TMS effects on circuit plasticity and drug seeking in mice - Diversity Supplement

项目摘要/摘要 在美国，吸毒成瘾是导致发病率和死亡率的主要原因。中国人的阿片成瘾 特别是已经成为一种流行病，史无前例的过量死亡，其中一半是 由芬太尼引起。我们治疗阿片成瘾的曲目非常有限，在这方面的进展 寻找有效的治疗方法已经停滞不前。经颅磁刺激(TMS)作为一种 一种潜在的治疗工具；目前FDA批准它用于抑郁症和尼古丁 无序。这项建议将在阿片类药物的小鼠模型中调查TMS的使用参数 上瘾。通过磁脉冲，TMS非侵入性地激活大脑皮质神经元。 靶区，导致全脑变化。然而，有几个问题仍然没有得到回答。 包括TMS的间歇性Theta-Burst刺激(ITBS)是否会导致持续时间延长 靶区以外下游回路的变化，以及TMS如何影响远端大脑 由TMS逆序激活的电路。本提案将使用TMS解决这些问题 在小鼠模型中的嗅球。假设是嗅球的ITBS TMS 诱发可塑性变化，比高频刺激方案更明显 参与学习和奖励的下游回路，如梨状皮质和嗅觉 结节(腹侧纹状体的一部分)，不同的TMS方案也会引起逆行反应 远端环路的可塑性可能低于TMS的一些治疗效果。

Project Summary/Abstract Drug addiction is a leading cause of morbidity and mortality in the US. Opioid addiction in particular has become an epidemic with unprecedented overdose fatalities, half of which are caused by fentanyl. Our repertoire to treat opioid addiction is very limited, and the progress in finding effective treatments has stalled. Transcranial Magnetic Stimulation (TMS) is emerging as a potential therapeutic tool; it is currently FDA approved for depression and nicotine use disorder. This proposal will investigate the parameters of TMS use in a mouse model of opioid addiction. Through magnetic pulses, TMS non-invasively activates cortical neurons in the targeted area, resulting in brain-wide changes. However, several questions remain unanswered including whether intermittent Theta-Burst Stimulation (iTBS) with TMS induces long-lasting changes in downstream circuits beyond the targeted area, and how TMS affects distal brain circuits antidromically activated by TMS. This proposal will address these questions using TMS of the olfactory bulb in a mouse model. The hypothesis is that iTBS TMS of the olfactory bulb induces plasticity changes, more pronounced than high frequency stimulation protocols, in downstream circuits involved in learning and reward such as the piriform cortex and olfactory tubercle (part of the ventral striatum), and that different TMS protocols also induce antidromic plasticity in distal circuits which could underly some of the therapeutic effects of TMS.