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

摘要 耳蜗背核(DCN)通过以下回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 它们的躯体感觉信息通过突触在顶端树突上传递，而声学信息通过它们的基底突触传递。 树枝状结构。当体感激活与声音相结合时，电路可以得到加强或 根据双峰刺激的顺序而减弱。这一过程被称为刺激时序依赖 可塑性。在幻听或耳鸣的情况下，DCN电路被加强以 提高梭形细胞的放电频率和同步性。这项提案旨在调查 通过实施双峰Sound+对第一个听觉脑干核团的电路进行操纵 电刺激模式，以改变正常和病理条件下的电路。动物和人类 将进行研究以优化必要的刺激参数/剂量以削弱电路和 从而改善病理状态。这最终将导致对神经障碍的治疗，包括 过度活跃或过度同步的回路，如耳鸣或帕金森氏症。

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.