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The hippocampus (HC) plays vital roles in learning and memory and is especially susceptible to the pathological insults imposed by sleep deprivation (SD). While SD disrupts neuronal network signaling and triggers inflammatory processes, the impact of SD on metabolism within the HC presently remains poorly understood. In this study, we assessed the progressive and cumulative effects of partial SD in the live mouse HC CA1 region using two-photon microscopy. Using a custom-designed implantable cannula enabling direct HC visualization and administration of dyes and pharmacological agents directly to HC tissue, we longitudinally monitored spontaneous neuronal activity and partial pressure of oxygen (pO\u2082) within HC CA1 tissue before and during a 7-day period of partial SD and after a 7-day period of recovery. Our results revealed a progressive decline in spontaneous neural activity, alongside sustained elevation in tissue pO\u2082 during the 7-day partial SD period. Notably, after 7 days of recovery, neuronal activity did not return to baseline, and tissue oxygenation continued to increase. Our findings emphasize chronic SD\u2019s cumulative and enduring impairments to neuronal function and metabolism in the HC and reveal uncoupling between metabolic and functional recovery that outlasts the sleep restriction period.<\/jats:p>","DOI":"10.64898\/2026.09.25.754485","type":"posted-content","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:35:13Z","timestamp":1790886913000},"source":"Crossref","is-referenced-by-count":0,"title":["Partial sleep deprivation diminishes and uncouples neuronal activity and energy metabolism in the live mouse hippocampus"],"prefix":"10.64898","author":[{"given":"Zhengyi","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Bioengineering, Northeastern University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Mai","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Northeastern University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Cardenas-Rivera","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Northeastern University, Boston, MA, USA"},{"name":"Centro de Investigaci\u00f3n en Bioingenier\u00eda, Universidad de Ingenier\u00eda y Tecnolog\u00eda (UTEC), Lima, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Northeastern University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuntao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Northeastern University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Northeastern University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physics, Northeastern University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan Q.","family":"Spring","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Northeastern University, Boston, MA, USA"},{"name":"Department of Physics, Northeastern University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad A","family":"Yaseen","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Northeastern University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100610351134000_2026.09.25.754485v1.1","doi-asserted-by":"crossref","unstructured":"R. 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