Jinsheng Zhang

Activity in the dorsal cochlear nucleus of hamsters previously tested for tinnitus following intense tone exposure

Chronic increases in spontaneous multiunit activity can be induced in the dorsal cochlear nucleus (DCN) of hamsters by intense sound exposure (Kaltenbach and McCaslin, 1996). It has been hypothesized that this hyperactivity may represent a neural code that could underlie the sound percepts of tinnitus. The goal of the present study was to determine whether hyperactivity could be demonstrated in animals that had previously been tested for tinnitus, and, if so, whether animals differing in their behavioral evidence for tinnitus also differ in their levels of spontaneous activity. The results showed not only that levels of activity in exposed animals were higher than those in control animals, but the degree to which the activity was increased was related to the strength of the behavioral evidence for tinnitus. These findings are consistent with the hypothesis that hyperactivity in the DCN may be a physiological correlate of noise-induced tinnitus.

Tinnitus as a plastic phenomenon and its possible neural underpinnings in the dorsal cochlear nucleus.

Tinnitus displays many features suggestive of plastic changes in the nervous system. These can be categorized based on the types of manipulations that induce them. We have categorized the various forms of plasticity that characterize tinnitus and searched for their neural underpinnings in the dorsal cochlear nucleus (DCN). This structure has been implicated as a possible site for the generation of tinnitus-producing signals owing to its tendency to become hyperactive following exposure to tinnitus inducing agents such as intense sound and cisplatin. In this paper, we review the many forms of plasticity that have been uncovered in anatomical, physiological and neurochemical studies of the DCN. Some of these plastic changes have been observed as consequences of peripheral injury or as fluctuations in the behavior and chemical activities of DCN neurons, while others can be induced by stimulation of auditory or even non-auditory structures. We show that many parallels can be drawn between the various forms of plasticity displayed by tinnitus and the various forms of neural plasticity which have been defined in the DCN. These parallels lend further support to the hypothesis that the DCN is an important site for the generation and modulation of tinnitus-producing signals.

Plasticity of spontaneous neural activity in the dorsal cochlear nucleus after intense sound exposure

Increases in multiunit spontaneous activity (hyperactivity) can be induced in the dorsal cochlear nucleus (DCN) by intense sound exposure. This hyperactivity has been observed in the hamster and rat following exposure to a 10 kHz tone at a level of 125-130 dB SPL for a period of 4 h. The present study demonstrates that the onset of this hyperactivity is not immediate, but develops in the DCN between 2 and 5 days after exposure. Mean rates of multiunit spontaneous activity increased sharply from below normal levels at day 2 to higher than normal levels at day 5. The mean magnitude of activity continued to increase more gradually over the next 6 months. During this period, changes in the distribution of hyperactivity across the tonotopic array were also noted. The hyperactivity was more broadly distributed across the DCN at the early post-exposure times (5 and 14 days) than at later post-exposure recovery times (30 and 180 days), and peak activity was found at increasingly more medial positions over this time frame. These changes over time indicate that the mechanisms leading to hyperactivity following intense sound exposure are more complex than previously realized.

Increases in spontaneous activity in the dorsal cochlear nucleus of the rat following exposure to high-intensity sound

The effects of intense sound exposure on neural activity in the dorsal cochlear nucleus (DCN) were studied in the rat. Seventeen anesthetized adult rats were exposed to a 10-kHz tone at 125-130 dB SPL for 4 h. Fourteen unexposed rats served as controls. Spontaneous activity (SA) and neural thresholds at the characteristic frequency were measured in three rows of 8-12 sites along the mediolateral, tonotopic, axis of the DCN surface 27-61 days after exposure. The results showed that intense tone exposure induced chronic increases in SA. This hyperactivity was found to be distributed broadly across the DCN with an emphasis around the 10-kHz locus and was associated with shifted response thresholds. These findings demonstrate the usefulness of the rat for studies of physiological phenomena related to noise-induced tinnitus and hearing loss.

