Sound processing in the mouse auditory cortex: organization, modulation, and transformation

The auditory system begins with the cochlea, a frequency analyzer and signal amplifier with exquisite precision. As neural information travels towards higher brain regions, the encoding becomes less faithful to the sound waveform itself and more influenced by non-sensory factors such as top-down attentional modulation, local feedback modulation, and long-term changes caused by experience. At the level of auditory cortex (ACtx), such influences exhibit at multiple scales from single neurons to cortical columns to topographic maps, and are known to be linked with critical processes such as auditory perception, learning, and memory. How the ACtx integrates a wealth of diverse inputs while supporting adaptive and reliable sound representations is an important unsolved question in auditory neuroscience. This dissertation tackles this question using the mouse as an animal model. We begin by describing a detailed functional map of receptive fields within the mouse ACtx. Focusing on the frequency tuning properties, we demonstrated a robust tonotopic organization in the core ACtx fields (A1 and AAF) across cortical layers, neural signal types, and anesthetic states, confirming the columnar organization of basic sound processing in ACtx. We then studied the bottom-up input to ACtx columns by optogenetically activating the inferior colliculus (IC), and observed feedforward neuronal activity in the frequency-matched column, which also induced clear auditory percepts in behaving mice. Next, we used optogenetics to study layer 6 corticothalamic neurons (L6CT) that project heavily to the thalamus and upper layers of ACtx. We found that L6CT activation biases sound perception towards either enhanced detection or discrimination depending on its relative timing with respect to the sound, a process that may support dynamic filtering of auditory information. Finally, we optogenetically isolated cholinergic neurons in the basal forebrain (BF) that project to ACtx and studied their involvement in columnar ACtx plasticity during associative learning. In contrast to previous notions that BF just encodes reward and punishment, we observed clear auditory responses from the cholinergic neurons, which exhibited rapid learning-induced plasticity, suggesting that BF may provide a key instructive signal to drive adaptive plasticity in ACtx