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

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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.