Papers of the Week

Tinnitus affects roughly 15-20% of the population while severely impacting 10% of those afflicted. Tinnitus pathology is multifactorial, generally initiated by damage to the auditory periphery, resulting in a cascade of maladaptive plastic changes at multiple levels of the central auditory neuraxis as well as limbic and non-auditory cortical centers. Using a well-established condition-suppression model of tinnitus, we measured tinnitus-related changes in the microcircuits of excitatory/inhibitory neurons onto layer 5 pyramidal neurons (PNs), as well as changes in the excitability of vasoactive intestinal peptide (VIP) neurons in primary auditory cortex (A1). Patch-clamp recordings from PNs in A1 slices showed tinnitus-related increases in spontaneous excitatory postsynaptic currents (sEPSCs) and decreases in spontaneous inhibitory postsynaptic currents (sIPSCs). Both measures could be correlated to the rat’s behavioral evidence of tinnitus. Tinnitus-related changes in PN excitability were independent of changes in A1 excitatory or inhibitory cell numbers. VIP neurons, part of an A1 local circuit that can control the excitation of layer 5 PNs via disinhibitory mechanisms, showed significant tinnitus-related increases in excitability that directly correlated with the rat’s behavioral tinnitus score. That PN and VIP changes directly correlated to tinnitus behavior, suggests an important role in A1 tinnitus pathology. Tinnitus-related A1 changes were similar to findings in studies of neuropathic pain in somatosensory cortex suggesting a common pathology of these troublesome perceptual impairments. Improved understanding between excitatory, inhibitory and disinhibitory sensory cortical circuits can serve as a model for testing therapeutic approaches to the treatment of tinnitus and chronic pain. KEY POINTS: Identify tinnitus-related changes in synaptic function of specific neuronal subtypes in a reliable animal model of tinnitus. Finding show direct and indirect tinnitus-related losses of normal inhibitory function at A1 layer 5 pyramidal cells, and increased VIP excitability. Findings are similar to what has been shown for neuropathic pain suggesting that restoring normal inhibitory function at synaptic inputs onto A1 pyramidal neurons could conceptually reduce tinnitus discomfort. Abstract figure legend A, B. Noise-exposed animals with behavioral evidence of tinnitus show poor ability to distinguish tone from silence. C. Whole cell patch-clamp recordings from layer 5 pyramidal neurons and (D) VIP+ GABAergic neurons showed significant tinnitus-related increases in excitatory responses. Pyramidal neurons also showed a significant loss of inhibitory input (disinhibition). E. Collectively, tinnitus-related changes were directly correlated to the animal’s tinnitus score. This article is protected by copyright. All rights reserved.