appear to be bimodal and are more transient, being observed at 3 hours after cochlea removal and recovering to control levels within 24 hours. We also explored the functional properties of Kv1.1 in NM neurons deprived of auditory input for 24 hours by whole-cell recordings. Low-threshold potassium currents in deprived NM neurons were not significantly different from control neurons in their amplitude or sensitivity to dendrotoxin-I, a selective K+ channel antagonist. We conclude that the highly specialized abundant expression of Kv1.1 and 3.1 channel subunits is not permanently regulated by synaptic activity and that changes in overall protein levels do not predict membrane pools.

Animals↗
PubMed1994

Immunohistochemical localization of hyaluronic acid in rat and human brain.

The immunohistochemical localization of hyaluronic acid (HA) was studied in rat and human brain using the monoclonal antibody NDOG1, which specifically recognizes HA. In both rat and human brain, HA-like immunoreactivity formed characteristic coats around neurons in highly selective areas. The staining was abolished by pretreatment of sections with testicular and Streptomyces hyaluronidases, indicating that the staining was specific for HA. In rat brain, positive neurons were located in the cerebral cortex, subiculum, amygdala, thalamic reticular nucleus, nuclei of the inferior colliculus, nuclei of the trapezoid body, and vestibular nuclei. They were also scattered in the hypothalamus, substantia nigra pars reticularis, red nucleus, parabrachial nuclei, brainstem reticular nuclear group, ventral cochlear nucleus, nuclei of lateral lemniscus, and deep cerebellar nuclei. Double immunohistochemical studies showed that many neurons staining for HA were positive for parvalbumin, with minor exceptions in the amygdala and piriform cortex, where some HA-positive neurons were also positive for calbindin-D28k. In the areas studied in human brain, the distribution of HA-positive neurons was virtually identical to that in rat brain. HA-positive neurons were not significantly altered in Alzheimer disease (AD) brain, suggesting that these neurons are resistant to the pathological process of AD.

Aged↗
PubMed1987

Immunoreactivity to calcitonin gene-related peptide in the superior olivary complex and cochlea of cat and rat.

In both cat and rat, the cells of origin, axons, and terminals of the lateral olivocochlear system exhibit immunoreactivity to antisera to calcitonin gene-related peptide (CGRP). In the cat, immunoreactive neurons in the brainstem are located in the hilus of the lateral superior olivary nucleus and around its margins. In the rat, immunoreactive neurons are located within the lateral superior olivary nucleus proper. In both species, immunoreactivity in the cochlear duct is limited to the region beneath the inner hair cells. Immunoreactive axons in the cochlear nucleus could not be traced to their source but may arise as collaterals of the lateral olivocochlear system. No other components of the brainstem auditory system react to any extent with the antisera.

Animals↗
PubMedDate not supplied

Morphometric development of the human fetal auditory system: inferior collicular nucleus.

The development of the human inferior collicular nucleus was studied on serial sections of the brains of 9 fetuses at 12-34 weeks of gestation and an adult of 63 years using an electronic planimeter with a computer. Morphometric analysis of the development of the inferior collicular nucleus showed that its development accelerates after 18 weeks of gestation in terms of the columnar volume and length, size of neurons and circularity ratio. Large-sized neurons 2-3 times the area of small-sized neurons appeared after 18 weeks of gestation. The ratio of large neurons to the total ranged between 3 and 6% in the inferior collicular nucleus. The development of the inferior collicular nucleus was similar to that of the ventral cochlear nucleus and the medial superior olivary nucleus.

Age Factors↗
PubMed2002

The effect of bilateral deafness on excitatory and inhibitory synaptic strength in the inferior colliculus.

The consequences of deafness on the central auditory nervous system have been examined at many levels, from molecular to functional. However, there has never been a direct and selective measurement of excitatory synaptic function following total hearing loss. In the present study, gerbils were deafened at postnatal day 9, an age at which there is no deafferentation-induced cell death of ventral cochlear nucleus neurons. One to five days after bilateral cochlear ablation, the amplitude of evoked excitatory postsynaptic currents (EPSC) was measured with whole-cell voltage-clamp recordings in an inferior colliculus (IC) brain slice preparation in response to electrical stimulation of the ipsilateral lateral lemniscus (LL) or the commissure of the inferior colliculus (CIC). Deafness resulted in larger LL- and CIC-evoked EPSC amplitudes and durations. This result was observed at a depolarized holding potential. In addition, deafness caused a decrease in excitatory neurotransmitter release at the LL pathway, as assessed with a paired-pulse stimulation protocol. In contrast to its effect on excitatory synapses, bilateral cochlear ablation reduced inhibitory synaptic strength in IC neurons. The effects included a postsynaptic decrease in IPSC conductance, a 25-mV depolarization in the IPSC equilibrium potential and a decrease of neurotransmitter release. Thus normal innervation differentially affects excitatory and inhibitory synaptic strength in IC neurons, and these changes may contribute to alterations in auditory coding properties following sensory deprivation.

