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Protein kinase C in central auditory pathways of the rat.

Protein kinase C is an important intracellular signaling molecule. Many of its ten isoforms are highly expressed in brain, and protein kinase C has been implicated in the regulation of the activity of receptors of several major neurotransmitters, including glutamate, acetylcholine, glycine, and gamma-aminobutyric acid. These neurotransmitters and their receptors are present in central auditory pathways, suggesting their role in auditory signal processing. Although they may be important modulators of the function of these neurotransmitter receptors, the distribution of protein kinase C isoforms in central auditory systems has not been well characterized. By using immunocytochemistry with specific antibodies, we studied the distribution of immunoreactivity of four isoforms of protein kinase C, betaI, betaII, gamma, and gamma, in central auditory systems of rat brain. Each of these protein kinase C isoforms was found to have a unique distribution in the auditory brainstem and cortex, supporting a role for these isoforms of protein kinase C in different aspects of auditory sensory processing.

Animals↗

c-Fos expression in the auditory pathways related to the significance of acoustic signals in rats performing a sensory-motor task.

Neuronal activity was established in the auditory pathways in relation to behavioural response and cognitive information processing during a sensory-motor acoustic learning. Rats were trained in three consecutive phases. The first phase was an association between an auditory stimulus and a food reward; the second phase a simple discrimination between two sounds of different frequency components, and the third phase a more complex discrimination involving both spectral and spatial sound dimensions. Auditory stimuli were bursts of complex sounds lasting 500 ms. Neuronal activity related to the behaviourally relevant stimuli was established in 20 "learning" rats undergoing this protocol, which were progressively sacrificed at the beginning, middle and end of each phase. For comparison, activity was also established in four "control" rats exposed to the same stimuli delivered pseudo-randomly, thus carrying no behavioural meaning. Neuronal activity was assessed immunocytochemically using the functional marker Fos. To establish a baseline, two rats were unexposed to controlled acoustic stimulation ("unstimulated" rats). In the superior olivary complex (SOC), inferior colliculus (IC) and medial geniculate body (MGB), the number of Fos-like immunopositive cells was comparable in "learning" and "control" animals, but higher than in the "unstimulated" rats. In the auditory cortex (AC), most prominently in the secondary area Te2, the number of Fos-like positive cells differed between "learning" and "control" rats, suggesting that the auditory cortical areas may be involved in the encoding of the behavioural significance of the acoustic stimuli.

Acoustic Stimulation↗

Demonstration of prosthetic activation of central auditory pathways using [14C]-2-deoxyglucose.

The cochlear prosthesis is not applicable to patients who lack an implantable cochlea or an intact vestibulocochlear nerve. Direct electrical stimulation of the cochlear nucleus (CN) of the brain stem might provide a method for auditory rehabilitation of these patients. A penetrating CN electrode has been developed and tissue tolerance to this device demonstrated. This study was undertaken to evaluate metabolic activation of central nervous system (CNS) auditory tracts produced by such implants. Regional cerebral glucose use resulting from CN stimulation was estimated in a series of chronically implanted guinea pigs with the use of [14C]-2-deoxyglucose (2-DG). Enhanced 2-DG uptake was observed in structures of the auditory tract. The activation of central auditory structures achieved with CN stimulation was similar to that produced by acoustic stimulation and by electrical stimulation of the modiolar portion of the auditory nerve in control groups. An interesting banding pattern was observed in the inferior colliculus following CN stimulation, as previously described with acoustic stimulation. This study demonstrates that functional metabolic activation of central auditory pathways can be achieved with a penetrating CNS auditory prosthesis.

Animals↗

Auditory pathways to the hypothalamus in ranid frogs.

Three multisynaptic pathways from the midbrain auditory center (torus semicircularis) of the bullfrog, Rana catesbeiana, to the infundibular hypothalamus were found using the axonal tracer wheat germ agglutinin-horseradish peroxidase. Toral neurons project to the secondary visceral nucleus of the isthmus and to the central and anterior thalamic nuclei of the dorsal thalamus. All 3 of these nuclei project to the infundibular hypothalamus. These findings indicate multiple connections between two centers presumed important for reproductive behavior in frogs, a midbrain sensory region processing acoustic communication signals and a hypothalamic endocrine control area regulating gonadotropin and gonadal steroid secretion.

