Sensation

Projects on this research theme focus on how neural activity in the auditory processing centers of the brain give rise to the perception of sound. In human subjects, we tackle this question by studying electric field fluctuations on the surface of the head. In animal models, we leverage recent advances in two-photon calcium imaging, multi-channel electrophysiology and optogenetic methods to measure and manipulate genetically defined cell types in behaving mice. Our work in mice and humans is primarily focused on how normal auditory processing goes off the rails following hearing loss to create debilitating perceptual disorders.

Paradoxically, two of the most common and debilitating sequelae of adult hearing loss arise not from what is inaudible, but rather from the irrepressible perception of sounds that do not exist (tinnitus) or the perception that moderately intense sounds are intolerably loud or painful (hyperacusis). Tinnitus and hyperacusis are most often triggered by damage to cochlear hair cells or nerve endings in the inner ear. However, inner ear pathology is neither necessary nor sufficient to cause the perception of tinnitus or hyperacusis. Much like phantom limb pain in the somatosensory system, tinnitus and hyperacusis directly arise from a brain plasticity process that has run amok. When afferent signaling from the peripheral nervous system declines due to damage or aging, the balance of excitation and inhibition tips toward hyperexcitability throughout the central auditory system. Our work has shown that hypersensitizing central auditory neurons increases the “gain” on diminished peripheral inputs and restores activity levels and perceptual thresholds to homeostatic set points. When turned up too high, central gain disrupts normal spike patterning in auditory centers of the brain, distorting neural representations of complex communication sounds, such as speech in noise, and induces the constant, disruptive and often aversive perception of faint or non-existent sounds.

Techniques used

  • Chronic 2-photon and widefield calcium imaging from genetically defined cortical cell types
  • Optogenetic approaches to activate, silence or "tag" genetically defined cell types
  • Extracellular single unit recordings from the inferior colliculus, medial geniculate body and auditory cortex of awake mice with multi-channel probes.
  • Estimates of auditory perceptual thresholds via mouse operant behavioral testing
  • Traditional markers of auditory function (auditory brainstem response, otoacoustic emission measurements, and startle reflex audiometry)
  • EEG, pupillometry and psychoacoustic measures of detection and discrimination thresholds

Lead researchers

Supported by

R01 DC009836, P50 DC015817, Lauer Tinnitus Research Center