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

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. •Human substantia nigra (SN) neurons are modulated by stimulus novelty•Memory-selective neurons in substantia nigra are putatively dopaminergic•Phase locking of SN neurons to frontal oscillations predicts memory formation•Validates predictions of Lisman and Grace’s VTA/SN-hippocampus loop model in humans Kamiński et al. show that human substantia nigra neurons are modulated by stimulus novelty and that phase locking of these neurons to frontal cortical oscillations predicts memory formation. These findings provide direct single-neuron evidence for the engagement of the dopamine system in human declarative memory formation.