Synaptic properties of layer 6 auditory corticothalamic inputs in normal hearing and noise-induced hearing loss.

Layer 6 corticothalamic neurons (CTs) provide strong feedback input that is crucial to perception and cognition in normal and pathological states; however, the synaptic properties of this input remain largely unknown, especially in pathology. Here, we examined the synaptic properties of CT axon terminals in the medial geniculate body (MGB), the auditory thalamus, in normal hearing male and female mice and in a mouse model of noise-induced hearing loss, also in male and female mice. In normal hearing mice, we found that the amplitude of CT-evoked excitatory postsynaptic current (EPSC) to the core-type ventral subdivision of the auditory thalamus (MGv), which mainly conveys rapid sensory information, is larger compared to the amplitude of CT-evoked EPSC to the matrix-type dorsal subdivision of the auditory thalamus (MGd), which likely conveys higher-order internal state information. This is due to higher axonal density and/or axonal recruitment in CT→MGv compared to CT→MGd synapses. After noise trauma, we observed enhanced short-term facilitation in CT→MGd but not CT→MGv synapses. Our findings reveal a previously unknown mechanism of short-term synaptic plasticity after noise-induced hearing loss via which CTs enhance the throughput of matrix-type thalamus, likely to improve perceptual recovery via higher-order contextual modulation.Significance Statement Auditory layer 6 corticothalamic neurons (CTs) send massive projections to the auditory thalamus, the medial geniculate body (MGB). This pathway is crucial for sound perception and cognition. However, the synaptic properties of this pathway under either normal or pathological hearing remain poorly understood. We found enhanced evoked synaptic responses between CT and the ventral (CT→MGv) compared to CT and the dorsal (CT→MGd) MGB subdivision. Importantly, we discovered an enhancement of activity-dependent facilitation at the CT→MGd synapses after noise-induced hearing loss, thus highlighting a plasticity mechanism that might enhance perceptual recovery via higher-order cortico-thalamo-cortical modulation.