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Neural mechanisms underlying somatic tinnitus - PubMed

Review

Neural mechanisms underlying somatic tinnitus

Susan Shore et al. Prog Brain Res. 2007.

Abstract

Somatic tinnitus is clinically observed modulation of the pitch and loudness of tinnitus by somatic stimulation. This phenomenon and the association of tinnitus with somatic neural disorders indicate that neural connections between the somatosensory and auditory systems may play a role in tinnitus. Anatomical and physiological evidence supports these observations. The trigeminal and dorsal root ganglia relay afferent somatosensory information from the periphery to secondary sensory neurons in the brainstem, specifically, the spinal trigeminal nucleus and dorsal column nuclei, respectively. Each of these structures has been shown to send excitatory projections to the cochlear nucleus. Mossy fibers from the spinal trigeminal and dorsal column nuclei terminate in the granule cell domain while en passant boutons from the ganglia terminate in the granule cell domain and core region of the cochlear nucleus. Sources of these somatosensory-auditory projections are associated with proprioceptive and cutaneous, but not nociceptive, sensation. Single unit and evoked potential recordings in the dorsal cochlear nucleus indicate that these pathways are physiologically active. Stimulation of the dorsal column and the cervical dorsal root ganglia elicits short- and long-latency inhibition separated by a transient excitatory peak in DCN single units. Similarly, activation of the trigeminal ganglion elicits excitation in some DCN units and inhibition in others. Bimodal integration in the DCN is demonstrated by comparing responses to somatosensory and auditory stimulation alone with responses to paired somatosensory and auditory stimulation. The modulation of firing rate and synchrony in DCN neurons by somatatosensory input is physiological correlate of somatic tinnitus.

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Figures

Fig. 1
Fig. 1

Projections from Sp5 to the CN in the guinea pig. (A–G) Retrograde labeling in the brainstem after an injection of biotinylated dextran amine (BDA) into the CN. (A) Photomicrograph of the injection site. The injection site is virtually restricted to the shell region of the PVCN. (B–D): Drawings of 1 mm transverse sections across the medulla. Each dot represents one labeled cell. The labeled neurons are located primarily on the ipsilateral side of Sp5, in the Sp5I and Sp5C. Very few labeled cells, if any, are located in the SG (D). Labeled neurons can also be found in the medular reticular formation (RVL and LPGi, C), inferior olive (IO, C), and dorsal column nuclei (Gr and Cu, D). Projection neurons in Sp5 have either polygonal or elongated somata (E). Projection neurons in dorsal column nuclei and reticular formation are multipolar (F and G). (H) Terminal labeling in the CN after placement of an anterograde tracer into Sp5I. Most Sp5 fibers enter the CN via DAS/IAS and terminate primarily in the GCD (gray area), but also in deep DCN. Each dot represents one to three labeled terminal endings. Scale bars = 25 μm (E–G). (Abbreviations: CN, cochlear nucleus; Cu, cuneate nucleus; DAS, dorsal acoustic striae; DCN, dorsal cochlear nucleus; GCD, granule cell domain; Gr, gracile nucleus; IAS, intermediate acoustic striae; IO, inferior olive; LPGi, lateral paragigantocellular reticular nucleus; PVCN, posteroventral cochlear nucleus; RVL, rostral ventrolateral reticular formation; SG, subnucleus gelatinosus; Sp5, spinal trigeminal nucleus; Sp5C, pars caudalis of Sp5; Sp5I, pars interpolaris of Sp5; Sp5O, pars oralis of Sp5).

Fig. 2
Fig. 2

High magnification confocal images (63×) showing colocalization of anterogradely labeled Sp5 terminal endings with VGLUT2-ir in the CN. Green, VGLUT-ir. Red, Sp5 labeling. Yellow, double labeled terminals. Figures were obtained from Z projections of stacks of serial 1 μm confocal images. (A) MFs are labeled with BDA from Sp5 and VGLUT2 in the shell region of the VCN (arrow). (B) Small boutons are labeled with BDA from Sp5 and VGLUT2 in the DCN layer 2 (arrows). (C and D) Sp5 terminal endings do not colabel with VGLUT1 in the shell region of the VCN and the core of the VCN. Scale bar = 10 μm in D (applies to A–C). (See Color Plate 10.2 in color plate section.)

