Plasticity of somatosensory inputs to the cochlear nucleus--implications for tinnitus

Abstract

This chapter reviews evidence for functional connections of the somatosensory and auditory systems at the very lowest levels of the nervous system. Neural inputs from the dosal root and trigeminal ganglia, as well as their brain stem nuclei, cuneate, gracillis and trigeminal, terminate in the cochlear nuclei. Terminations are primarily in the shell regions surrounding the cochlear nuclei but some terminals are found in the magnocellular regions of cochlear nucleus. The effects of stimulating these inputs on multisensory integration are shown as short and long-term, both suppressive and enhancing. Evidence that these projections are glutamatergic and are altered after cochlear damage is provided in the light of probable influences on the modulation and generation of tinnitus.

Copyright © 2011 Elsevier B.V. All rights reserved.

Figures

Figure 1

Terminals from thin axons of the trigeminal ganglion end in the small cell cap (SCC) region of the anteroventral cochlear nucleus (AVCN). A transverse section (inset) of the ventral cochlear nucleus (VCN) is drawn, indicating the location of terminals by stippling. Large arrow points to an expanded drawing of some of these terminals at upper left. Small arrow points to photomicrograph at lower right, showing an expanded view of some of the terminals. The axons typically form boutons de passage. D, dorsal; M, medial. Large scale bar = 5 μm; small scale bar = 10 μm. From Shore et al., 2000.

Figure 2

Reconstruction of anterograde terminal labeling in guinea pig CN.A: BDA injection site in pars interpolaris of Sp5 (Sp5I). B–G: Drawings of transverse sections from the rostral to caudal ends of CN. Each dot represents one or more terminal endings. Thin lines represent labeled fibers. Marginal area and granular cell layers of CN are outlined by redlines. Boxed area in E represents the area of photomicrograph displayed in Figure 3. CN, cochlear nucleus; Cu, cuneate nucleus; AVCN, anteroventral CN; PVCN, posteroventral CN; DCN, dorsal CN; DAS, dorsal acoustic striae; Gr, gracile nucleus; IAS, intermediate acoustic striae; icp, inferior cerebellar peduncle; Sp5, Spinal trigeminal nucleus; sp5, spinal trigeminal tract; Sp5I, pars interpolaris of Sp5; tz, trapezoid body; 7n, facial nerve; 8vn, vestibular nerve. H. Photomicrographs of labeled rat mossy fibers that are distinguished from terminal boutons by their larger size and lobulated appearance. Filiform appendages that terminate in small swellings are also evident. Mossy fibers from the spinal trigeminal nucleus are found restricted to the GCD. Scale bar = 10 μm. A–G from Zhou and Shore, 2000. H. From Haenggelli et al., 2005.

Figure 3

High-magnification confocal images (×63) showing colocalization of anterogradely labeled Sp5 terminal endings with VGLUT2-ir in the CN small cell cap (SCC). Green, VGLUT-ir; red, Sp5 labeling; yellow, double-labeled terminals. A–D were obtained from Z projections of stacks of serial 1-μm confocal images and each show a single, 1-μm confocal image. Insets in AB show a single 1-μm confocal image. A–B: MFs are labeled with VGLUT2 (A) and BDA from Sp5. Colocalization of Sp5 MFs with VGLUT2-ir is indicated by arrowhead in B. C–D: High-magnification confocal images showing colocalization of anterogradely labeled VIII th nerve terminal endings with VGLUT1-ir in AVCNm. VIII th nerve terminals are labeled with BDA injected into the cochlea. Colocalization of VIII th nerve terminals with VGLUT1-ir is indicated by arrows in in C. Note no co-localization of VIII th nerve terminals with VGLUT2 (D). Scale bar = 10 μm. Green, VGLUT, yellow, double-labeled terminals. E–F: Percentages of Sp5 and ANF terminals labeled with VGLUTs. Stars represent significant differences (p < .1; bars represent standard errors of the mean). From Zhou et al., 2007.