Animals↗
PubMed2005

Hyperpolarization-activated (I) currents in auditory brainstem neurons of normal and congenitally deaf mice.

We have investigated the membrane properties of brainstem auditory neurons in a mouse model of congenital deafness (dn/dn). Whole-cell recordings were made from visualized neurons in slices of the medial nucleus of the trapezoid body (MNTB) and anteroventral cochlear nucleus (AVCN). We have recently demonstrated that MNTB neurons in deaf mice are more excitable than in normal mice, due in part to a reduced expression of low-threshold potassium currents. In this study, we have examined the contribution of hyperpolarization-activated (Ih) channels to the membrane properties of MNTB and AVCN neurons. Our results show that Ih is larger in MNTB neurons from deaf mice than in normal mice. In contrast, no significant differences were found in Ih or excitability between AVCN bushy cells from dn/dn and normal mice. Experimental evidence and neuronal modelling suggests that, in the MNTB of normal mice, a small contribution of Ih helps to reduce temporal summation of synaptic potentials. A larger Ih in neurons from deaf mice has a much greater effect in reducing temporal summation of synaptic potentials, counteracting to some extent the greater excitability of these cells. Our results provide further insight into the role of activity during development in regulating the membrane and firing properties of central neurons.

Action Potentials↗
PubMed1992

Normal and heat-induced patterns of expression of heme oxygenase-1 (HSP32) in rat brain: hyperthermia causes rapid induction of mRNA and protein.

Most cells possess a variety of mechanisms, such as high levels of glutathione, that guard against cytotoxic free radicals, which are suspected in the etiology of various neurological deficits. Neurons, however, are deficient in this antioxidant source. The list of other potent antioxidants includes the bile pigments biliverdin and bilirubin. Heme oxygenase (HO) isozymes, HO-1 (HSP32) and HO-2, catalyze the rate-limiting step in the only biological pathway by which bile pigments are produced. In this study, heat shock is identified as the only stimulus reported to date that can alter expression in brain HO-1 of protein and mRNA in vivo. Using a HO-1 cDNA probe, we examined the level of HO-1 mRNA in normal rat brain and in brain 1 and 6 h following heat shock. Exposure of male rats to 42 degrees C for 20 min caused a 20-fold increase in brain HO-1 1.8-kb mRNA within 1 h after treatment. Quantification of brain HO-1 protein by HO-1 radioimmunoassay revealed a fourfold increase at 6 h posttreatment. In normal brain, HO-1 protein was sparsely expressed in few select neuronal and nonneuronal cell populations in forebrain, diencephalon, cerebellum, and brainstem regions. Six hours following heat shock, an intense increase in HO-1 protein in glia throughout the brain, ependyma lining the ventricles of the brain, paraventricular nucleus, Purkinje cell layer of the cerebellum, and cochlear nucleus of brainstem was observed. We suggest that increases in HO-1 transcript and protein reflect a means to elevate levels of antioxidants in cells with compromised defense mechanisms caused by stress.

Animals↗
PubMed2001

Tonotopic and somatotopic representation in the nucleus basalis of the barn owl, Tyto alba.

