Hearing loss often results in tinnitus and auditory cortical map changes, leading to the prevailing view that the phantom perception is associated with cortical reorganization. However, we show here that tinnitus is mediated by a cortical area lacking map reorganization. High-frequency hearing loss results in two distinct cortical regions: a sensory-deprived region characterized by a decrease in inhibitory synaptic transmission and a normal hearing region showing increases in inhibitory and excitatory transmission and map reorganization. Hearing-lesioned animals displayed tinnitus with a pitch in the hearing loss range. Furthermore, drugs that enhance inhibition, but not those that reduce excitation, reversibly eliminated the tinnitus behavior. These results suggest that sensory deprivation-induced homeostatic down-regulation of inhibitory synapses may contribute to tinnitus perception. Enhancing sensory input through map reorganization may plausibly alleviate phantom sensation.

Hearing loss is a major risk factor for tinnitus, hyperacusis, and central auditory processing disorder. Although recent studies indicate that hearing loss causes neuroinflammation in the auditory pathway, the mechanisms underlying hearing loss–related pathologies are still poorly understood. We examined neuroinflammation in the auditory cortex following noise-induced hearing loss (NIHL) and its role in tinnitus in rodent models. Our results indicate that NIHL is associated with elevated expression of proinflammatory cytokines and microglial activation—two defining features of neuroinflammatory responses—in the primary auditory cortex (AI). Genetic knockout of tumor necrosis factor alpha (TNF-α) or pharmacologically blocking TNF-α expression prevented neuroinflammation and ameliorated the behavioral phenotype associated with tinnitus in mice with NIHL. Conversely, infusion of TNF-α into AI resulted in behavioral signs of tinnitus in both wild-type and TNF-α knockout mice with normal hearing. Pharmacological depletion of microglia also prevented tinnitus in mice with NIHL. At the synaptic level, the frequency of miniature excitatory synaptic currents (mEPSCs) increased and that of miniature inhibitory synaptic currents (mIPSCs) decreased in AI pyramidal neurons in animals with NIHL. This excitatory-to-inhibitory synaptic imbalance was completely prevented by pharmacological blockade of TNF-α expression. These results implicate neuroinflammation as a therapeutic target for treating tinnitus and other hearing loss–related disorders.

Thermal imaging provides information regarding the general condition of the human body and facilitates the diagnosis of various diseases. Heat therapy or thermotherapy can help in the treatment of injuries to the skin tissue. Here, we report a wearable thermal patch with dual functions of continuous skin temperature sensing and thermotherapy for effective self-care treatment. This system consists of a graphene-based capacitive sensor, a graphene thermal pad, and a flexible readout board with a wireless communication module. The wearable sensor continuously monitors the temperature variation over a large area of the skin (3 × 3cm ² ) with high resolution and sensitivity and performs thermotherapy via the graphene-based heater mounted at the bottom of the device. Animal studies prove that the proposed system can be used to diagnose various diseases. This technology could be useful in the development of convenient and wearable health care devices.

Significance: It has generally been thought that CA1 cells form only negligible connections with each other along the longitudinal axis of the hippocampus. But if CA1 cells were interconnected in an effective autoassociational network, this information would add a critical new dimension to our understanding of cellular processing within this structure. Here, we report the existence of a well-organized, longitudinally projecting synaptic network among CA1 pyramidal neurons. We further show that synapses of this network are capable of supporting synaptic plasticity, including long-term potentiation, and a short-term memory mechanism called “dendritic hold and read.” These observations will contribute to the construction of more realistic models of hippocampal information processing in behavior, memory, and other cognitive functions.

Partial hearing loss often results in enlarged representations of the remaining hearing frequency range in primary auditory cortex (AI). Recent studies have implicated certain types of synaptic plasticity in AI map reorganization in response to transient and long-term hearing loss. How changes in neuronal excitability and morphology contribute to cortical map reorganization is less clear. In the present study, we exposed adult rats to a 4-kHz tone at 123 dB, which resulted in increased thresholds over their entire hearing range. The threshold shift gradually recovered in the lower-frequency, but not the higher-frequency, range. As reported previously, two distinct zones were observed 10 days after the noise exposure, an enlarged lower-characteristic frequency (CF) zone displaying normal threshold and enhanced cortical responses and a higher-CF zone showing higher threshold and a disorganized tonotopic map. Membrane excitability of layer II/III pyramidal neurons increased only in the higher-CF, but not the lower-CF, zone. In addition, dendritic morphology and spine density of the pyramidal neurons were altered in the higher-CF zone only. These results indicate that membrane excitability and neuronal morphology are altered by long-term, but not transient, threshold shift. They also suggest that these changes may contribute to tinnitus but are unlikely to be involved in map expansion in the lower-CF zone.

Transient potassium current channels (I_A channels), which are expressed in most brain areas, have a central role in modulating feedforward and feedback inhibition along the dendroaxonic axis. Loss of the modulatory channels is tightly associated with a number of brain diseases such as Alzheimer’s disease, epilepsy, fragile X syndrome (FXS), Parkinson’s disease, chronic pain, tinnitus, and ataxia. However, the functional significance of I_A channels in these diseases has so far been underestimated. In this review, we discuss the distribution and function of I_A channels. Particularly, we posit that downregulation of I_A channels results in neuronal (mostly dendritic) hyperexcitability accompanied by the imbalanced excitation and inhibition ratio in the brain’s networks, eventually causing the brain diseases. Finally, we propose a potential therapeutic target: the enhanced action of I_A channels to counteract Ca²⁺-permeable channels including NMDA receptors could be harnessed to restore dendritic excitability, leading to a balanced neuronal state.