Figure 4

Long-term changes in the tone-evoked firing rate after dorsal column(DCoN) stimulation. Examples from 3 neurons in which the effects of a DCoN stimulus pulse lasted for the duration of the 200 ms acoustic stimulus. A:DCoN stimulation at 2 delta-t values increased the tone-evoked firing rate of a tonic neuron by 41.9 and 108.1%, respectively (top traces); compare the black control PSTHs with the red with-shock PSTHs. Small or no differences occurred in the spontaneous rates (“spont”). To quantify the significance of rate changes, the rate differences (with-shock minus no-shock) are plotted below (bottom green traces, smoothed with 5-bin triangular filter) together with horizontal lines showing ±1 SD of the spontaneous rate from the PSTHs. Significant rate changes are present where the rate differences are outside the ±1 SD area. Note that large rate differences persist for the duration of the stimulus. B: Apauser neuron in which DCoN stimulation also increased the tone-evoked firing rate by 125 and 146.5%, respectively. Also note the increase in the onset peak at dt = 20 ms. C: pauser response in which the long-term effect was a decrease in discharge rate. For this case, the shock and no-shock trials were interleaved on alternating trials, as opposed to A and B where they were interleaved with other stimuli in 100-repetition sets. PSTHs (except rate differences) were not smoothed. D-E: Bimodal enhancement in a single unit from the DCN of aguinea pig: Responses of a single unit to broadband noise (BBN) alone, and preceded by trigeminal ganglion stimulation are shown in D and E, respectively. The response to combined trigeminal and acoustic stimulation is larger than the response to sound stimulation alone, indicating enhancing bimodal integration. F–G: Bimodal suppression: Responses of a single unit to broadband noise (BBN) alone, and preceded by trigeminal ganglion stimulation are shown in F and G, respectively. The response to combined trigeminal and acoustic stimulation in this case is smaller than the response to sound stimulation alone, indicating suppressive bimodal integration that lasted throughout the duration of the sound-evoked response. Responses of both units to BF tones were buildup. BBN level, 50 dB SPL (30 dB SL); current, 80 μA. Trigeminal stimulus precedes BBN by 5 ms. Solid bar above graphs shows the onset and duration of the BBN; arrow indicates onset of the bipolar trigeminal pulse (100 μs/phase). Bin width, 1 ms. An example of the magnitude of this effect is shown as percent integration in E. Insets to panels G and H represent the unit waveforms for these two units. From Shore, 2005. From: Kanold et al., 2011 (A–C); Shore 2005 (D–F).

Figure 5

Spinal trigeminal nucleus (Sp5) stimulation changes firing rate and regularity in dorsal cochlear nucleus (DCN) presumed pyramidal cells. Firing rate is suppressed and regularity of the acoustic response is decreased when sound is preceded by Sp5 stimulation. (A, A1 and A2) Identical responses of a chopper unit response to BF tones are shown prior to bimodal stimulation. (A3) Bimodal response showing suppressive integration. (A4 and A5) Partially recovered acoustic responses at 5 and 10 min following the collection of bimodal responses. (B) Raster plot and PSTH of a chopper unit response to BF tones (top, same as A2) and BF tones preceded by Sp5 stimulation (bottom, same as A3). (C) Raster plot and PSTH of a pauser unit response to BF tones (top) and BF tones preceded by Sp5 stimulation (bottom). (D) Raster plot and PSTH of a chopper unit response to BF tones (top) and BF tones preceded by Sp5 stimulation (bottom). Each PSTH is composed of 200 trials. In each raster plot, each point represents a spike and each row represents a single stimulus trial. The bottom row is the first trial. Solid gray bars indicate the duration of the acoustic stimulus. Gray bars with black borders indicate the duration of electrical stimulation of Sp5. The average value of the transient CV (tCV) is indicated above each response in (B), (C) and (D). From Koehler et al., 2011.

Figure 6

VGLUT1-ir is decreased, whereas VGLUT2 is increased in the CN ipsilateral to the cochlear damage. Photomicrographs of VGLUT1-ir from the VCNm of one animal contralateral (A) and ipsilateral (B) to the cochlear damage, 2 weeks after kanamycin injections into the left cochlea. VGLUT1 is strongly expressed in PVCNm on the control side (B) as previously shown (Zhou et al., 2007) but weakly expressed ipsilateral to the deafening (A). The decrease in VGLUT1-ir reflects primarily decreased VIIIth nerve synaptic inputs after kanamycin injections into the cochlea. C,D, Photomicrographs of VGLUT2-ir from SHELL regions of CN. VGLUT2-ir in the ipsilateral SHELL region is increased ipsilateral (C) to the cochlear damage compared with the contralateral side (D). Scale bars: A–B, 50 μm; C,D20 μm. E. shows ratio plots (after deafening/before deafening) for VGLUT1 and VGLUT2 across CN regions. From Zeng et al., 2009.

Figure 7

(A) Mean spontaneous rates (SRs) for dorsal cochlear nucleus single units at 1 and 2 weeks after noise exposure at 120 dB SPL. SR is significantly higher at 1 week following exposure (Bonferroni-adjusted comparison; *P < 0.05). (B) Frequency distribution plots indicate that the increased SR is accounted for mostly by an increase in the number of medium SR values. (C) The distribution of SRs by responses to trigeminal stimulation indicates that only units that are activated by trigeminal stimulation (those that display excitatory and excitatory/inhibitory responses) showed increased SRs after noise exposure. Units that were inhibited by trigeminal stimulation and units that did not respond to trigeminal stimulation did not show increased SR after noise damage. Error bars are standard errors of the mean. From Shore et al., (2008).