Abstract

How neuronal circuits enable complex behaviors such as learning and memory-based decision making remains poorly understood. Much of what we know about brain function has been inferred from studying the response of individual neurons in animal models. This leaves us unable to approach many important questions for lack of similar data in humans. We take advantage of rare neurosurgical procedures to record at single-cell resolution in behaving humans. I will review our experimental studies of individual neurons in the human hippocampus and amygdala during the formation and retrieval of declarative memories. These studies provide unique mechanistic insights into the relationship between neuronal activity, plasticity, memory formation, and the role of theta in coordinating large-scale neuronal dynamics. I will describe evidence for two distinct functional types of neurons in the human MTL : visually selective (VS) and memory selective (MS) neurons. VS neurons have highly specific sensory responses that occur early and irrespective of previous experience. MS neurons, on the other hand, are not visually selective, and are highly sensitive to previous experience and the internal brain state. Dynamically, the responses of these two sub-populations is orthogonal to each other. I will further describe evidence that MS and VS neurons are anatomically distinct and that their interaction is fundamental to the formation and retrieval of memories. These two functional sub-populations are a candidate for a circuit-level description of memory formation.