We have investigated the somatosensory and auditory representations in the nucleus basalis of the barn owl. In pigeons and finches, the nucleus basalis contains a representation of the beak and an auditory area. In the barn owl, the nucleus basalis also contains a complete somatotopic map of the head and body (as in the budgerigar), with a tonotopically organized auditory area in close proximity to the representation of the facial ruff and the preaural area. Recordings within and around the nucleus basalis revealed predominantly (about 80%) contralateral responses to somatic stimulation. The somatotopic map was oriented with the head down and rostral. Penetrations revealed an over-representation of the feet in dorsal basalis, followed by the rest of the body and wings more ventrally. Towards more rostral positions in nucleus basalis, responses from the head and beak predominated ventrally. The auditory response area was encountered below the region that responded to stimulation of the facial ruff and preaural flap regions and above a region responsive to beak stimulation. Auditory responses were tonotopically organized, with low best frequencies dorsal. Some penetrations yielded predominantly monaural responses with a fairly broad dynamic range, similar to those recorded from the ventral nucleus of the lateral lemniscus (LLV) and the cochlear nucleus angularis, whereas other penetrations contained predominantly binaural responses sensitive to interaural time differences (ITD). The physiological responses could be predicted on the basis of auditory projections to the nucleus basalis. An injection of biotinylated dextran amine (BDA) in the auditory region of nucleus basalis retrogradely labeled cells in both the caudal and rostral parts of the intermediate lateral lemniscal nucleus (LLIc and LLIr), and a few cells in the anterior part of the dorsal lateral lemniscal nucleus (LLDa, previously known as nucleus ventralis lemnisci lateralis, pars anterior, or VLVa) and in the posterior part of the dorsal lateral lemniscal nucleus (LLDp, previously known as nucleus ventralis lemnisci lateralis, pars posterior, or VLVp). A large injection of cholera toxin B-chain (CTB) into the nucleus basalis also produced dense retrograde labeling of a previously unidentified nucleus on the lateral aspect of the rostral pons, that we here call nucleus pontis externus (PE). An injection of CTB into PE produced dense retrograde labeling of the contralateral dorsal column nuclei and anterograde labeling of the ipsilateral lateral and dorsolateral nucleus basalis. Together these results define major somatosensory and auditory projections to the owl telencephalon that bypass the thalamus.

Afferent Pathways↗
PubMed2003

Prosthetic stimulation of the auditory system with intraneural electrodes.

Prosthetic electrical stimulation of the auditory system is presently accomplished either via scala tympani electrode arrays or via cochlear nucleus surface electrode arrays. Many of the early cochlear implant studies, however, used electrode arrays placed within the auditory nerve itself--either within the modiolus or within the trunk of the nerve. For many reasons, such intraneural electrode arrays were abandoned in favor of intrascalar arrays. There remain, however, several theoretical and practical reasons why intraneural arrays might be advantageous, and recent developments in electrode technology solve many of the problems posed by early attempts at intraneural stimulation. In this article, we review the history and current status of intraneural auditory stimulation, and present some preliminary results of this mode of stimulation in an animal model.

Animals↗
PubMed1997

In situ hybridization histochemical localization of prodynorphin messenger RNA in the central nervous system of the rat.

The distribution of preprodynorphin messenger RNA-containing perikarya in the central nervous system of the rat was determined with in situ hybridization histochemistry using a 35S-labelled complementary RNA probe. All of the regions of the central nervous system reported by other investigators to contain perikarya that synthesize prodynorphin-derived peptides, except the pedunculopontine tegmental nucleus, the accessory trigeminal nucleus, and the ventral nucleus of the trapezoid body, also contained perikarya that synthesize preprodynorphin messenger RNA. However, the olfactory bulb, the anterior olfactory nucleus, the islands of Calleja, the CA1-CA3 fields of the hippocampus, the septohippocampal nucleus, the diagonal band of Broca, the basal and cortical amygdaloid nuclei, the entopeduncular nucleus, the subthalamic nucleus, the superior colliculus, the Edinger-Westphal nucleus, the dentate nucleus, the raphes linearis and pontis, the dorsal cochlear nucleus, the medial vestibular nucleus, the inferior olive, and the dorsal motor nucleus of the vagus nerve also contained preprodynorphin messenger RNA-synthesizing perikarya. These observations suggest that prodynorphin-derived peptides have a much more pervasive role in central nervous system function than previously suspected. However, before the physiological significance of these observations can be judged, it will be necessary to determine whether all of the novel sites of preprodynorphin messenger RNA synthesis are sites of prohormone synthesis and conventional processing.

Animals↗
PubMed1991

Melodic, rhythmic, and timbral perception of adult cochlear implant users.

