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Novelty-Sensitive Dopaminergic Neurons in the Human Substantia Nigra Predict Success of Declarative Memory Formation

Kamiński J, Mamelak AN, Birch K, Mosher CP, Tagliati M, Rutishauser U                                                              Publication      

Current Biology (2018)


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.

(A) It has been proposed that the dopaminergic system and the hippocampus form a multisynaptic loop that starts with a hippocampal novelty signal that transiently excites dopaminergic neurons in the SN/VTA, which in turn leads to strengthening of hippocampal plasticity through the activation of hippocampal dopamine receptors.
(B) The task. Top: screens presented to the subjects during an example trial. Bottom: the lengths of time for which each screen was shown.
(C) Percent of all recorded SN cells that showed a significant increase in firing rate to novel images (n = 11) or familiar images (n = 6)
(D) Example of a memory selective cell. Top: PSTH (bin size, 400 ms; step size, 1 ms). Shaded areas represent ± SEM across trials. Middle: periods of significance marked in green (p < 0.05, permuted t test; corrected for multiple comparisons using a cluster-size correction). Bottom: raster plot with trials sorted according to image novelty/familiarity. The inset shows the mean extracellular waveform ± SEM of all spikes associated with this cell.
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