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PubMed2001

Real time mapping of rat midbrain neural circuitry using auditory evoked potentials.

Auditory evoked potentials were recorded in 360 homogeneously spaced sites, in a volume encapsulating the lateral lemniscus-inferior colliculus transition of anaesthetized rats, in order to calculate the electric field vector distribution with each moment in time referenced to the onset of sound presentation. Software, to conduct calculations and graphical representation, and hardware, to minimize neural damage upon recording, were developed in our laboratory. Our results indicate a smooth transition of both amplitude and direction of vectors, suggestive of sequentially activated sites with outward and inward ionic currents coherent with what is known of this part of the primary auditory pathway. That is, anatomical sites (neural generators) and latency for activation matches previous research of the auditory pathway, while adding a real time perspective to the anatomical substrates recruited during the auditory evoked response. An algorithm for calculating the divergent of the vector field, an estimate of the current source density inside the three-dimensional control volume, was used to infer the possible current sinks and sources generating the field potentials. This technique allowed a clear visualization of two distinct discharges arising from the lateral lemniscus towards the inferior colliculus, thus recording signal propagation, as a movie file, with 0.06 ms time resolution.

Algorithms↗
PubMed1990

[Presbyacusis].

Presbyacusis is senescence in the auditory system. Currently, the etiology of presbyacusis is thought to be mainly due to environmental noise and arterial sclerosis. Cumulative effects of social noise influence the auditory function gradually. Sclerotic change of arteries in the brain occurs along the total auditory pathway. Histopathological findings reveal characteristic changes in all parts of the auditory pathway in elderly persons. Alterations include thickening of the ear drum, sclerotic change of the ossicles joint, decreasing number of hair cells, degeneration of the eighth nerve and of the neurons in the auditory center. Pure tone audiograms show gradually progressive sensorineural hearing loss at high frequencies due to lesions characteristic of senescence. During the 30's the threshold at 8 KHz increases a little, but in the 60's the pure tone threshold increases over all frequencies. The maximum speech discrimination parallels the drop in the pure tone threshold level. In contrast to the normal speech discrimination score, the speech discrimination score using frequency distorted words is very low in senile persons. There is no known therapy for presbyacusis. Hearing aids compensate hearing impairment to some extent, but patient's adaptation to hearing aids is undetermined.

Aged↗
PubMed1982

Startle habituation in rats after lesions in the brachium of the inferior colliculus.

Bilateral interruption of the primary ascending auditory pathway at the level of the brachium of the inferior colliculus (BIC) did not affect short- or long-term habituation of the startle response provoked by auditory stimuli. Animals with BIC lesions and control animals exhibited comparable habituation following manipulations of stimulus intensity, inter-stimulus interval, and intensity of background noise, although animals with lesions in the BIC were more responsive than controls to auditory stimuli and to tactile stimuli. The integrity of the primary auditory pathway above the inferior colliculus is not necessary for short- or long-term habituation of the acoustic startle response.

Acoustic Stimulation↗
PubMed2005

Sounds do-able: auditory-motor transformations and the posterior temporal plane.

Accumulating evidence in humans and non-human primates implicates the posterior superior temporal plane (STP) in the processing of both auditory spatial information and vocal sounds. Such evidence is difficult to reconcile with existing accounts of the primate auditory brain. We propose that the posteromedial STP generates sequenced auditory representations by matching incoming auditory information with stored templates. These sequenced auditory representations are subsequently used to constrain motor responses. We argue for a re-assessment of the much-debated dorsal auditory pathway in terms of its generic behavioral role as an auditory "do" pathway.

Animal Communication↗
PubMed2001

Neural recognition molecule NB-2 of the contactin/F3 subgroup in rat: Specificity in neurite outgrowth-promoting activity and restricted expression in the brain regions.

