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However, manipulating specific circuits within complex brain areas poses significant challenges due to heterogenous cell types with varying inherent sonosensitivity. Building on previous gas\u2010vesicle\u2010assisted ultrasound neuromodulation studies, we investigate an in vivo nanobubble\u2010enhanced sonogenetic strategy, termed mechanogenetics, for circuit\u2010level neural modulation. Application of this approach to distinct brain regions increased electromyography responses following motor\u2010cortex stimulation and enhanced neural activity in deep\u2010brain regions. Importantly, mechanogenetics enables us to modulate neural circuits controlling feeding behavior by specifically stimulating the mouse lateral hypothalamus (LH), with minimal disturbance in adjacent areas. The observed mechanogenetically\u2010induced decreases in feeding behavior were further found to be mediated by LH\u2010glutamatergic inputs to the ventral tegmental area. Furthermore, assessments of neural integrity, inflammation, and apoptosis support biosafety under the tested conditions. These findings demonstrate the feasibility of applying mechanogenetics to a behaviorally relevant deep neural circuit and provide a framework for localized, genetically targeted ultrasound neuromodulation.<\/jats:p>","DOI":"10.1002\/advs.78177","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:16:13Z","timestamp":1791350173000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Mechanogenetics to Modulate Specific Deep Neural Circuits"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9718-6539","authenticated-orcid":false,"given":"Xuandi","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering The Hong Kong Polytechnic University  Hung Hom Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of 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