Learning induces unique transcriptional landscapes in the auditory cortex

Learning can induce neurophysiological plasticity in the auditory cortex at multiple timescales. Lasting changes to auditory cortical function that persist over days, weeks, or even a lifetime, require learning to induce de novo gene expression. Indeed, transcription is the molecular determinant for long-term memories to form with a lasting impact on sound-related behavior. However, auditory cortical genes that support auditory learning, memory, and acquired sound-specific behavior are largely unknown. Using an animal model of adult, male Sprague-Dawley rats, this report is the first to identify genome-wide changes in learning-induced gene expression within the auditory cortex that may underlie long-lasting discriminative memory formation of acoustic frequency cues. Auditory cortical samples were collected from animals in the initial learning phase of a two-tone discrimination sound-reward task known to induce sound-specific neurophysiological and behavioral effects. Bioinformatic analyses on gene enrichment profiles from bulk RNA sequencing identified cholinergic synapse (KEGG rno04725), extra-cellular matrix receptor interaction (KEGG rno04512), and neuroactive receptor interaction (KEGG rno04080) among the top biological pathways are likely to be important for auditory discrimination learning. The findings characterize candidate effectors underlying the early stages of changes in cortical and behavioral function to ultimately support the formation of long-term discriminative auditory memory in the adult brain. The molecules and mechanisms identified are potential therapeutic targets to facilitate experiences that induce long-lasting changes to sound-specific auditory function in adulthood and prime for future gene-targeted investigations.