Functional representation of behavioral memory specificity in auditory cortex
Creators: name: Shang, Andrea
Publisher: name: No Publisher Supplied
Year: 2021

description: An open question in neuroscience is the role of sensory systems in cognitive processes like memory. That sensory representations in the adult brain can be modified by experience posits a functional role for sensory systems in adaptive behavior (McGann, 2015). This dissertation focuses on the auditory system, specifically the auditory cortex, which has long been implicated in functions for learning and remembering sound (Weinberger, 2007). The overarching hypothesis is that learning-related changes to the properties of sound-evoked auditory cortical responses can encode for particular attributes of associative memory, which range from its temporal dynamics, e.g., long-lastingness over time and persistence, to its content, e.g., specificity and fidelity to the experienced sounds. Here, we focus on the putative role of auditory cortex to represent auditory memory’s specificity. Because memory specificity appears to be influenced by a molecular regulator called histone deacetylase 3 (Bieszczad et al., 2015), we leveraged pharmacological inhibition of HDAC3 (HDAC3i) to promote the specificity of auditory memory formed from associative frequency discrimination training, and to probe corresponding forms of auditory cortical neuroplasticity. In Chapter 1, we find increased acuity and precision of associative memory for both signal tone frequencies in animals treated with the HDAC3-inhibitor (relative to vehicle-treated controls), validating a role for HDAC3 in regulating the sensory details encoded into memory. We also report here for the first time that limited HDAC3-inhibitor treatment early in associative learning (post-training injections after the first 3 days of discrimination training) is sufficient to induce long-lasting effects on associative auditory memory and cortical representation of learned sounds. Auditory cortical recordings conducted at the end of behavioral training, up to 2 weeks from the last HDAC3 inhibitor treatment, identified signal-specific narrowing of tuning bandwidths form as a likely neural substrate of frequency discrimination learning. It is important to note that the tuning changes in HDAC3i-treated animals were persistent even up to 4 weeks after the final training session, at a time point when vehicle-treated animals also began to show signal-specific tuning changes. This suggests that HDAC3i expedited a natural physiological process for encoding highly specific sound information to memory. Next, we asked whether a behavioral consequence of reducing cortical tuning bandwidth was to decrease the overlap in cortical representation for the learned tone-frequencies. If so, a finer acoustic frequency discrimination would be facilitated by the effect of HDAC3i to reduce cortical tuning bandwidth by enabling accurate, precise, and discriminative encoding for acoustic frequency. Chapter 2 demonstrates that the frequency-specificity of memory for the rewarded tone-cue in a finer frequency discrimination task was indeed facilitated with HDAC3i treatment, but this behavior did not appear to be supported by narrower bandwidth tuning; instead, the threshold of sound-evoked activity was changed in cortical responses. These findings support that a behavioral function of HDAC3 inhibition during consolidation is indeed to increase the sensory specificity of memory, but can be achieved by engaging different, and even multiple forms of experience-dependent plasticity to support the sound-specific behavior. In Chapter 3, we use chronic cortical recordings to characterize the temporal dynamics of auditory cortical plasticity that emerges over the course of incremental discrimination training and find that auditory learning can modify tone-evoked responses within the first few training sessions, as predicted by early behavioral effects in Chapter 1. These early changes linked to the early training HDAC3-inhibitor treatment (as in Chapters 1 and 2) are likely initial substrates for long-lasting effects on auditory cortical plasticity and memory specificity observed even weeks later. Interestingly, behavioral effects of auditory cortical tuning bandwidth changes on memory specificity did not impact the associative strength of memory tested behaviorally with a discrimination reversal challenge, which highlights the identified forms of plasticity as neural substrates of specificity per se. Collectively, results from these experiments link behavioral evidence of memory specificity with unique forms of experience-dependent plasticity in auditory cortex that emerge quickly and persist over long periods of time. That multiple forms of learning-related plasticity support precise and accurate auditory memory in the auditory cortex suggest that some characteristics of memory – here, specificity – can be represented in sensory systems. Sensory systems may adopt different neural coding strategies that depend on the stimulus and task type to encode the particular stimulus features that demand attention and action as a function of their associative links to behaviorally significant outcomes.