Neurophysiological, structural, and molecular alterations in the prefrontal and auditory cortices following noise-induced hearing loss

• Published in: Neurobiology of disease 2024-10, Vol.200, p.106619, Article 106619
• Main Authors: Hayes, Sarah H., Patel, Salonee V., Arora, Parinita, Zhao, Lin, Schormans, Ashley L., Whitehead, Shawn N., Allman, Brian L.
• Format: Article
• Language: English
• Subjects: 40-Hz auditory steady state response; Auditory cortex; Dendritic structure; Gamma phase coherence; Hearing loss; Noise exposure; Prefrontal cortex; Protein expression
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2024.106619

It is well established that hearing loss can lead to widespread plasticity within the central auditory pathway, which is thought to contribute to the pathophysiology of audiological conditions such as tinnitus and hyperacusis. Emerging evidence suggests that hearing loss can also result in plasticity within brain regions involved in higher-level cognitive functioning like the prefrontal cortex; findings which may underlie the association between hearing loss and cognitive impairment documented in epidemiological studies. Using the 40-Hz auditory steady state response to assess sound-evoked gamma oscillations, we previously showed that noise-induced hearing loss results in impaired gamma phase coherence within the prefrontal but not the auditory cortex. To determine whether region-specific structural or molecular changes accompany this differential plasticity following hearing loss, in the present study we utilized Golgi-Cox staining to assess dendritic organization and synaptic density, as well as Western blotting to measure changes in synaptic signaling proteins in these cortical regions. We show that following noise exposure, impaired gamma phase coherence within the prefrontal cortex is accompanied by alterations in pyramidal cell dendritic morphology and decreased expression of proteins involved in GABAergic (GAD65) and glutamatergic (NR2B) neurotransmission; findings that were not observed in the auditory cortex, where gamma phase coherence remained unchanged post-noise exposure. In contrast to the noise-induced effects we observed in the prefrontal cortex, plasticity in the auditory cortex was characterized by an increase in NR2B suggesting increased excitability, as well as increases in the synaptic proteins PSD95 and synaptophysin within the auditory cortex. Overall, our results highlight the disparate effect of noise-induced hearing loss on auditory and higher-level brain regions as well as potential structural and molecular mechanisms by which hearing loss may contribute to impaired cognitive and sensory functions mediated by the prefrontal and auditory cortices. •Differential plasticity occurs in auditory and prefrontal cortex after hearing loss.•Hearing loss impairs gamma phase coherence in prefrontal but not auditory cortex.•Prefrontal cortex shows altered pyramidal cell dendritic structure after hearing loss.•Hearing loss decreases GAD65 and NR2B expression in prefrontal cortex.•Auditory cortex shows an increase in NR2B expression following h