Biology subjects

Rotondo, E. K.

Publications and source records attributed to Rotondo, E. K..

3 recordsLinked to original sources

bioRxiv2021

Memory specific to temporal features of sound is formed by cue-selective enhancements in temporal coding enabled by inhibition of an epigenetic regulator

Recent investigation of memory-related functions in the auditory system have capitalized on the use of memory-modulating molecules to probe the relationship between memory and its substrates in auditory system coding. For example, epigenetic mechanisms, which regulate gene expression necessary for memory consolidation, are powerful modulators of learning-induced neuroplasticity and long-term memory formation (LTM). Inhibition of the epigenetic regulator histone deacetylase 3 (HDAC3) promotes LTM that is highly specific for spectral features of sound. The present work demonstrates for the first time that HDAC3 inhibition also enables memory for temporal features of sound. Rats trained in an amplitude modulation (AM) rate discrimination task and treated with a selective inhibitor of HDAC3 formed memory that was unusually specific to the AM rate paired with reward. Unusually sound-specific memory revealed behaviorally was associated with a signal-specific enhancement in temporal coding in the auditory system: stronger phase-locking that was specific to the rewarded AM rate was revealed in both the surface-recorded frequency following response (FFR) and auditory cortical multiunit activity in rats treated with the HDAC3-inhibitor. Furthermore, HDAC3inhibition increased trial-to-trial cortical response consistency (relative to naive and trained vehicle-treated rats) that generalized across different AM rates. Stronger signal-specific phase-locking correlated with individual behavioral differences in memory specificity for the AM signal. Together, these findings support that epigenetic mechanisms regulate activity-dependent processes that enhance discriminability of sensory cues encoded into LTM in both spectral and temporal domains, which may be important for remembering spectrotemporal features of sounds, e.g., as in human voices and speech. SIGNIFICANCE STATEMENTEpigenetic mechanisms have recently been implicated in memory and information processing. Here, we use a pharmacological inhibitor of histone deacetylase 3 (HDAC3) in a sensory model of learning to reveal, for the first time, its ability to enable unusually precise memory for amplitude modulated sound cues. In so doing, we uncover neural substrates for memorys "specificity" for temporal sound cues. Memory specificity was supported by auditory cortical changes in temporal coding, including greater response consistency and stronger phase-locking. HDAC3 appears to regulate effects across domains that determine specific cue saliency for behavior. Thus, epigenetic players may gate how sensory information is stored in long-term memory and can be leveraged to reveal the neural substrates of sensory details stored in memory.

animal behavior and cognition↗

bioRxiv2020

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. SIGNIFICANCE STATEMENTEpigenetic mechanisms have recently been implicated in memory and information processing. Here, we use a pharmacological inhibitor of histone deacetylase 3 (HDAC3) in a sensory model of learning to reveal, for the first time, its ability to enable unusually precise extinction memory. In so doing, we uncover neural coding strategies for memorys "specificity" for sensory cues. Extinction induced multiple forms of change at different levels of sensory processing, which highlights the complexity of extinction memory encoding. HDAC3 appears to coordinate effects across sensory levels that determine specific cue saliency for behavior. Thus, epigenetic players may gate how sensory information is stored in long-term memory and their manipulation can be leveraged to reveal neural coding mechanisms for sensory detail in memory.

neuroscience↗

bioRxiv2019

Precise memory is predicted by learning-induced sensory system neurophysiological plasticity

Despite identical learning experiences, individuals differ in the memory formed of those experiences. Memory formed with sensory specificity determines its utility for selectively cueing subsequent behavior, even in novel situations. If an individual forms generalized memory, then there is potential for novel sensory cues to interfere with accurate behavioral performance. Here, a rodent model of auditory learning capitalized on individual differences in learning-induced auditory neuroplasticity to identify and characterize neural substrates for sound-specific (vs. general) memory of the training signals acoustic frequency. Animals with naturally or pharmacologically induced signal-\"specific\" memory revealed behaviorally, exhibited long-lasting signal-specific neurophysiological plasticity in auditory cortical and subcortical evoked responses, while learning-induced changes were not detected in animals with \"general\" memories. Individual differences validated this brain-behavior relationship, such that the degree of change in neurophysiological responses could be used to determine the precision of memory formation.

neuroscience↗