Animals↗

Auditory pathways of caudal telencephalon and their relation to the song system of adult male zebra finches.

Auditory information is critical for vocal imitation and other elements of social life in song birds. In zebra finches, neural centers that are necessary for the acquisition and production of learned vocalizations are known, and they all respond to acoustic stimulation. However, the circuits by which conspecific auditory signals are perceived, processed, and stored in long-term memory have not been well documented. In particular, no evidence exists of direct connections between auditory and vocal motor pathways, and two newly identified centers for auditory processing, caudomedial neostriatum (Ncm) and caudomedial hyperstriatum ventrale (cmHV), have no documented place among known auditory circuits. Our goal was to describe anatomically the auditory pathways in adult zebra finch males and, specifically, to show the projections by which Ncm and vocal motor centers may receive auditory input. By using injections of different kinds of neuroanatomical tracers (biotinylated dextran amines, rhodamine-linked dextran amines, biocytin, fluorogold, and rhodamine-linked latex beads), we have shown that, as in other avian groups, the neostriatal field L complex in caudal telencephalon is the primary forebrain relay for pathways originating in the auditory thalamus, i.e., the nucleus ovoidalis complex (Ov). In addition, Ncm and cmHV also receive input from the Ov complex. Ov has been broken down into two parts, the Ov "core" and "shell," which project in parallel to different targets in the caudal telencephalon. Parts of the field L complex are connected among themselves and to Ncm, cmHV, and caudolateral Hv (clHV) through a complex web of largely reciprocal pathways. In addition, clHV and parts of the field L complex project strongly to the "shelf" of neostriatum underneath the song control nucleus high vocal center (HVC) and to the "cup" of archistriatum rostrodorsal to another song-control nucleus, the robust nucleus of the archistriatum (RA). We have documented two points at which the vocal motor pathway may pick up auditory signals: the HVC-shelf interface and a projection from clHV to the nucleus interfacialis (NIf), which projects to HVC. These data represent the most complete survey to date of auditory pathways in the adult male zebra finch brain, and of their projections to motor stations of the song system.

Acoustic Stimulation↗

Auditory pathway plasticity in adult humans after unilateral idiopathic sudden sensorineural hearing loss.

We recorded auditory evoked magnetic fields from 8 patients with unilateral, idiopathic, sudden, sensorineural hearing loss and from 8 healthy controls, using a 122-channel whole-scalp neuromagnetometer. The stimuli were 50-ms l-kHz tone bursts, delivered to the healthy ear at interstimulus intervals (ISIs) of 1, 2, 4, 8, and 16 s. On average, as in normal-hearing controls, the dipole moments and the latencies of N100m, the 100-ms response, increased as a function of ISI over both hemispheres to left- and right-ear stimulation. Four patients had shorter response latencies and 4 had stronger dipole moments over the hemisphere ipsilateral to the stimulation. In 3 patients, one additional source was observed over the anterolateral right hemisphere and another near head midline. These findings suggest that unilateral sensorineural hearing loss may modify information processing in the central auditory pathways.

Acoustic Stimulation↗

On the existence in human auditory pathways of channels selectively tuned to the modulation present in frequency-modulated tones.

