NSF Award
1554105
Memory disorders affect millions of Americans today. Despite decades of work, we have little ability to prevent, improve or treat such memory disorders. With the support of the National Science Foundation, Dr. Ueli Rutishauser and colleagues are investigating how humans form, store, and retrieve memories. The research supported by this CAREER award is to observe the electrical activity of brain cells in the hippocampus, an area essential for the formation of new memories. This research is performed with human patients who are undergoing surgery to treat epilepsy. To localize seizures, these patients are implanted with small wires in different parts of their brain, which allows researchers to investigate the human nervous system at the cellular level. Using this technique, we will investigate how human brain cells change when new memories are formed. Specifically, we will test whether the formation of new memories is dependent on a brain rhythm called the "theta oscillation", and if disruptions of this rhythm lead to poor memory. Critically, theta oscillations can be changed by electrical stimulation, which offers a potential technique to improve memory. Through education, teaching, and mentoring, this CAREER award will enable new researchers and organizations to take advantage of the extremely valuable opportunities for basic research on the human nervous system presented by intracranial electrophysiology. <br/><br/>The research objective of this CAREER award is to investigate the neural mechanisms of human declarative memory at the level of individual neurons and circuits. We work with patients implanted with micro-wire electrodes who volunteer to participate in this research. The objective is to understand how the activity of networks of neurons is coordinated such that their collective action results in plasticity and long-term memories. We test the hypothesis that hippocampal theta oscillations mediate this process by combining human single-neuron recordings, behavioral testing, electrical stimulation, and computational modelling. This approach will allow us to assess the role and necessity of oscillations for the formation of human memories and thereby demonstrate the role of a specific oscillation in human cognition. We study i) how the activity of two distinct functional types of hippocampal neurons that we identified (visual and memory selective) are modulated by the theta rhythm; ii) how modulation of theta oscillations by shifts in spatial attention impacts individual neurons; and iii) whether there is a causal link between theta oscillations and memory strength. This study could provide, for the first time, a link between the cellular mechanisms of plasticity, oscillations, and human memory. The educational objective is to closely involve students in all aspects of the research, and to incorporate research results into classes, workshops and a K-12 outreach program. The resulting methods, tools, and datasets will be publicly released.