NB-2, a neural cell recognition molecule of the contactin/F3 subgroup, promoted neurite outgrowth of the cerebral cortical neurons but not the hippocampal neurons. NB-2 in rat became apparent after birth at protein level, reaching a maximum at postnatal day 14 in the cerebrum and postnatal day 3 in the cerebellum. NB-2 in the cerebellum declined abruptly thereafter. In situ hybridization demonstrated that NB-2 mRNA was highly expressed in regions implicated in the central auditory pathway, including the cochlear nuclei, superior olive, inferior colliculi, medial geniculate nuclei, and auditory cortex. In addition, a high level of NB-2 expression was observed in the accessory olfactory bulb, thalamic nuclei, facial nucleus, and inferior olive. By immunohistochemistry, intense immunoreactivity against NB-2 was also detected in the auditory pathway. Thus, NB-2 is expressed in highly restricted brain regions, including the auditory system, suggesting that it plays specific roles in the development and/or maturation of the regions.

Aging↗
PubMed1995

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↗
PubMed2003

The cumulative effect of high click rate on monaural and binaural processing in the human auditory brainstem.

OBJECTIVE: The objective of the present study was to compare the effects of high stimulus rate and click position in the train on monaurally and binaurally evoked activities in the human auditory brainstem and suggest their possible physiological mechanism. METHODS: Auditory brainstem evoked potentials (ABEPs) were recorded from 15 normally and symmetrically hearing adults from 3 channels, in response to 50dB nHL, alternating polarity clicks, presented at a rate of 21/s as well as separately to each click in a train of 10 with an interstimulus interval of 11ms. Click trains were presented at a rate of 5.13/s. The binaural interaction components (BICs) of ABEPs were derived by subtracting the response to binaural clicks from the algebraic sum of monaural responses. Single, centrally located equivalent dipoles were estimated as concise measures of the surface-summated activity of ABEPs and BICs generators. RESULTS: A significant effect of click position in the train on equivalent dipole latency of ABEP component V and on equivalent dipole magnitude of III were found. Latency was prolonged and amplitude was increased the later the click's position in the train. A significant effect of click position in the train on equivalent dipole latencies of all components of BICs was found. Latencies were prolonged if the click's position occurred later in the train, with most of the latency shift achieved by the third click in the train for the first major BIC and by the seventh click for other BIC components. No significant effects on equivalent dipole magnitudes of BICs were found. No significant effect of click position in the train on orientation of any of the equivalent dipoles of ABEP or BIC was found. CONCLUSIONS: The progressive prolongation of latency of ABEP and BIC components with advancing position in the train may be attributed to cumulatively decreased synaptic efficacy at high stimulus rates, resulting in prolonged synaptic delays along the auditory pathway. The paradoxic enhancement of ABEP dipole III magnitude with advancing click position in the train may reflect higher sensitivity of inhibitory brainstem neurons to increased stimulus rate, resulting in disinhibition. The absence of significant effects on BIC dipole magnitudes may reflect the amplifying effect of divergence in the ascending auditory pathway, as has been observed for the monaurally evoked ABEP components from the upper pons.

Acoustic Stimulation↗
PubMed2000

[Using the Mongolian gerbil (Meriones unguiculatus) as an animal model in ontogenetic cochlear implant research].

One of the problems when providing prelingually deafened children with a cochlear implant is to find the optimal moment for the implantation in order to make optimal use of the sensitive phase in the maturation of the auditory system and to achieve the maximum improvement of hearing. Ontogenetic questions can be investigated in animal experiments under controlled conditions. In the present study an animal model (gerbil, Meriones unguiculatus) was established to simulate the situation of prelingually deafened children and to examine the influence of chronic electrostimulation on the development of the auditory pathway. We used species specific sounds for chronic stimulation to simulate significance of human language in our animal modell. A daily two-hour electrostimulation during the ontogenesis of early deafened animals lead to a partial compensation of the functional degeneration of the auditory pathway, which can be observed in totally deafened animals. This animal model provides an elaborate test design which can be used in CI research for the investigation of numerous problems.

Animals↗
PubMed2004

An animal model for cochlear implants.

