Novelty-Sensitive Dopaminergic Neurons in the Human Substantia Nigra Predict Success of Declarative Memory Formation
Abstract
The encoding of information into long-term declarative memory is facilitated by dopamine. This process depends on hippocampal novelty signals, but it remains unknown how midbrain dopaminergic neurons are modulated by declarative-memory-based information. We recorded individual substantia nigra (SN) neurons and cortical field potentials in human patients performing a recognition memory task. We found that 25% of SN neurons were modulated by stimulus novelty. Extracellular waveform shape and anatomical location indicated that these memory-selective neurons were putatively dopaminergic. The responses of memory-selective neurons appeared 527 ms after stimulus onset, changed after a single trial, and were indicative of recognition accuracy. SN neurons phase locked to frontal cortical theta-frequency oscillations, and the extent of this coordination predicted successful memory formation. These data reveal that dopaminergic neurons in the human SN are modulated by memory signals and demonstrate a progression of information flow in the hippocampal-basal ganglia-frontal cortex loop for memory encoding.
Additional Information
© 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Open access funded by National Institutes of Health. Received: November 6, 2017; Received in revised form: February 13, 2018; Accepted: March 13, 2018; Published: April 12, 2018. We gratefully acknowledge the willingness of our patients to participate in this study. We thank the Cedars-Sinai operating room staff for their assistance, Robert Zavala and Lori Scheinost for technical neurophysiology support, and Jeffrey Wertheimer for neuropsychological evaluation of patients. We thank Ralph Adolphs and all members of the Rutishauser Laboratory for discussion. This study was made possible by seed funding from the Pfeiffer Foundation and was later also supported by NIH NINDS ( U01NS098961 ), an NSF CAREER Award ( BCS-1554105 ), and the McKnight Endowment Fund for Neuroscience (all to U.R.). Author Contributions: U.R. and J.K. designed the experiment. J.K., U.R., K.B., and C.P.M. performed experiments. J.K. and U.R. performed analysis. A.N.M. and K.B. performed surgery. M.T. provided patient care. J.K., A.N.M., and U.R. wrote the paper. All of the authors discussed the results at all stages of the project. The authors declare no competing interests.Attached Files
Published - 1-s2.0-S0960982218303531-main.pdf
Accepted Version - nihms968703.pdf
Supplemental Material - mmc1.pdf
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Additional details
- PMCID
- PMC5973539
- Eprint ID
- 85777
- Resolver ID
- CaltechAUTHORS:20180412-102930676
- Pfeiffer Foundation
- U01NS098961
- NIH
- BCS-1554105
- NSF
- McKnight Foundation
- Created
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2018-04-12Created from EPrint's datestamp field
- Updated
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2021-11-15Created from EPrint's last_modified field