Fig. 3
Fig. 3

High magnification 1 μm confocal images (63×) showing colocalization of AN terminal endings with VGLUT1-ir, but not VGLUT2-ir, in both the VCN and deep layer of the DCN. Green, VGLUT-ir. Red, FG filled AN fibers and endings. Yellow, double-labeled terminals. (A and B) Colocalization of AN terminal endings with VGLUT1-ir in VCN (A) and DCN layer 3 (B). Both endbulb-like AN endings (arrows in A) and small boutons (arrowheads in A and B) colabeled with the VGLUT1. (C and D) VGLUT2 did not label the AN endings in both VCN (C) and DCN layer 3 (D). Scale bar = 20 μm in D (applies to A–C). (See Color Plate 10.3 in color plate section.)

Fig. 4
Fig. 4

Poststimulus time histograms of DCN unit responses to trigeminal ganglion stimulation show inhibition. Responses of four unit clusters from 4 channels (9, 10, 12, 13) of 16-channel electrode are shown. Stimulation was at 80 μA, 100 ms/phase bipolar pulses, 100 presentations. Bin width, 0.5 ms. Arrow — electrical stimulus artifact indicates onset of TG stimulation. Inset at right shows location of the stimulating electrode in the ophthalmic region of the TG.

Fig. 5
Fig. 5

Poststimulus time histograms of DCN unit responses to trigeminal ganglion stimulation show excitation. Responses of four different unit clusters from 4 channels (4, 10, 11, 12) of a 16-channel electrode in the same animal but different penetration as for Fig. 4, are shown. Stimulation was at 80 μA, 100 ms/phase bipolar pulses, 100 presentations. Bin width, 0.5 ms. Arrow — electrical stimulus artifact indicates onset of TG stimulation. Inset at right shows location of the stimulating electrode in the ophthalmic region of the TG.

Fig. 6
Fig. 6

Configuration of the mulitchannel electrode used to record responses shown in Figs. 3 and 4. The four shank, 16-channel electrodes are positioned on the dorsal aspect of the DCN and lowered into the fusiform cell layer (layer 2) of the DCN. Often responses from multiunit clusters are recorded from each channel, which are then sorted using the Plexon offline sorter, into single units.

Fig. 7
Fig. 7

(A) Poststimulus time histograms of a DCN single unit’s response to TG stimulation combined with acoustic stimulation. The TG pulse precedes the acoustic stimulus (broadband noise at 30 dB SPL) by varying amounts designated by dt. Acoustic stimulus duration is indicated by red bar below histograms. Arrow indicates onset of TG pulse (80 μA, 100 ms/phase bipolar pulses, 100 presentations). Responses to three different dt values are shown. Preceding the acoustic stimulus by TG stimulation results in a diminished response to the acoustic stimulus. The effect is stronger when the two stimuli are closer. Bin width, 0.5 ms. Arrow —electrical stimulus artifact indicates onset of TG stimulation. (B) Quantification of the spike rates achieved in (a) for unit 16. Spike rates for two other units, 5a and 5b, are also shown. Insets: Poststimulus time histograms for responses to BF tonebursts indicate unit types; Unit 16 is a P-Buildup; Unit 5b may be a cartwheel cell.

Fig. 8
Fig. 8

Poststimulus time histograms of a different DCN single unit’s response to TG stimulation combined with acoustic stimulation. The TG pulse precedes the acoustic stimulus (broadband noise at 30 dB SL) by 5 ms. Acoustic stimulus duration is 200 ms, indicated by red bar below histograms. Arrow indicates onset of TG pulse (80 μA, 100 ms/phase bipolar pulses, 100 presentations). In this unit, preceding the acoustic stimulus by TG stimulation results in an enhanced response to the acoustic stimulus. Note, the buildup pattern of response indicates that this cell was likely a pyramidal cell.