The purpose of this pilot study was to investigate adult Ineraid and Nucleus cochlear implant (CI) users' perceptual accuracy for melodic and rhythmic patterns, and quality ratings for different musical instruments. Subjects were 18 postlingually deafened adults with CI experience. Evaluative measures included the Primary Measures of Music Audiation (PMMA) and a Musical Instrument Quality Rating. Performance scores on the PMMA were correlated with speech perception measures, music background, and subject characteristics. Results demonstrated a broad range of perceptual accuracy and quality ratings across subjects. On these measures, performance for temporal contrasts was better than for melodic contrasts independent of CI device. Trends in the patterns of correlations between speech and music perception suggest that particular structural elements of music are differentially accessible to cochlear implant users. Additionally, notable qualitative differences for ratings of musical instruments were observed between Nucleus and Ineraid users.

Adult↗
PubMed1982

Functional ontogeny in the central auditory pathway of the Mongolian gerbil. A 2-deoxyglucose study.

The 2-deoxyglucose (2-DG) autoradiographic technique was used to map functional activity in the central auditory system of the mongolian gerbil, throughout the period of functional onset. Uptake of 2-DG during exposure to 105 dB SPL wide band noise (WBN) was compared to silence in adults and in neonates at 12, 14, 16 and 18 days after birth (DAB). At 12 DAB, WBN exposure increased 2-DG uptake relative to silence only in the ventral cochlear nucleus. At 14 DAB, 2-DG uptake increased during WBN in the entire cochlear nuclear complex, superior olivary complex, and ventral nucleus of the lateral lemniscus. These stimulus-evoked increases in 2-DG uptake were at adult levels. However, little or no stimulus-evoked increase was seen in higher auditory nuclei at 14 DAB. By 16 DAB, 2-DG uptake also increased during WBN exposure in the dorsal nucleus of the lateral lemniscus, inferior colliculus and medial geniculate nucleus. By 18 DAB, WBN exposure produced increases in 2-DG uptake of medullary and pontine auditory nuclei which exceeded those seen in adults. At higher levels of the pathway, increases were comparable to those seen in adults. WBN-induced increases in 2-DG uptake observed in the cochlear nuclear and superior olivary complexes of neonates were comparable in all regions at all ages, even at 12 DAB. However, the 2-DG uptake increases observed at 16 and 18 DAB were appreciably greater in those regions of the inferior colliculus and medial geniculate nucleus which respond to high frequencies.

Aging↗
PubMed1990

Migration of neuroblasts by perikaryal translocation: role of cellular elongation and axonal outgrowth in the acoustic nuclei of the chick embryo medulla.

The neuroblasts forming nucleus magnocellularis, the avian homologue of the mammalian ventral cochlear nucleus, migrate by growth and elongation of their leading processes and by perikaryal translocation through these processes from the matrix zone of the rhombic lip to the acoustico-vestibular anlage. Golgi methods were used on staged chick embryos to reconstruct the morphogenetic phases of migration and early differentiation in situ. Fluorescence labeling of the living cells in vitro elucidated the role of axonal growth in the migratory process. In situ, branching cochlear nerve fibers, tipped with growth cones, enter the acoustico-vestibular anlage at E4.5-5.5 before migration of the magnocellularis neuroblasts at E.5.5-6.5. The premigratory neuroblasts in the matrix zone of the rhombic lip resemble primitive epithelial cells, which extend branched, curving processes into a characteristic formation, the rhombic whorl. The leading process of the migrating magnocellularis neuroblasts gives rise to a bifurcating axon at the interface between the matrix and mantle zones. The lateral branch becomes the recurrent ipsilateral collateral; the medial branch crosses the midline, heading toward the contralateral target site in the region of the presumptive nucleus laminaris. The cell bodies of the migratory neuroblasts appear in intermediate locations along the migration route as they translocate radially through their leading processes past the axonal bifurcation and then tangentially and obliquely into the mantle zone. Neuroblasts destined for nucleus laminaris migrate coincidentally with magnocellularis neuroblasts. Nucleus angularis neuroblasts migrate later in development, after E6.5. In vitro, injections of a nontoxic fluorescent dye (diI) were made into explants of the medulla in the region of the contralateral target area at the time of neuroblast migration. DiI retrogradely labeled the cell bodies of premigratory magnocellularis neuroblasts in the matrix zone and of migratory neuroblasts in the mantle zone through their medial, crossing axonal branches. The morphology of the living neuroblasts in the explants resembled that in the Golgi impregnations at the corresponding stages of migration. Anterograde axonal transport also occurred. These results demonstrate migration by perikaryal translocation and early axon extension of a specific group of neuroblasts in the central nervous system. The morphology of the migrating neuroblasts is such that a simple radial arrangement of cellular guides, glial or otherwise, would not account for their configurations. The available evidence supports the proposition that cellular elongation and perikaryal translocation constitute the general mode of neuronal migration in the central nervous system. The early extension of axons into their target sites may play a critical role in migration and early development of specific types of neurons.