OBJECTIVE: To test the feasibility of using the deaf white cat model of early-onset deafness. We studied the neuronal effects of prosthetic intervention with a clinical, "off-the-shelf" multichannel cochlear implant. METHODS: We placed cochlear implants in 5 deaf white kittens at age 12 and 24 weeks. The devices were activated and stimulated in the laboratory using a clinical speech processor programmed with a high-resolution continuous interleaved sampling (CIS) strategy for 8 to 24 weeks. Stimulus parameters were guided by electrically evoked brainstem responses and intracochlear-evoked potentials. Kittens were assessed with respect to their tolerance and general behavior in response to speech, music, and environmental sounds. RESULTS: Surgical complications were minimal, and kittens tolerated the experimental procedures well. Subjects were able to detect and respond to a specific sound played from a computer speaker. Electrophysiologic responses were reliably attainable and showed consistency with observed behavioral responses to sound. This experimental paradigm, using clinical devices, can be used in a practical research setting in cats. CONCLUSIONS: Deafness and other variations in neural activity result in many distinct changes to the central auditory pathways. Animal models will facilitate assessment of the reversibility of deafness-associated changes at the level of the neuron and its connections. Our observations of the feasibility of using clinical devices in animal models will enable us to simulate clinical conditions in addressing questions about the effects of "replacement" activity on the structure and function within the central auditory pathways in deafness.

Animals↗
PubMed1996

The effects of early and late preterm birth on brainstem and middle-latency auditory evoked responses in children with normal neurodevelopment.

In preterm and term infants, brainstem and middle latency auditory evoked responses (ABR and MLR) were obtained at 40 and 52 weeks conceptional age (CA) and at 5 years of age. A neurological and neuropsychological evaluation was performed at 5 years of age. To study the effect of preterm birth on the maturation of the ABR and MLR, the preterm infants were divided into early and late preterm groups. Only children with a normal neurodevelopmental outcome at 5 years of age were entered into the study. For ABR, the late preterm group showed significantly longer mean latencies IIc, III, V, and Vc when compared with the term group at 52 weeks CA. There was a trend to longer ABR latencies I in the early preterm group compared with the term group. At 52 weeks CA, the late preterm group showed longer mean interpeak latencies III-I and V-I when compared with the term as well as the early preterm group. At 5 years, the late preterm group showed significantly longer mean ABR latencies IIc and III when compared to the early preterm group. For MLR, the early preterm group showed significantly longer mean latencies of MLR component PO when compared with the term group at 40 weeks CA. At 52 weeks, the late preterm group also had longer mean MLR latencies P0 than the term group. At 5 years of age, the term group showed higher mean peak-to-peak amplitudes Na-P0 than the early as well as the late preterm group. To a large extent, the ABR results support the hypothesis that middle ear effusions in combination with retarded myelination of the central auditory pathway are responsible for the ABR differences found between term and preterm infants with a normal neurodevelopmental outcome at 5 years of age. The longer latencies and interpeak latencies found in late preterm infants when compared with early preterm infants might be explained by an augmented vulnerability of the auditory pathway between 30 and 34 weeks CA. The MLR differences found between term and preterm infants might be explained by a difference in the maturation of primary and nonprimary MLR components.

Auditory Cortex↗
PubMed1987

Tolrestat, an aldose reductase inhibitor, prevents nerve dysfunction in conscious diabetic rats.

The effect of 4 wk of streptozocin (STZ)-induced diabetes on the transmission time of the auditory-evoked brain stem response (ABR) was examined in conscious male Sprague-Dawley rats. Distal nerve transmission time of the auditory pathway (latency of peak II), which includes conduction along the 8th cranial nerve, increased in diabetic rats (n = 9) relative to nondiabetic rats (n = 17). The difference in peak II latency between diabetic and control rats was significant beginning 2 wk after the induction of diabetes (P less than .05). In contrast, 4 wk of STZ-induced diabetes had no effect on the central transmission time of the auditory pathway (interpeak latency between peaks II and IV). Oral administration of tolrestat, a structurally novel aldose reductase inhibitor (n = 8; 20 mg/kg twice daily 1 wk before and 4 wk after STZ injection), prevented the diabetes-induced increase in distal nerve transmission time. These findings indicate that experimentally induced diabetes can result in a nerve dysfunction as measured by the increased latencies of the early components of the ABR. Furthermore, because tolrestat prevents these changes in the ABR, aldose reductase and the polyol pathway are implicated in this neuropathy.

