November 24, 2020

Pharmacological inhibition of an epigenetic regulator during the formation of extinction memory reveals sensory cortical and subcortical codes for the specificity of salient cues.

Using a sound-reward extinction paradigm in male rats, we reveal both cortical and subcortical sensory codes for the cue-specificity of memory. In the auditory cortex, re-tuning narrowed frequency receptive field bandwidth, yielding more precise extinction behavior cued by acoustic frequency. Subcortical signals revealed in the auditory brainstem response (ABR) showed decreases in amplitude of select components of the ABR wave. Interestingly, treatment with an inhibitor of histone deacetylase 3 (HDAC3-i) facilitated both auditory cortical tuning bandwidth changes and ABR changes that were frequency-specific to the extinguished signal sound. Moreover, both changes were correlated to each other and with highly precise extinction memory at the level of behavior. Thus, we show for the first time that HDAC3 regulates the specificity of sensory features consolidated in extinction memory. Overall, the dynamics of auditory system plasticity associated with sound-specific extinction are complex. Changes in ABR amplitude induced by sound-reward learning disappeared after extinction, while changes in ABR slope that were initially induced by sound-reward learning were maintained through extinction. Moreover, plasticity of cortical re-tuning emerged only after extinction learning. HDAC3-i applied after extinction training sessions enabled sensory system plasticity to encode the extinguished sound with higher acoustic specificity (compared to vehicle controls). Both cortical and subcortical response changes to sound became unusually "tuned-in" to the acoustic frequency that had been presented under extinction conditions. Thus, HDAC3 regulates how specifically sensory features of experience are encoded into long-term memory and may exert its behavioral effects via multiple coding strategies along sensory system pathways.

 bioRxiv Subject Collection: Neuroscience

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