Changes in spontaneous neural activity in the dorsal cochlear nucleus following exposure to intense sound : Relation to threshold shift

Previous studies have shown that the dorsal cochlear nucleus exhibits increased spontaneous activity after exposure to intense sound. Such increases were apparent 1-2 months after the exposure and were generally proportional to the shift in response thresholds induced by the same exposure. The purpose of the present study was to determine whether this sound-induced increase in spontaneous activity is an early event which can be observed shortly after exposure. As in previous studies, anesthetized hamsters ranging in postnatal age from 60-70 days were exposed to a 10-kHz tone at levels between 125 and 130 dB SPL for a period of 4 h. Control animals were similarly anesthetized but were not exposed to the intense tone. Exposed animals were examined in two groups, one at 30 days after exposure, the other at 2 days after exposure. Time of exposure was adjusted so that all animals were between 90 and 100 days of age when spontaneous activity was studied electrophysiologically. The results showed that the increases in spontaneous activity, which were evident at 30 days after exposure, were not observed in animals studied 2 days after exposure. This result contrasted with the effect of the intense tone exposure on neural response thresholds. That is, the shifts in response thresholds seen 2 days after exposure were similar to those observed in animals studied 30 days after exposure. These results indicate that changes in spontaneous activity reflect a more slowly developing phenomenon and occur secondarily after induction of threshold shift.

Effects of cochlear ablation on noise induced hyperactivity in the hamster dorsal cochlear nucleus: Implications for the origin of noise induced tinnitus

Chronic increases in multiunit spontaneous activity are induced in the dorsal cochlear nucleus (DCN) following exposures to intense sound. This hyperactivity has been implicated as a neurophysiological correlate of noise induced tinnitus. However, it is not known whether this hyperactivity originates centrally, or instead, reflects an increase in the level of spontaneous input from the auditory nerve. In the present study we addressed this issue by testing whether hyperactivity, induced in the DCN by previous exposure to intense sound, persists after ipsilateral cochlear input to the DCN has been removed. To induce hyperactivity, Syrian golden hamsters were exposed under anesthesia to an intense pure tone (122-127 dB SPL at 10 kHz) for 4 h. Additional hamsters, which were anesthetized for 4 h, but not tone exposed, served as controls. Electrophysiological recordings of spontaneous activity were performed on the surface of the left DCN in animals in which the ipsilateral cochlea was either intact or ablated. The degree of cochlear removal was determined by microdissection and histologic evaluation of the cochlea after completion of each recording session. Comparisons between the levels of activity recorded in animals with and without intact cochleas revealed that the induced hyperactivity in the DCN persisted after both partial and complete cochlear ablations. These results indicate that the maintenance of hyperactivity is not dependent on input from the ipsilateral cochlea, implying that hyperactivity originates centrally.

Effects of acoustic trauma on dorsal cochlear nucleus neuron activity in slices

Previous studies found increased multi-unit spontaneous activity in the dorsal cochlear nucleus (DCN) of animals that had been exposed to intense sound. Such activity may be related to tinnitus. Our study examined effects of previous exposure to intense sound on single neurons in the DCN, by measuring spontaneous activities and sensitivities to acetylcholine, an important neurotransmitter of centrifugal pathways to the cochlear nucleus, in brain slices. Spontaneous discharges were recorded extracellularly in the DCN portion of brain slices from control and intense-tone-exposed rats. Slices from exposed rats showed increased prevalence of bursting and decreased regular spontaneous activity. Since regular neurons include fusiform cells, and bursting neurons include cartwheel cells, intense tone exposure may lead to increased activity of DCN cartwheel cells and decreased activity of fusiform cells. Alternatively, the activity of some fusiform cells might change to bursting. Intense tone exposure also appeared to increase bursting neuron sensitivity to carbachol. This suggests that changes in DCN cartwheel cell spontaneous activity may reflect changes in effects of cholinergic centrifugal pathways following intense tone exposure. We conclude that acoustic trauma may lead to changes in the physiology and pharmacology of DCN neurons. These changes may be related to underlying mechanisms of central tinnitus.