Aldehyde Reductase↗
PubMed2000

Contrasting molecular composition and channel properties of AMPA receptors on chick auditory and brainstem motor neurons.

1. Neurons in the brainstem auditory pathway exhibit a number of specializations for transmitting signals reliably at high rates, notably synaptic AMPA receptors with very rapid kinetics. Previous work has not revealed a common structural pattern shared by the AMPA receptors of auditory neurons that could account for their distinct functional properties. 2. We have used whole-cell patch-clamp recordings, mRNA analysis, immunofluorescence, Western blots and agonist-evoked cobalt uptake to compare AMPA receptors on the first-, second- and third-order neurons in the chick ascending auditory pathway with those on brainstem motor neurons of the glossopharyngeal/vagal nucleus, which have been shown to have very slow desensitization kinetics. 3. The results indicate that the AMPA receptors of the cochlear ganglion, nucleus magnocellularis and nucleus laminaris share a number of structural and functional properties that distinguish them from the AMPA receptors of brainstem motor neurons, namely a lower relative abundance of glutamate receptor (GluR)2 transcript and much lower levels of GluR2 immunoreactivity, higher relative levels of GluR3 flop and GluR4 flop, lower relative abundance of the C-terminal splice variants GluR4c and 4d, less R/G editing of GluR2 and 3, greater permeability to calcium, predominantly inwardly rectifying I-V relationships, and greater susceptibility to block by Joro spider toxin. 4. We conclude that the AMPA receptors of auditory neurons acquire rapid kinetics from their high content of GluR3 flop and GluR4 flop subunits and their high permeability to Ca2+ from selective post-transcriptional suppression of GluR2 expression.

Animals↗
PubMed1996

Development of the time coding pathways in the auditory brainstem of the barn owl.

The barn owl's head grows after hatching, causing interaural distances to more than double in the first 3 weeks posthatch. These changes expose the bird to a constantly increasing range of interaural time cues. We have used Golgi and ultrastructural techniques to analyze the development of the connections and cell types of the nucleus magnocellularis (NM) and the nucleus laminaris (NL) with reference to the growth of the head. The time coding circuit is formed but immature at the time of hatching. In the month posthatch, the auditory nerve projection to the NM matures, and appears adult-like by posthatch day (P)21. NM neurons show a late growth of permanent dendrites starting at P6. Over the first month, these dendrites change in length and number, depending upon rostrocaudal position, to establish the adult pattern in which high best frequency neurons have few or no dendrites. These changes are not complete by P21, when NM neurons still have more dendrites than in the adult owl. The neurons of NL have many short dendrites before hatching. Their number is greatly reduced by P6, and then does not change during later development. Like NM neurons, NL neurons and dendrites grow in the first month posthatch, and at P21, NL dendrites are longer than those in the adult owl. Thus, the auditory brainstem circuits grow in the first month after hatching, but are not yet mature at the time the head reaches its adult size.

Animals↗
PubMed2002

Inferior colliculus unitary activity in wakefulness, sleep and under barbiturates.

The spontaneous unitary activity and the response to contralateral tone-burst were analyzed in the inferior colliculus (IC) of guinea pigs during the sleep-waking cycle and under the effects of pentobarbital anesthesia. Minor changes were observed in both spontaneous and evoked activity between wakefulness (W) and slow wave sleep (SWS). On the other hand, a consistent increase in the mean spontaneous firing rate and a significant decrement in the signal-to-noise ratio (S/N ratio) was observed during paradoxical sleep (PS). Pentobarbital anesthesia reduced the spontaneous and evoked firing rate, the duration of the excitatory response and increased the duration of the post-excitatory suppression. We conclude, that the processing of auditory information in the IC change markedly during PS. Because the IC is a compulsory station for almost all the ascending auditory pathways, the observed decrease in the S/N ratio may deeply affect the auditory perception during this behavioral state. Finally, the alteration of the neuronal activity induced by pentobarbital differs not only with the activity observed during W, but also with the activity observed during both SWS and PS.

Acoustic Stimulation↗
PubMed2006

Basis of electrical stimulation of the cochlea and the cochlear nucleus.

