Abstract
Layer 5 (L5) cortical projection neurons innervate far-ranging brain areas to coordinate integrative sensory processing and adaptive behaviors. Here, we characterize a compensatory plasticity in L5 auditory cortex (ACtx) projection neurons with axons that innervate the inferior colliculus (IC), thalamus, lateral amygdala and striatum. We used widefield calcium imaging to monitor daily changes in sound processing from the dense plexus of corticocollicular (CCol) axon terminals in awake adult mice. CCol sound level growth functions were stable in control conditions but showed bi-phasic gain changes following damage to cochlear afferent synapses. Auditory nerve and CCol growth functions were sharply reduced hours after cochlear synaptopathy, but CCol response gain rebounded above baseline levels by the following day and remained elevated for 2 weeks despite a persistent reduction in auditory nerve input. Sustained potentiation of excitatory ACtx projection neurons that innervate multiple limbic and subcortical auditory centers may underlie hyperexcitability and aberrant functional coupling of distributed brain networks in tinnitus.
