The dorsal cochlear nucleus (DCN) is the first neural site of bimodal auditory-somatosensory integration. Previous studies have shown that stimulation of somatosensory pathways results in immediate suppression or enhancement of subsequent acoustically-evoked discharges. In the unimpaired auditory system suppression predominates. However, damage to the auditory input pathway leads to enhancement of excitatory somatosensory inputs to the cochlear nucleus, changing their effects on DCN neurons (Zeng et al., 2009; Shore et al., 2008). Given the well described connection between the somatosensory system and tinnitus in patients we sought to determine if plastic changes in long lasting bimodal somatosensory-auditory processing accompany tinnitus. Here we demonstrate for the first time in vivo long-term effects of somatosensory inputs on acoustically-evoked discharges of DCN neurons in guinea pigs. The effects of trigeminal nucleus stimulation are compared between normal-hearing animals and animals overexposed with narrow band noise and behaviorally tested for tinnitus. The noise exposure resulted in a temporary threshold shift (TTS) in auditory brainstem responses but a persistent increase in spontaneous and sound-evoked DCN unit firing rates and increased steepness of rate-level functions (RLFs). Rate increases were especially prominent in buildup units. The long-term somatosensory enhancement of sound-evoked responses was strengthened while suppressive effects diminished in noise-exposed animals, especially those that developed tinnitus. Damage to the auditory nerve (ANF) is postulated to trigger compensatory long-term synaptic plasticity of somatosensory inputs that might be an important underlying mechanism for tinnitus generation.

Spherical bushy cells (SBCs) of the anteroventral cochlear nucleus (AVCN) receive their main excitatory input from auditory nerve fibers (ANFs) through large synapses, endbulbs of Held. These cells are also the target of inhibitory inputs whose function is not well understood. The present study examines the role of inhibition in the encoding of low-frequency sounds in the gerbil's AVCN. The presynaptic action potentials of endbulb terminals and postsynaptic action potentials of SBCs were monitored simultaneously in extracellular single-unit recordings in vivo. An input-output analysis of presynaptic and postsynaptic activity was performed for both spontaneous and acoustically driven activity. Two-tone stimulation and neuropharmacological experiments allowed the effects of neuronal inhibition and cochlear suppression on SBC activity to be distinguished.Ninety-one percent of SBCs showed significant neuronal inhibition. Inhibitory sidebands enclosed the high-or lowfrequency, or both, sides of the excitatory areas of these units; this was reflected as a presynaptic to postsynaptic increase in frequency selectivity of up to one octave. Inhibition also affected the level-dependent responses at the characteristic frequency. Although in all units the presynaptic recordings showed monotonic rate-level functions, this was the case in only half of the postsynaptic recordings. In the other half of SBCs, postsynaptic inhibitory areas overlapped the excitatory areas, resulting in nonmonotonic rate-level functions. The results demonstrate that the sound-evoked spike activity of SBCs reflects the integration of acoustically driven excitatory and inhibitory input. The inhibition specifically affects the processing of the spectral, temporal, and intensity cues of acoustic signals. Key words: prepotential units; endbulb of Held; cochlear suppression; neuronal inhibition; in vivo physiology; bicuculline; strychnine; gerbil; spherical bushy cells; cochlear nucleusThe cochlear nucleus consists of three subdivisions: the anteroventral cochlear nucleus (AVCN), the posteroventral cochlear nucleus, and the dorsal cochlear nucleus, each of which establishes the origins of several monaural and binaural ascending pathways (for review, see Irvine, 1986). It was believed previously that the AVCN serves primarily as a relay transmitting a highfidelity copy of the activity of the auditory nerve to more central auditory brainstem nuclei (Pfeiffer, 1966a,b;Rose et al., 1974). This was demonstrated by morphological data which show that the principal neurons of the AVCN, the spherical bushy cells (SBCs), are innervated by only two to four auditory nerve fibers (ANFs) that form large synaptic endbulbs on the somata of the neurons (Brawer and Morest, 1975;Ryugo and Sento, 1991;Bazwinsky et al., 1999). Because of this specific synaptic configuration, electrophysiological recordings using extracellular electrodes can detect the postsynaptic action potentials of SBCs together with a preceding "prepotential" (PP), indicating the presynaptic afferent ANF ...

Tinnitus or ringing of the ears is a subjective phantom sensation necessitating behavioral models that objectively demonstrate the existence and quality of the tinnitus sensation. The gap detection test uses the acoustic startle response elicited by loud noise pulses and its gating or suppression by preceding sub-startling prepulses. Gaps in noise bands serve as prepulses, assuming that ongoing tinnitus masks the gap and results in impaired gap detection. This test has shown its reliability in rats, mice, and gerbils. No data exists for the guinea pig so far, although gap detection is similar across mammals and the acoustic startle response is a well-established tool in guinea pig studies of psychiatric disorders and in pharmacological studies. Here we investigated the startle behavior and prepulse inhibition (PPI) of the guinea pig and showed that guinea pigs have a reliable startle response that can be suppressed by 15 ms gaps embedded in narrow noise bands preceding the startle noise pulse. After recovery of auditory brainstem response (ABR) thresholds from a unilateral noise over-exposure centered at 7 kHz, guinea pigs showed diminished gap-induced reduction of the startle response in frequency bands between 8 and 18 kHz. This suggests the development of tinnitus in frequency regions that showed a temporary threshold shift (TTS) after noise over-exposure. Changes in discharge rate and synchrony, two neuronal correlates of tinnitus, should be reflected in altered ABR waveforms, which would be useful to objectively detect tinnitus and its localization to auditory brainstem structures. Therefore, we analyzed latencies and amplitudes of the first five ABR waves at suprathreshold sound intensities and correlated ABR abnormalities with the results of the behavioral tinnitus testing. Early ABR wave amplitudes up to N3 were increased for animals with tinnitus possibly stemming from hyperactivity and hypersynchrony underlying the tinnitus percept. Animals that did not develop tinnitus after noise exposure showed the opposite effect, a decrease in wave amplitudes for the later waves P4–P5. Changes in latencies were only observed in tinnitus animals, which showed increased latencies. Thus, tinnitus-induced changes in the discharge activity of the auditory nerve and central auditory nuclei are represented in the ABR.

Purpose This review outlines the anatomical and functional bases of somatosensory influences on auditory processing in the normal brainstem and midbrain. Thereafter, it explores how interactions between the auditory and somatosensory system are modified through deafness and their impact on tinnitus is discussed. Methods literature-review, tract-tracing, immunohistochemistry, in vivo electrophysiological recordings Results Somatosensory input originates in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) and is transmitted directly and indirectly through second order nuclei to the ventral and dorsal cochlear nucleus (VCN, DCN) and inferior colliculus (IC). The glutamatergic somatosensory afferents can be segregated from auditory nerve inputs by the type of vesicular glutamate transporters present in their terminals. Electrical stimulation of the somatosensory input results in a complex combination of excitation and inhibition and alters the rate and timing of responses to acoustic stimulation. Deafness increases the spontaneous rates of those neurons that receive excitatory somatosensory input, and results in a greater sensitivity of DCN neurons to trigeminal stimulation. Conclusions Auditory-somatosensory bimodal integration is already present in first order auditory nuclei. The balance of excitation and inhibition elicited by somatosensory input is altered following deafness. The increase in somatosensory influence on auditory neurons when their auditory input is diminished could be due to cross modal re-innervation or increased synaptic strength, and may contribute to mechanisms underlying somatic tinnitus.

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