Sensorineural hearing loss is the most common form of deafness in humans. In patients with a severe-profound sensorineural hearing loss therapeutic intervention can only be achieved by direct electrical stimulation of the auditory nerve via a cochlear implant, or - in cases where a cochlear implant is not a surgical option - neurons within the central auditory pathway via an auditory brainstem implant. This paper reviews the basis of electrical stimulation of these structures with an emphasis on pathophysiology and safety.

Animals↗
PubMed1995

Limited protective effects of etomidate during brainstem ischemia in dogs.

To evaluate etomidate as a neuroprotective agent in the brain stem, 33 dogs were divided into seven groups and were exposed to isolated, reversible brainstem ischemia in the presence or absence of etomidate using a newly developed canine model of brainstem ischemia. Brainstem auditory evoked potentials (BAEP) and regional cerebral blood flow were measured during ischemia and for 5 hours after reperfusion. This model provides a potential physiological environment in which to test the efficacy of putative brainstem ischemic protective strategies. During ischemia, BAEP were abolished in all animals. Without etomidate 10 minutes of ischemia was of short enough duration to allow complete recovery of BAEP. Ischemia of 20 or 30 minutes' duration resulted in minimal recovery. The dose of etomidate administered did not suppress BAEP or brainstem cardiovascular response to ischemia. In animals receiving etomidate and rendered ischemic for 20 minutes, a significant but only temporary recovery in BAEP was seen. Etomidate failed to have a significant effect in animals rendered ischemic for 30 minutes. The minimal effect of etomidate on the current measures of brainstem function is in contrast to etomidate's known suppressive effect on cortical electroencephalogram and predicts that etomidate does little to alter brainstem metabolism. Etomidate's failure to provide for permanent recovery of BAEP suggests that the drug does not give sufficient protection from ischemia to the brainstem neurons in the auditory pathway. If these auditory neurons reflect brainstem function as a whole, etomidate may not be the protective agent of choice during temporary arterial occlusion of posterior circulation.

Animals↗
PubMed2000

Memory consolidation of auditory pavlovian fear conditioning requires protein synthesis and protein kinase A in the amygdala.

Previous studies have shown that long-term potentiation (LTP) can be induced in the lateral nucleus of the amygdala (LA) after stimulation of central auditory pathways and that auditory fear conditioning modifies neural activity in the LA in a manner similar to LTP. The present experiments examined whether intra-LA administration of inhibitors of protein synthesis or protein kinase A (PKA) activity, treatments that block LTP in hippocampus, interfere with memory consolidation of fear conditioning. In the first series of experiments, rats received a single conditioning trial followed immediately by intra-LA infusions of anisomycin (a protein synthesis inhibitor) or Rp-cAMPS (an inhibitor of PKA activity) and were tested 24 hr later. Results indicated that immediate post-training infusion of either drug dose-dependently impaired fear memory retention, whereas infusions 6 hr after conditioning had no effect. Additional experiments showed that anisomycin and Rp-cAMPS interfered with long-term memory (LTM), but not short-term memory (STM), of fear and that the effect on LTM was specific to memory consolidation processes rather than to deficits in sensory or performance processes. Findings suggest that the LA is essential for memory consolidation of auditory fear conditioning and that this process is PKA and protein-synthesis dependent.

Acoustic Stimulation↗
PubMed1981

Tinnitus: development of a neurophysiologic correlate.

Although tinnitus severely afflicts 7.2 million Americans, the pathophysiology of this problem remains obscure because there presently exists no good animal model in which to study the phenomenon. We have examined changes in activity in the guinea pig auditory pathway using an autoradiographic method of functional brain mapping after short-term and long-term cochlear ablations which can, in humans, initiate the occurrence of tinnitus. With this method we have observed a reduction in activity in various nuclei in the auditory pathway between 4 hrs and 10 days after unilateral cochlear ablation. In contrast to these findings we have found a return of activity in these same nuclei if they are observed from 12 to 48 days following the lesion. These preliminary data suggest that this return of activity in the absence of sensory input may be a valid experimental analogue for tinnitus in humans. Such evidence for auditory plasticity may represent a significant first step toward understanding this common and profound otologic symptom.

Animals↗