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.

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.

Remodeling sensory cortical maps implants specific behavioral memory.

Neural mechanisms underlying the capacity of memory to be rich in sensory detail are largely unknown. A candidate mechanism is learning-induced plasticity that remodels the adult sensory cortex. Here, expansion in the primary auditory cortical (A1) tonotopic map of rats was induced by pairing a 3.66-kHz tone with activation of the nucleus basalis, mimicking the effects of natural associative learning. Remodeling of A1 produced de novo specific behavioral memory, but neither memory nor plasticity was consistently at the frequency of the paired tone, which typically decreased in A1 representation. Rather, there was a specific match between individual subjects' area of expansion and the tone that was strongest in each animal's memory, as determined by post-training frequency generalization gradients. These findings provide the first demonstration of a match between the artificial induction of specific neural representational plasticity and artificial induction of behavioral memory. As such, together with prior and present findings for detection, correlation and mimicry of plasticity with the acquisition of memory, they satisfy a key criterion for neural substrates of memory. This demonstrates that directly remodeling sensory cortical maps is sufficient for the specificity of memory formation.