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. This report is the first to identify in young adult male rats (Sprague-Dawley) genome-wide changes in learning-induced gene expression within the auditory cortex that may underlie the formation of long-lasting discriminative memory for 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 (e.g., Shang et al., 2019). Bioinformatic analyses on gene enrichment profiles from bulk RNA sequencing identified cholinergic synapse (KEGG 04725), extra-cellular matrix receptor interaction (KEGG 04512), and neuroactive ligand-receptor interaction (KEGG 04080) as top biological pathways for auditory discrimination learning. The findings characterize key candidate effectors underlying changes in cortical function that support the initial formation of long-term discriminative auditory memory in the adult brain. The molecules and mechanisms identified are potential therapeutic targets to facilitate lasting changes to sound-specific auditory function in adulthood and prime for future gene-targeted investigations.