Animals↗
PubMed1996

Auditory brain stem response generation by parallel pathways: differential maturation of axonal conduction time and synaptic transmission.

In attempting to correlate developmental anatomical data with electrophysiological data on maturation of the auditory brain stem response (ABR), a model of ABR generation was necessary to match neuroanatomical structures to ABR components. This model has been developed by reviewing quantitative studies of human brain stem nuclei, results of intrasurgical recordings, studies of correlation of pathology with ABR waveform alterations, and findings from direct stimulation of the human cochlear nuclei through a brain stem implant device. Based on this material, it was assumed that waves I and II are generated peripherally in the auditory nerve and that waves III, IV, and V are generated centrally, i.e., by brain stem structures. It was further assumed that wave III is generated by axons emerging from the cochlear nuclei in the ventral acoustic stria and that waves IV and V reflect activity in parallel subpopulations of these ascending axons at a higher brain stem level. Beyond the cochlear nucleus, the largest component of the brain stem auditory pathway consists of axons projecting without interruption from the cochlear nuclei to the contralateral lateral lemniscus and inferior colliculus. In the proposed model of ABR generation, the III-IV interwave interval is assumed to reflect only axonal conduction in this asynaptic pathway. Electrophysiological data from infants indicate that the III-IV interwave interval becomes adult-like by the time of term birth. The second largest component of the brain stem auditory pathway is the bilateral projection through the medial olivary nucleus. The model assumes that activity in this monosynaptic pathway, consisting of axonal conduction time plus one synaptic delay, is reflected in the III-V interwave interval. If both of the preceding assumptions are true, the IV-V interwave interval represents the difference between the two pathways, i.e., the time of transmission across one synapse. The electrophysiological ABR data indicates that the IV-V interval does not mature until one year of age. It is also possible to apply this model to the peripherally generated portion of the ABR. The I-II interwave interval, assumed to solely represent conduction in VIIIth nerve axons, is adult-like before the time of term birth. The II-III interval, presumed to contain a synapse in the cochlear nuclear complex, does not reach an adult level until between 1 and 2 yr postnatal age.

Axons↗
PubMed2004

Localization of myosin phosphatase target subunit 1 in rat brain and in primary cultures of neuronal cells.

Myosin phosphatase (PP1M) is composed of the delta isoform of the PP1 catalytic subunit (PP1cdelta), the myosin phosphatase target subunit (MYPT), and a 20 kDa subunit. Western blots detected higher amounts of the MYPT1 isoform compared to MYPT2 in whole brain extracts. The localization of MYPT1 was studied in rat brain and in primary cell cultures of neurons using specific antibodies. Analysis of lysates of brain regions for MYPT1 and PP1M by Western blots using anti-MYPT1 antibodies and by phosphatase assays with myosin as substrate suggested a ubiquitous distribution. Immunohistochemistry of tissue sections revealed that MYPT1 was distributed in all areas of the brain, with staining observed in many different cell types. Depending on the method used for fixation, the MYPT1 appeared with varying intensity in nuclei, in nucleoli, and in the cytoplasm. In primary hippocampal cultures, MYPT1 was identified by confocal microscopy in the cytoplasm and in the nucleus, whereas a predominantly cytoplasmic localization was found in cochlear nucleus cells. In cultured cells, MYPT1 and PP1cdelta colocalized with synaptophysin. PP1M activity was high in synaptosomes isolated from the cerebral cortex, but was relatively low in the postsynaptic densities. The interaction of MYPT1 with synaptophysin and with known partners (Rho-kinase, PP1cdelta) in brain extracts was shown by immunoprecipitation with anti-MYPT1. Pull-down assays from synaptosomes, using GST-MYPT1, also confirmed these interactions. In conclusion, the widespread cellular and subcellular localization of MYPT1 implies that PP1M may play an important role in the dephosphorylation of key regulatory proteins in neuronal cells.

Animals↗
PubMed1993

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↗