1. The sensitivity of detecting modulation in a test tone sinusoidally frequency-modulated at a rate varphi(test) is diminished after exposure to a conditioning tone more deeply frequency-modulated at a rate varphi(cond) provided that varphi(cond) is not very different from varphi(test), the sound amplitude being kept constant for each tone at a comfortable hearing level 40-45 dB above threshold.2. When varphi(cond) = varphi(test) the frequency deviation in the modulated test tone must be increased to about three times the unconditioned threshold magnitude to be detectable immediately after exposure to the conditioning tone. Detection sensitivity returns to normal in about one minute.3. At low modulation frequencies the conditioning effects are tuned, being much diminished when varphi(cond) differs from varphi(test) by a few cycles per second.4. Comparing monaural with contra-aural conditioning demonstrates a considerable interaural transfer of about 60-80% of the effect, indicating that the conditioning and its selectivity are predominantly central phenomena.5. The magnitude of the deterioration in detection sensitivity after conditioning is about 3 x at modulation frequencies between about 3/sec and 30/sec. It diminishes at lower and higher modulation frequencies and is effectively absent at 100/sec modulation. The bandwidth of the effect increases from a few cycles per second at the lower end of this range, to some tens of cycles per second at the upper end.6. For the same modulation frequency, the conditioning is relatively insensitive to the mean ;carrier' audiofrequency, f(0). The band width in terms of carrier frequency is at least as wide as ;critical bands'. With a test signal f(0) = 250 Hz, varphi(test) = 8/sec, conditioning is still appreciable for a conditioning tone of varphi(cond) = 8/sec but centred upon f(0) = 150 Hz or = 350 Hz. Conditioning is thus not explicable in terms of coincidences between particular spectral components in the conditioning and test tones.7. Whereas the sensitivity of detecting 8/sec amplitude modulation in a tone is conditioned by prior exposure to either amplitude- or frequency-modulated tones, in contrast the detectability of 8/sec frequency-modulated signals is conditioned only by prior exposure to frequency-modulated tones and not by amplitude-modulated conditioning tones. This underlines the special place of frequency modulation in human audition and emphasizes that the operative stimulus cannot be some aspect common to amplitude modulation and frequency modulation, like identical periodicity or coincident positioning of bands in the integrated spectra of the tones, but points to the instantaneous frequency-modulated wave form as the adequate stimulus.8. These findings strongly suggest that the human auditory pathways contain ;channels' in their organization which determine a final response selectively tuned to particular frequency-modulations. Periodicity coding alone cannot adequately explain this effect which may well only be understood in terms of a ;place' theory of frequency selectivity.9. This organization is well suited to subserve the recognition of frequency-modulation patterns in acoustic signals rather independently of the mean audiofrequency that carries the frequency modulation.

Acoustic Stimulation↗

Brainstem auditory pathway degeneration associated with chronic cochlear implants in the monkey.

The form and pattern of first-order and transsynaptic degeneration in the central auditory pathway was studied in monkeys following inner ear stimulation by a cochlear implant. Multielectrode, scala tympani, and modiolar systems were implanted; in some cases, neomycin was perfused into the cochlea to destroy the organ of Corti at the time of implantation. The monkeys were maintained chronically for 5 to 120 weeks, then the cochleas and brainstems were examined histologically. The extent of spiral ganglion cell loss across animals showed variability, reflecting the different procedures and devices used. The degree and distribution of spiral ganglion cell loss was related to the degree and distribution of neural degeneration seen in the cochlear nucleus in all cases. Peripheral damage progressed toward the cochlear apex as survival time increased, and this progression was reflected in the cochlear nucleus by a ventrolateral shift in the locus of degeneration over time. In addition, evidence for transneuronal degeneration was seen at the superior olive, the lateral lemniscus and the inferior colliculus. Our findings indicate that several factors inherent in the use of a cochlear prosthesis, i.e., insertion trauma, host reaction, and/or electrical stimulation, may be associated with a long-term, continuing process of central degeneration visible at several levels of the auditory system.

Animals↗

Tonotopic organization in the central auditory pathway of the Mongolian gerbil: a 2-deoxyglucose study.

The uptake of 2-deoxyglucose (2-DG) was employed to map functional activation of the central auditory pathway in the mongolian gerbil, during 85 dB SPL stimulation with pure tonal stimuli at frequencies of 0.75, 3.0, or 12.0 kHz. Pure tones produced foci of very high 2-DG uptake, when compared to adjacent tissue, in the cochlear nucleus, superior olivary complex, and inferior colliculus. Less distinct areas of elevated 2-DG uptake were seen in the dorsal and ventral nuclei of the lateral lemniscus, medial geniculate nucleus, and auditory cortex. Little or no change in the distribution of 2-DG uptake was noted in the nucleus of the trapezoid body. The location of discrete regions of relatively high 2-DG uptake varied systematically with stimulus frequency. The tonotopic organization demonstrated by 2-DG mapping agreed well with the results of previous electrophysiological studies for most structures. However, in the inferior colliculus, stimulus-evoked increases in 2-DG uptake were found to occur in a fixed pattern of three to four bands across the central nucleus, which did not correspond to any previously reported anatomical or physiological organization. Pure tonal stimuli activated discrete portions of this banding pattern. Also, a small area at the ventromedial edge of the colliculus was more broadly tuned than other regions of the nucleus. It is concluded that 2-DG uptake is well suited to the investigation of tonotopic organization. This technique reveals patterns of activation which have not been observed with other methodologies.