Electrically induced Fos-like immunoreactivity in the auditory pathway of the rat: Effects of survival time, duration, and intensity of stimulation

The goal of the present study was to establish how Fos-like immunoreactivity (FLI) elicited in the rat auditory pathway by unilateral electric stimulation of the cochlea is affected by the following experimental parameters: duration and intensity of stimulation, duration of survival time after offset of stimulation. The dense FLI found in the ipsilateral dorsal cochlear nucleus, as well as the moderate FLI found in the contralateral dorsal cochlear nucleus and in the posteroventral cochlear nucleus on both sides, were consistent after survival times ranging from 0 to 2-3 h, but they significantly decreased after longer survival times (5 and 6 h). In the same nuclei, FLI was increased even by short durations of stimulation (5 and 10 min) as compared to control rats, although FLI progressively increased for longer stimulation (20 and 45 min). In the auditory thalamus, FLI was found mainly in the peripeduncular nucleus, the dorsal and medial divisions of the medial geniculate body, whereas its ventral division was virtually devoid of immunoreactive neurons. This pattern of FLI distribution in the auditory thalamus persisted even after relatively long survival times (5 and 6 h). In both the cochlear nucleus and auditory thalamus, the density of FLI slightly increased in parallel with the intensity of stimulation. In other auditory nuclei, such as the inferior colliculus and the nucleus of the lateral lemniscus, there was no simple relation between the density of FLI and the three tested experimental parameters. Thus, the distribution and density of FLI did not vary in parallel in the various nuclei of the auditory pathway as a function of the tested experimental parameters; different patterns of FLI changes were instead observed in different auditory nuclei.

Direct electrical stimulation of Heschl's gyrus for tinnitus treatment.

Objectives/Hypothesis: The purpose of the study was to determine the effect of electrical stimulation of the auditory cortex in patients with tinnitus.

Intense sound-induced plasticity in the dorsal cochlear nucleus of rats : Evidence for cholinergic receptor upregulation

Previous studies in a number of species have demonstrated that spontaneous activity in the dorsal cochlear nucleus (DCN) becomes elevated following exposure to intense sound. This condition of hyperactivity has aroused considerable interest because it may represent an important neural correlate of tinnitus. There is some evidence that neurons in the superficial DCN, such as cartwheel, stellate and fusiform cells, may contribute to the level of hyperactivity induced by intense sound, although the relative importance of these different cell types is unknown. In the present study, we sought to determine the effect of intense sound exposure on multiunit spontaneous activity both at the DCN surface and in the fusiform cell layer and to examine the influence of cholinergic input to DCN circuits on the level of activity in the fusiform cell layer. Rats were studied in two groups, one of which had been exposed to a continuous intense sound (10 kHz 127 dB SPL) for 4h while the other group served as unexposed controls. Between 30 and 52 days post-exposure, recordings of multiunit activity were performed at the DCN surface as well as in the middle of the fusiform cell layer. Changes in fusiform cell layer activity were also studied in response to superficial applications of the cholinergic agonist, carbachol, either alone or following pre-application of the cholinergic antagonist, atropine. The results demonstrated that multiunit spontaneous activity in the rat DCN was generally much higher in both control and exposed animals relative to that which has been observed in other species. This activity was significantly higher at the DCN surface of sound-exposed animals than that of controls. In contrast, hyperactivity could not be demonstrated in the fusiform cell layer of sound-exposed animals. Carbachol administration most commonly caused suppression of fusiform cell layer activity. However, this suppression was considerably stronger in the DCN of sound-exposed animals than in controls. These findings suggest that, hyperactivity at the DCN surface of exposed rats may arise as a consequence of more highly activated neurons in the molecular layer, such as cartwheel and/or stellate cells, and that the lack of hyperactivity in the fusiform cell layer may be the result of inhibition of fusiform cells by these inhibitory interneurons. Although this finding does not rule out fusiform cells as possible sources of hyperactivity in other species, or even in the rat after short post-exposure recovery periods, the enhanced sensitivity of the fusiform cell layer to cholinergic stimulation suggests that in the rat, at least after prolonged post-exposure recovery periods, increased inhibition of activity in this layer by more superficially located neurons may result from an upregulation of receptors for cholinergic input. This upregulation may be greater in rats than in other species due to the relatively heavy cholinergic input that exists in the cochlear nucleus of this species.