Bimodal stimulus timing-dependent plasticity in primary auditory cortex is altered after noise exposure with and without tinnitus

Abstract

Basura GJ, Koehler SD, Shore SE. Bimodal stimulus timingdependent plasticity in primary auditory cortex is altered after noise exposure with and without tinnitus. J Neurophysiol 114: 3064 -3075, 2015. First published August 19, 2015 doi:10.1152/jn.00319.2015.-Central auditory circuits are influenced by the somatosensory system, a relationship that may underlie tinnitus generation. In the guinea pig dorsal cochlear nucleus (DCN), pairing spinal trigeminal nucleus (Sp5) stimulation with tones at specific intervals and orders facilitated or suppressed subsequent tone-evoked neural responses, reflecting spike timing-dependent plasticity (STDP). Furthermore, after noiseinduced tinnitus, bimodal responses in DCN were shifted from Hebbian to anti-Hebbian timing rules with less discrete temporal windows, suggesting a role for bimodal plasticity in tinnitus. Here, we aimed to determine if multisensory STDP principles like those in DCN also exist in primary auditory cortex (A1), and whether they change following noise-induced tinnitus. Tone-evoked and spontaneous neural responses were recorded before and 15 min after bimodal stimulation in which the intervals and orders of auditory-somatosensory stimuli were randomized. Tone-evoked and spontaneous firing rates were influenced by the interval and order of the bimodal stimuli, and in sham-controls Hebbian-like timing rules predominated as was seen in DCN. In noise-exposed animals with and without tinnitus, timing rules shifted away from those found in sham-controls to more anti-Hebbian rules. Only those animals with evidence of tinnitus showed increased spontaneous firing rates, a purported neurophysiological correlate of tinnitus in A1. Together, these findings suggest that bimodal plasticity is also evident in A1 following noise damage and may have implications for tinnitus generation and therapeutic intervention across the central auditory circuit.

Efficacy of stimulus intensity increases and decreases as inhibitors of the acoustic startle response

“…These findings cohere with animal studies of Basura et al (), Ralli et al (), Shore et al (), and Turner et al (), which showed that a gap (stimulus intensity decrease) may be useful in studying lab‐induced tinnitus; it was proposed that the internally generated sound perceived by the animals would fill a silent gap and diminish or remove inhibition that would have been caused by the gap, resulting in larger magnitude startle responses, compared to those of control animals. The results from the current study can explain the findings to a further degree: If tinnitus constitutes an inability to hear silence, and hence fills a gap, less inhibition would be expected on decrease trials than on increase trials, but partial inhibition of startle magnitude would still be expected.…”

“…Animals can be conditioned to respond to the termination of noise, and the inability to detect the cessation of noise after salicylate exposure is a model of tinnitus (Jastreboff & Sasaki, 1994;Ruttiger, Ciuffani, Zenner, & Knipper, 2003). Across a variety of studies, the induced tinnitus-like animals have been shown to demonstrate less inhibition of startle magnitude on fully silent gap trials, compared to control animals (Basura, Koehler, & Shore, 2015;Ralli et al, 2014;Shore, Roberts, & Langguth, 2016;Turner, Larson, Hughes, Moechars, & Shore, 2012). These findings suggest that the tinnitus-associated sound perception partially fills the silent gap, reducing the expected inhibition of startle responding.…”

Maladaptive plasticity in tinnitus — triggers, mechanisms and treatment

“…Burst firing increased immediately after noise trauma but subsided to normal over the measurement period of a few hours while the changes in SFR and synchrony persisted. While tinnitus was not measured in these experiments, subsequent studies confirmed that there was increased cortical synchrony and SFR in animals with verified tinnitus, using the GPIAS, giving credence to the validity of hyperactivity and synchrony as neural correlates of tinnitus [72]. …”

Can Animal Models Contribute to Understanding Tinnitus Heterogeneity in Humans?

“…If one believes that increased SFR in the auditory nervous system, and particularly in ACx, is a neural correlate of tinnitus (Eggermont and Roberts, 2004; Roberts et al, 2010; Basura et al, 2015), then a few additional noise-exposure effects demand attention. After a single TTS-causing exposure—which constitutes the bulk of current animal experiments involving gap-startle indications of tinnitus—one often finds increased SFRs and the gap-startle reflex indicates (Salloum et al, 2014, 2016) the presence of tinnitus.…”

“…An overview of some of these findings, augmented with results from Basura et al (2015) and Wu et al (2016) that are likely TTS causing, is presented in Table 4 . Again, assuming that increased SFRs in ACx suggest the presence of tinnitus, one has to come to the conclusion that tinnitus cannot only occur in humans with clinical normal thresholds (≤25 dB HL) but also with absolute normal thresholds (Gu et al, 2010; Melcher et al, 2013).…”