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

Abstract

Summary 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.

Cellular Classes in the Human Brain Revealed In Vivo by Heartbeat-Related Modulation of the Extracellular Action Potential Waveform

“…Eleven patients were implanted with hybrid depth electrodes for monitoring the source of intractable epilepsy (for details, see Carlson et al, 2018;Rutishauser et al, 2010). In addition to these recordings, we recorded electrophysiological signals intraoperatively from 20 patients with motor disorders being implanted with deep brain stimulation (DBS) electrodes (for details, see Kami nski et al, 2018).…”

“…In addition to these recordings, we recorded electrophysiological signals intraoperatively from 20 patients with motor disorders being implanted with DBS electrodes (for details, see Kami nski et al, 2018). During each intraoperative session, two microelectrodes were placed to map the transitions through different brain regions and to identify the target for the DBS electrode.…”

“…Microelectrode recordings targeted the subthalamic nucleus, the substantia nigra, or the putamen. Target locations were determined stereotaxically based on preoperative 3T T1-and T2-weighted MRI scans co-registered with preoperative CT scans (Kami nski et al, 2018). Broadband (0.1 Hz to 32 kHz) electrophysiological signals were recorded intraoperatively at a 40 kHz sampling rate using a NeuroOmega system (Alpha Omega, Nazareth Il.).…”

Reward Prediction Error and Declarative Memory

“…Indeed, episodic memory is enhanced when multimodal (audiovisual) stimuli are synchronously presented in theta phase; with stronger theta phase synchronization predicting better memory performance [44,45]. Dopaminergic midbrain neurons have also been found to phase-lock to (cortical) theta during encoding, with stronger phase-locking during subsequently remembered (versus forgotten) memoranda [46]. Thus, it is possible that RPEs (via neuromodulatory signaling) increase theta synchrony, which subsequently allows the relevant brain areas to "glue" the episode together more efficiently Whereas dopaminergic RPEs likely support non-declarative learning via basal ganglia pathways, dopaminergic RPEs may support declarative memory via hippocampus [49].…”

Intrinsically regulated learning is modulated by synaptic dopamine availability

“…Growing evidence both from animal and human studies support the notion that midbrain dopaminergic neurons of the substantia nigra/ventral tegmental area complex (SN/VTA), along with the the ventral striatum (VS) and the hippocampus (HP), form a functional loop (the SN/VTA-HP loop) in the service of learning and memory (Lisman and Grace, 2005;Goto and Grace, 2005;Lisman et al, 2011;Shohamy and Adcock, 2010;Kaminski et al, 2018). In the downward arm of the circuit, signals are sent from the HP to the SN/VTA through the VS, which is thought to integrate affective, motivational, and goaldirected information into the loop (Lisman and Grace, 2005;Goto and Grace, 2005).…”