Auditory training remodels hippocampus-related memory in adult rats.

Consequences of perceptual training, such as improvements in discriminative ability, are highly stimulus and task specific. Therefore, most studies on auditory training-induced plasticity in adult brain have focused on the sensory aspects, particularly on functional and structural effects in the auditory cortex. Auditory training often involves, other than auditory demands, significant cognitive components. Yet, how auditory training affects cognition-related brain regions, such as the hippocampus, remains unclear. Here, we found in female rats that auditory cue-based go/no-go training significantly improved the memory-guided behaviors associated with hippocampus. The long-term potentiations of the trained rats recorded in vivo in the hippocampus were also enhanced compared with the naïve rats. In parallel, the phosphorylation level of calcium/calmodulin-dependent protein kinase II and the expression of parvalbumin-positive interneurons in the hippocampus were both upregulated. These findings demonstrate that auditory training substantially remodels the processing and function of brain regions beyond the auditory system, which are associated with task demands.

Pairing with Enriched Sound Exposure Restores Auditory Processing Degraded by an Antidepressant.

Antidepressants, while effective in treating depression and anxiety disorders, also induce deficits in sensory (particularly auditory) processing, which in turn may exacerbate psychiatric symptoms. How antidepressants cause auditory signature deficits remains largely unknown. Here, we found that fluoxetine-treated adult female rats were significantly less accurate when performing a tone-frequency discrimination task compared with age-matched control rats. Their cortical neurons also responded less selectively to sound frequencies. The degraded behavioral and cortical processing was accompanied by decreased cortical perineuronal nets, particularly those wrapped around parvalbumin-expressing inhibitory interneurons. Furthermore, fluoxetine induced critical period-like plasticity in their already mature auditory cortices; therefore, a brief rearing of these drug-treated rats under an enriched acoustic environment renormalized auditory processing degraded by fluoxetine. The altered cortical expression of perineuronal nets was also reversed as a result of enriched sound exposure. These findings suggest that the adverse effects of antidepressants on auditory processing, possibly because of a reduction in intracortical inhibition, can be substantially alleviated by simply pairing drug treatment with passive, enriched sound exposure. They have important implications for understanding the neurobiological basis of antidepressant effects on hearing and for designing novel pharmacological treatment strategies for psychiatric disorders.SIGNIFICANCE STATEMENT Clinical experience suggests that antidepressants adversely affect sensory (particularly auditory) processing, which can exacerbate patients' psychiatric symptoms. Here, we show that the antidepressant fluoxetine reduces cortical inhibition in adult rats, leading to degraded behavioral and cortical spectral processing of sound. Importantly, fluoxetine induces a critical period-like state of plasticity in the mature cortex; therefore, a brief rearing under an enriched acoustic environment is sufficient to reverse the changes in auditory processing caused by the administration of fluoxetine. These results provide a putative neurobiological basis for the effects of antidepressants on hearing and indicate that antidepressant treatment combined with enriched sensory experiences could optimize clinical outcomes.

Environmental noise degrades hippocampus-related learning and memory.

The neural mechanisms underlying the impacts of noise on nonauditory function, particularly learning and memory, remain largely unknown. Here, we demonstrate that rats exposed postnatally (between postnatal days 9 and 56) to structured noise delivered at a sound pressure level of ∼65 dB displayed significantly degraded hippocampus-related learning and memory abilities. Noise exposure also suppressed the induction of hippocampal long-term potentiation (LTP). In parallel, the total or phosphorylated levels of certain LTP-related key signaling molecules in the synapses of the hippocampus were down-regulated. However, no significant changes in stress-related processes were found for the noise-exposed rats. These results in a rodent model indicate that even moderate-level noise with little effect on stress status can substantially impair hippocampus-related learning and memory by altering the plasticity of synaptic transmission. They support the importance of more thoroughly defining the unappreciated hazards of moderately loud noise in modern human environments.

Developmental Exposure to Bisphenol a Degrades Auditory Cortical Processing in Rats.

Developmental exposure to bisphenol A (BPA), an endocrine-disrupting contaminant, impairs cognitive function in both animals and humans. However, whether BPA affects the development of primary sensory systems, which are the first to mature in the cortex, remains largely unclear. Using the rat as a model, we aimed to record the physiological and structural changes in the primary auditory cortex (A1) following lactational BPA exposure and their possible effects on behavioral outcomes. We found that BPA-exposed rats showed significant behavioral impairments when performing a sound temporal rate discrimination test. A significant alteration in spectral and temporal processing was also recorded in their A1, manifested as degraded frequency selectivity and diminished stimulus rate-following by neurons. These post-exposure effects were accompanied by changes in the density and maturity of dendritic spines in A1. Our findings demonstrated developmental impacts of BPA on auditory cortical processing and auditory-related discrimination, particularly in the temporal domain. Thus, the health implications for humans associated with early exposure to endocrine disruptors such as BPA merit more careful examination.

Degraded cortical temporal processing in the valproic acid-induced rat model of autism.

Hearing disorders, such as abnormal speech perception, are frequently reported in individuals with autism. However, the mechanisms underlying these auditory-associated signature deficits in autism remain largely unknown. In this study, we documented significant behavioral impairments in the sound temporal rate discrimination task for rats prenatally exposed to valproic acid (VPA), a well-validated animal model for studying the pathology of autism. In parallel, there was a large-scale degradation in temporal information-processing in their primary auditory cortices (A1) at both levels of spiking outputs and synaptic inputs. Substantially increased spine density of excitatory neurons and decreased numbers of parvalbumin- and somatostatin-labeled inhibitory inter-neurons were also recorded in the A1 after VPA exposure. Given the fact that cortical temporal processing of sound is associated with speech perception in humans, these results in the animal model of VPA exposure provide insight into a possible neurological mechanism underlying auditory and language-related deficits in individuals with autism.