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Interactions between these regions have been studied indirectly using functional MRI, but the bases for interregional communication at a cellular level remain poorly understood. Here, we evaluate the hypothesis that oscillatory currents in the hippocampus synchronize the firing of neurons both within and outside the hippocampus. We recorded extracellular spikes from 1854 single- and multi-units simultaneously with hippocampal local field potentials (LFPs) in 28 neurosurgical patients who completed virtual navigation experiments. A majority of hippocampal neurons phase-locked to oscillations in the slow (2\u20134 Hz) or fast (6\u201310 Hz) theta bands, with a significant subset exhibiting nested slow theta \u00d7 beta frequency (13\u201320 Hz) phase-locking. Outside of the hippocampus, phase-locking to hippocampal oscillations occurred only at theta frequencies and primarily among neurons in the entorhinal cortex and amygdala. Moreover, extrahippocampal neurons phase-locked to hippocampal theta even when theta did not appear locally. These results indicate that spike-time synchronization with hippocampal theta is a defining feature of neuronal activity in the hippocampus and structurally connected MTL regions. Theta phase-locking could mediate flexible communication with the hippocampus to influence the content and quality of memories.<\/jats:p>","DOI":"10.7554\/elife.85753","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T06:15:14Z","timestamp":1704780914000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.85753","source":"Crossref","is-referenced-by-count":20,"title":["MTL neurons phase-lock to human hippocampal theta"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8667-031X","authenticated-orcid":true,"given":"Daniel R","family":"Schonhaut","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00b30xv10","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania","place":["Philadelphia, United 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