Fig. 9
Fig. 9

Schematic of DCN circuitry. Pyramidal cells (Py) in layer II of the DCN receive inputs on their basal dendrites from auditory nerve fibers (a.n.f.) and vertical (v) cells. The apical dendrites of the pyramidal cells receive inputs from the parallel fiber axons (pf) from granule cells (gr) in the VCN, while their cell bodies receive inputs from cartwheel (Ca) and superficial stellate (st) cells. Projections from the trigeminal ganglion (TG), spinal trigeminal nucleus (Sp5), dorsal column nuclei (Gracile and cuneate n), and the dorsal root ganglion (DRG), synapse on granule cells. (See Color Plate 10.9 in color plate section.)

Fig. 10
Fig. 10

Rate-level functions for two different units in ICx (A and B) in response to broadband noise stimuli (100 ms, 5 ms risefall times) with and without Sp5 stimulation. Trigeminal stimulus was at the onset of the acoustic stimulus. Response to Sp5 stimulation alone was minimal, but Sp5 stimulation reduced the responses of units in A and B to sound stimulation. The effects were more pronounced at low sound levels. (Adapted with permission from Jain and Shore, 2006.) (See Color Plate 10.10 in color plate section.)

Plate 10.2
Plate 10.2

High magnification confocal images (63 ×) showing colocalization of anterogradely labeled Sp5 terminal endings with VGLUT2-ir in the CN. Green, VGLUT-ir. Red, Sp5 labeling. Yellow, double labeled terminals. Figures were obtained from Z projections of stacks of serial 1 μm confocal images. (A) MFs are labeled with BDA from Sp5 and VGLUT2 in the shell region of the VCN (arrow). (B) Small boutons are labeled with BDA from Sp5 and VGLUT2 in the DCN layer 2 (arrows). (C and D) Sp5 terminal endings do not colabel with VGLUT1 in the shell region of the VCN and the core of the VCN. Scale bar = 10 μm in D (applies to A–C). (For B/W version, see page 112 in the volume.)

Plate 10.3
Plate 10.3

High magnification 1 μm confocal images (63 ×) showing colocalization of AN terminal endings with VGLUT1-ir, but not VGLUT2-ir, in both the VCN and deep layer of the DCN. Green, VGLUT-ir. Red, FG filled AN fibers and endings. Yellow, double-labeled terminals. (A and B) Colocalization of AN terminal endings with VGLUT1-ir in VCN (A) and DCN layer 3 (B). Both endbulb-like AN endings (arrows in A) and small boutons (arrowheads in A and B) colabeled with the VGLUT1. (C and D) VGLUT2 did not label the AN endings in both VCN (C) and DCN layer 3 (D). Scale bar = 20 μm in D (applies to A–C). (For B/W version, see page 113 in the volume.)

Plate 10.9
Plate 10.9

Schematic of DCN circuitry. Pyramidal cells (Py) in layer II of the DCN receive inputs on their basal dendrites from auditory nerve fibers (a.n.f.) and vertical (v) cells. The apical dendrites of the pyramidal cells receive inputs from the parallel fiber axons (pf) from granule cells (gr) in the VCN, while their cell bodies receive inputs from cartwheel (Ca) and superficial stellate (st) cells. Projections from the trigeminal ganglion (TG), spinal trigeminal nucleus (Sp5), dorsal column nuclei (Gracile and cuneate n), and the dorsal root ganglion (DRG), synapse on granule cells. (For B/W version, see page 119 in the volume.)

Plate 10.10
Plate 10.10

Rate-level functions for two different units in ICx (A and B) in response to broadband noise stimuli (100 ms, 5 ms risefall times) with and without Sp5 stimulation. Trigeminal stimulus was at the onset of the acoustic stimulus. Response to Sp5 stimulation alone was minimal, but Sp5 stimulation reduced the responses of units in A and B to sound stimulation. The effects were more pronounced at low sound levels. (Adapted with permission from Jain and Shore, 2006.) (For B/W version, see page 120 in the volume.)

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