MTL neurons phase-lock to human hippocampal theta
- University of Pennsylvania, United States
- University of California, Los Angeles, United States
Abstract
Memory formation depends on neural activity across a network of regions, including the hippocampus and broader medial temporal lobe (MTL). 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 1,854 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 (2-4Hz) or fast (6-10Hz) theta bands, with a significant subset exhibiting nested slow theta x beta frequency (13-20Hz) 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.
Data availability
The data used in this study is publicly available for download from the Cognitive Electrophysiology Data Portal: http://memory.psych.upenn.edu/Electrophysiological_Data. This dataset includes de-identified, raw EEG data, spike-sorted unit data, and preprocessed phase-locking data. All data analysis code and JupyterLab notebooks can be freely downloaded at the public GitHub repositories: https://github.com/pennmem/SchoEtal24_eLife.
Article and author information
Author details
Daniel R Schonhaut
Funding
National Science Foundation Graduate Research Fellowship Program
- Daniel R Schonhaut
National Institutes of Health (1U01NS113198-01)
- Michael J Kahana
National Institute of Neurological Disorders and Stroke (R01-NS033221)
- Itzhak Fried
National Institute of Neurological Disorders and Stroke (R01-NS084017)
- Itzhak Fried
Deutsche Forschungsgemeinschaft (HE 8302/1-1)
- Nora A Herweg
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: All testing was completed under informed consent. Institutional review boards at the University of California, Los Angeles and the University of Pennsylvania approved all experiments. The number of the UCLA IRB protocol on which the Goldmine experiment was conducted is #10-000973.
Copyright
© 2024, Schonhaut et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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MTL neurons phase-lock to human hippocampal theta
eLife 13:e85753.
https://doi.org/10.7554/eLife.85753
Further reading
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- Neuroscience
When holding visual information temporarily in working memory (WM), the neural representation of the memorandum is distributed across various cortical regions, including visual and frontal cortices. However, the role of stimulus representation in visual and frontal cortices during WM has been controversial. Here, we tested the hypothesis that stimulus representation persists in the frontal cortex to facilitate flexible control demands in WM. During functional MRI, participants flexibly switched between simple WM maintenance of visual stimulus or more complex rule-based categorization of maintained stimulus on a trial-by-trial basis. Our results demonstrated enhanced stimulus representation in the frontal cortex that tracked demands for active WM control and enhanced stimulus representation in the visual cortex that tracked demands for precise WM maintenance. This differential frontal stimulus representation traded off with the newly-generated category representation with varying control demands. Simulation using multi-module recurrent neural networks replicated human neural patterns when stimulus information was preserved for network readout. Altogether, these findings help reconcile the long-standing debate in WM research, and provide empirical and computational evidence that flexible stimulus representation in the frontal cortex during WM serves as a potential neural coding scheme to accommodate the ever-changing environment.
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- Neuroscience
When navigating environments with changing rules, human brain circuits flexibly adapt how and where we retain information to help us achieve our immediate goals.