Animals↗

Transient CD15 expression reflects stages of differentiation and maturation in the human subcortical central auditory pathway.

The expression of the terminal saccharide determinant CD15 (3[a1-3]-fucosyl-N-acetyl-lactosamine) was evaluated in the central auditory system of the human developing brain by using monoclonal antibodies against this epitope. CD15 immunoreactivity was first observed in the ventral cochlear nucleus at 10 weeks of gestation, whereas the dorsal cochlear nucleus became positive from 13 weeks of gestation. In both nuclei, the intensity of immunoreactivity increased until 16 weeks of gestation and lasted until 25 weeks of gestation. In the inferior colliculi, CD15 was poorly expressed in the central nucleus from 13 to 23 weeks of gestation and later with moderate levels until birth. Within the medial geniculate nucleus, a biphasic pattern of expression was observed with peaks around 14-17 and 21-24 weeks of gestation. Heterogeneous expression in the medial geniculate nucleus, which was associated either with neurons or the neuropil, allowed distinction of subnuclei. In many of the auditory pathway structures (e.g., ventral cochlear nucleus and central nucleus of the inferior colliculus), a heterogeneous pattern of CD15 expression in the form of repeating parallel bands, possibly related to tonotopic organization, became transiently apparent around 23 weeks of gestation, whereas in the magnocellular part of the medial geniculate nucleus, a striking modular or compartmental arrangement of immunoreactive structures (which could also be associated with tonotopic organization) was also noted at about 23 weeks of gestation. We propose that the initiation of CD15 expression in each nucleus heralds the appearance of functional contacts and that high levels of neuropil labeling are related to the formation of nonstabilized synaptic contacts. Thus, transient CD15 expression in the central auditory system is possibly correlated with phases of functional plasticity in this pathway.

Aging↗

Regeneration and recovery of the hearing function of the central auditory pathway by transplants of embryonic brain tissue in adult rats.

The present study is the first report of successful regeneration and recovery of hearing function of the central auditory pathway after transection in the adult rat. The ventral cochlear tract in the brain stem to pons was transected on one side in adult rats. Tissue from embryos (E14 to E16) was used to cover the lesion site. In 30% of the rats examined, the axons regrew beyond the transected site and regenerated into the denervated side and terminated at the normal targets. The hearing function of rats was elucidated by recording the auditory brain stem response (ABR). Rats with successful regeneration showed nearly normal ABR. In rats receiving simple transection without covering embryonic tissue, there was no regeneration and hearing function did not recover. Thus, the present findings contradict the widely held view that the adult mammalian central auditory system cannot be restored following damage.

Animals↗

Anatomy of the auditory pathways, with emphasis on the brain stem.

The principal auditory leading to the cerebral cortex and therewith to conscious perception passes from the cochlea, via the cochlear nuclei, the inferior colliculus and the medial geniculate body to the contralateral auditory cortex in the temporal lobe. All components of this pathway are cochleotopically organized. The fibre stream leading from the cochlear nuclei to the contralateral inferior colliculus consists of both direct and multisynaptic components. The latter are interrupted one or more times in the superior olivary complex and/or the nuclei of the lateral lemniscus, cell assemblies that lie embedded into the main ascending fibre stream. The auditory cortex receives not only impulses from the contralateral cochlea, but also from the ipsilateral cochlea. The ipsilateral projection reaches the ipsilateral inferior colliculus after a synaptic interruption in the ipsilateral superior olivary complex. Fibres conveying impulses from the contralateral side back to the ipsilateral side are probably also involved. The auditory system of the brain stem is characterized by the presence of several well-developed commissures. Most of these contain, in addition to decussating components, true commissural fibres. The various auditory centres in the brain stem are not only way stations in the ascending auditory pathways, but also serve as relays in descending auditory projections. Most important among the latter is the cortico-cochlear projection which is synaptically interrupted in the inferior colliculus and the periolivary nuclei. The final link in this descending projection is formed by the bundle of Rasmussen, the fibres of which leave the central nervous system and innervate the inner and outer hair cells in the organ of Corti. The pathways for the auditory startle response, the auditory orientation reflex and the stapedius and tensor tympani reflexes are briefly described.

