Evidence of activity-dependent plasticity in the dorsal cochlear nucleus, in vivo, induced by brief sound exposure.

The purpose of the present study was to investigate the immediate effects of acute exposure to intense sound on spontaneous and stimulus-driven activity in the dorsal cochlear nucleus (DCN). We examined the levels of multi- and single-unit spontaneous activity before and immediately following brief exposure (2 min) to tones at levels of either 109 or 85 dB SPL. Exposure frequency was selected to either correspond to the units' best frequency (BF) or fall within the borders of its inhibitory side band. The results demonstrate that these exposure conditions caused significant alterations in spontaneous activity and responses to BF tones. The induced changes have a fast onset (minutes) and are persistent for durations of at least 20 min. The directions of the change were found to depend on the frequency of exposure relative to BF. Transient decreases followed by more sustained increases in spontaneous activity were induced when the exposure frequency was at or near the units' BF, while sustained decreases of activity resulted when the exposure frequency fell inside the inhibitory side band. Follow-up studies at the single unit level revealed that the observed activity changes were found on unit types having properties which have previously been found to represent fusiform cells. The changes in spontaneous activity occurred despite only minor changes in response thresholds. Noteworthy changes also occurred in the strength of responses to BF tones, although these changes tended to be in the direction opposite those of the spontaneous rate changes. We discuss the possible role of activity-dependent plasticity as a mechanism underlying the rapid emergence of increased spontaneous activity after tone exposure and suggest that these changes may represent a neural correlate of acute noise-induced tinnitus.

Gao Y ，Manzoor N ，Kaltenbach JA 《-》

Hyperactivity in the dorsal cochlear nucleus after intense sound exposure and its resemblance to tone-evoked activity: a physiological model for tinnitus.

Kaltenbach JA ，Afman CE 《HEARING RESEARCH》

Muscarinic acetylcholine receptors control baseline activity and Hebbian stimulus timing-dependent plasticity in fusiform cells of the dorsal cochlear nucleus.

Cholinergic modulation contributes to adaptive sensory processing by controlling spontaneous and stimulus-evoked neural activity and long-term synaptic plasticity. In the dorsal cochlear nucleus (DCN), in vitro activation of muscarinic acetylcholine receptors (mAChRs) alters the spontaneous activity of DCN neurons and interacts with N-methyl-d-aspartate (NMDA) and endocannabinoid receptors to modulate the plasticity of parallel fiber synapses onto fusiform cells by converting Hebbian long-term potentiation to anti-Hebbian long-term depression. Because noise exposure and tinnitus are known to increase spontaneous activity in fusiform cells as well as alter stimulus timing-dependent plasticity (StTDP), it is important to understand the contribution of mAChRs to in vivo spontaneous activity and plasticity in fusiform cells. In the present study, we blocked mAChRs actions by infusing atropine, a mAChR antagonist, into the DCN fusiform cell layer in normal hearing guinea pigs. Atropine delivery leads to decreased spontaneous firing rates and increased synchronization of fusiform cell spiking activity. Consistent with StTDP alterations observed in tinnitus animals, atropine infusion induced a dominant pattern of inversion of StTDP mean population learning rule from a Hebbian to an anti-Hebbian profile. Units preserving their initial Hebbian learning rules shifted toward more excitatory changes in StTDP, whereas units with initial suppressive learning rules transitioned toward a Hebbian profile. Together, these results implicate muscarinic cholinergic modulation as a factor in controlling in vivo fusiform cell baseline activity and plasticity, suggesting a central role in the maladaptive plasticity associated with tinnitus pathology.NEW & NOTEWORTHY This study is the first to use a novel method of atropine infusion directly into the fusiform cell layer of the dorsal cochlear nucleus coupled with simultaneous recordings of neural activity to clarify the contribution of muscarinic acetylcholine receptors (mAChRs) to in vivo fusiform cell baseline activity and auditory-somatosensory plasticity. We have determined that blocking the mAChRs increases the synchronization of spiking activity across the fusiform cell population and induces a dominant pattern of inversion in their stimulus timing-dependent plasticity. These modifications are consistent with similar changes established in previous tinnitus studies, suggesting that mAChRs might have a critical contribution in mediating the maladaptive alterations associated with tinnitus pathology. Blocking mAChRs also resulted in decreased fusiform cell spontaneous firing rates, which is in contrast with their tinnitus hyperactivity, suggesting that changes in the interactions between the cholinergic and GABAergic systems might also be an underlying factor in tinnitus pathology.

Stefanescu RA ，Shore SE 《-》

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

Kaltenbach JA ，Zhang J 《HEARING RESEARCH》

Alterations in the spontaneous discharge patterns of single units in the dorsal cochlear nucleus following intense sound exposure.

Electrophysiological recordings in the dorsal cochlear nucleus (DCN) were conducted to determine the nature of changes in single unit activity following intense sound exposure and how they relate to changes in multiunit activity. Single and multiunit spontaneous discharge rates and auditory response properties were recorded from the left DCN of tone exposed and control hamsters. The exposure condition consisted of a 10 kHz tone presented in the free-field at a level of 115 dB for 4h. Recordings conducted at 5-6 days post-exposure revealed several important changes. Increases in multiunit spontaneous neural activity were observed at surface and subsurface levels of the DCN of exposed animals, reaching a peak at intermediate depths corresponding to the fusiform cell layer and upper level of the deep layer. Extracellular spikes from single units in the DCN of both control and exposed animals characteristically displayed either M- or W-shaped waveforms, although the proportion of units with M-shaped spikes was higher in exposed animals than in controls. W-shaped spikes showed significant increases in the duration of their major peaks after exposure, suggestive of changes in the intrinsic membrane properties of neurons. Spike amplitudes were not found to be significantly increased in exposed animals. Spontaneous discharge rates of single units increased significantly from 8.7 spikes/s in controls to 15.9 spikes/s after exposure. Units with the highest activity in exposed animals displayed type III electrophysiological responses patterns, properties usually attributed to fusiform cells. Increases in spontaneous discharge rate were significantly larger when the comparison was limited to a subset of units having type III frequency response patterns. There was an increase in the incidence of simple spiking activity as well as in the incidence of spontaneous bursting activity, although the incidence of spikes occurring in bursts was low in both animal groups (i.e., <30%). Despite this low incidence, approximately half of the increase in spontaneous activity in exposed animals was accounted for by an increase in bursting activity. Finally, we found no evidence of an increase in the mean number of spontaneously active units in electrode penetrations of exposed animals compared to those in controls. Overall our results indicate that the increase in multiunit activity observed at the DCN surface reflects primarily an increase in the spontaneous discharge rates of single units below the DCN surface, of which approximately half was contributed by spikes in bursts. The highest level of hyperactivity was observed among units having the response properties most commonly attributed to fusiform cells.

Finlayson PG ，Kaltenbach JA 《-》