Reversing Synchronized Brain Circuits with Targeted Auditory-Somatosensory Stimulation to Treat Phantom Percepts

摘要 耳蜗背核（DCN）通过电路整合听觉和体感信息， 调节回路的主要输出神经元，梭形细胞的活动。梭形细胞接受 躯体感觉信息通过其顶端树突上的突触传递， 树突当体感激活与声音相结合时，电路可以得到加强， 根据双峰刺激的顺序减弱。这个过程被称为刺激时间依赖性 可塑性在幻听或耳鸣的情况下，DCN电路被加强， 增加梭形细胞的放电频率和同步性。本建议旨在研究 通过实施双峰声音+ 电刺激范例来改变正常和病理条件下的电路。动物和人类 将进行研究以优化削弱电路所需的刺激参数/剂量， 从而改善病理状态。这将最终导致神经疾病的治疗， 过度活跃或超同步回路，如耳鸣或帕金森氏病。

Abstract The dorsal cochlear nucleus (DCN) integrates auditory and somatosensory information through circuitry that modulates activity of the principal output neurons of the circuit, the fusiform cells. Fusiform cells receive somatosensory information via synapses on their apical dendrites and acoustic information via their basal dendrites. When somatosensory activation is combined with sound, the circuit can be strengthened or weakened depending on the order of the bimodal stimuli. This process is called stimulus timing dependent plasticity. In the condition of phantom sound perception, or tinnitus, the DCN circuitry is strengthened to increase the firing rates and synchrony of fusiform cells. This proposal seeks to investigate the effects of manipulations on the circuitry of this first auditory brainstem nucleus by implementing a bimodal sound + electrical stimulus paradigm to alter the circuit in normal and pathological conditions. Animal and human studies will be conducted to optimize the stimulation parameters/dosages necessary to weaken the circuit and thus ameliorate the pathological condition. This will ultimately lead to treatments for neural disorders involving hyperactive or hyper synchronous circuits such as those identified for tinnitus or Parkinson's disease.