Auditory Pathways↗

Abrupt unilateral deafness modifies function of human auditory pathways.

We studied nine patients with unilateral abrupt deafness caused by acoustic neuroma surgery. Cortical responses to tones delivered to the intact ear were recorded postoperatively with a 122-channel whole-scalp neuromagnetometer. In three patients, followed for 12 months with 2-4 measurements, evoked responses originating in the auditory cortices were weak and delayed one month after the operation in both hemispheres. During the follow-up, the amplitudes reached the control level. No response abnormalities were found in patients who were studied 1.5-4.5 years after the operation. Our findings suggest that abrupt unilateral deafness causes immediate changes in the function of auditory pathways of adult humans and that reorganization takes place within 1 year.

Adolescent↗

Hearing loss in multiple sclerosis: localization of the auditory pathway lesion according to electrocochleographic findings.

Multiple sclerosis is known to affect the myelin of the auditory pathway resulting in acute hearing loss. Two cases of sudden deafness due to multiple sclerosis have been evaluated by conventional audiometry, brainstem auditory evoked response audiometry and transtympanic electrocochleography. The abnormalities of the compound action potential in both patients (enhanced latency, abnormal adaptation using fast stimulus rate) and the normal receptor potentials (cochlear microphonic, summating potential), as well as the absence of brainstem responses suggest a disturbance of synchronization at the level of the first auditory neurone. The electrocochleography provides valuable information for the topodiagnosis of this and other neural hearing losses, especially in the absence of reliable brainstem responses.

Adult↗

The effect of 1,3-dinitrobenzene on the functioning of the auditory pathway in the rat.

1,3-Dinitrobenzene (DNB) has previously been shown to be neuropathic, causing gliovascular lesioning in the rat brainstem, with the nuclei of the auditory pathway being particularly affected. Lesion severity was shown to be dependent on functional activity, which could be markedly decreased within one pathway by monaurally reducing sensory input. The aim of this study was to characterise the changes in electrophysiological and vascular function associated with this asymmetric lesioning. Depth electrodes located in the inferior colliculi were used to measure wave II and IV of the auditory evoked response (AER) and collicular blood flow. These were measured up to eight days after DNB exposure in rats, in which preexisting reduction in sensory input in one ear was achieved by tympanic membrane rupture. Significant increases of between 14-27 dB were seen in the mean stimulus level required to generate a 50% isoamplitude response for wave IV in the intact (ie vulnerable) pathway over days 1-8 post DNB. No significant changes in this response for the other AER waves were seen over the same recording period. Significant increases in blood flow were seen in the inferior colliculi up to 24 hours after the final dose of DNB. Differences in increased flow between the colliculi were also highly significant, with peak increases of 200% and 80% seen in the intact and protected sides respectively. This difference shows that DNB enhanced blood flow appears to reflect the severity of the DNB induced functional deficit. In both cases, disturbance to normal glial function in maintaining K+ homeostasis, may underlie the neurophysiological deficit and the increase in blood flow seen at the level of the inferior colliculi. These asymmetric functional changes were also parallelled by the differential lesion severity between the protected and unprotected pathways. Hence, protection against DNB glial lesion severity by reduction in sensory input, and consequently metabolic demand, is paralleled by the early vascular response and functional neuronal deficit seen over the eight day post DNB recording period.

Acoustic Stimulation↗

Glycine-like immunoreactivity in the rat auditory pathway.

From neurophysiological and biochemical studies it has been suggested that glycine can function as a major inhibitory neurotransmitter in the central nervous system of mammals. In the present study, anti-glycine antiserum was obtained from rabbits immunized with glycine conjugated to rabbit serum albumin via glutaraldehyde and purified by affinity chromatography. The antibody thus obtained was found specific for glycine as determined by an enzyme immunoassay system. The immunocytochemical distribution of glycine in the auditory tract and internal ear was investigated with the antibody. In the central auditory pathway, glycine-like immunoreactivity was mainly located in the ventral and dorsal cochlear nuclei, trapezoid body, lateral lemniscus and inferior colliculus. In the labyrinth, immunoreactivity was detected in the vestibular ganglion and the supporting cells of the crista ampullaris and the organ of Corti, but not in the spiral ganglion. These findings suggest an important role of glycine in the auditory and vestibular pathways.

Animals↗