Norbert J. Fortin - US grants

[unreadable] DESCRIPTION (provided by applicant): The first objective of this proposal is to characterize the firing patterns of hippocampal neurons associated with the disambiguation of memories for overlapping sequences of events, a critical feature of episodic memory. Single neuron activity and local field potentials in the CA1 and CAS regions will be recorded as rats perform a sequence disambiguation task. The relationships between the timing of spiking activity, phase of field potentials, and behavioral events will be analyzed to test specific predictions made from computational models. The second objective is to design a computational model that will incorporate these new findings to provide a detailed description of the neuronal mechanisms underlying sequence disambiguation, and to generate novel predictions for further analysis. The simulations will be constrained by the anatomy and physiology of the hippocampal region, and replicate the dimensions of the behavioral task. These results will add to our understanding of the mechanisms of hippocampal involvement in memory and consequently are fundamental to the study of disorders associated with dysfunction of the hippocampal system such as age-related memory disorder, Alzheimer's disease, schizophrenia, and autism. [unreadable] [unreadable] [unreadable]

Across the animal kingdom, episodic memory is a remarkable and highly adaptive ability. Episodic memory refers to the capacity to remember the events in one's life, including details about the specific location and time in which each experience occurred. Although it has been extensively studied, the brain basis of episodic memory remains poorly understood. This project addresses this important issue using a rodent model of episodic memory that focuses on the capacity to remember "when" specific events occurred (i.e., the order of events in a sequence and the time elapsed since an event occurred). More specifically, this project focuses on characterizing the role of the hippocampus and prefrontal cortex using high-precision techniques, such as localized brain inactivation and recording the electrical properties of single brain cells while rats are engaged in memory tasks. This project will identify the distinct roles that the hippocampus and the prefrontal cortex play in remembering when specific events occurred. Furthermore, the results will also likely shed light on how the two brain structures interact during information processing. A concurrent objective of this project is to develop effective educational practices and materials to promote early science training and awareness in groups underrepresented in science, and to support the development of young scientists in the laboratory and classroom. All developed educational tools will be openly shared on the lab website (http://fortinlab.bio.uci.edu) as well as online repositories of educational information such as Multimedia Educational Resource for Learning and Online Teaching (merlot.org) and OER Commons (oercommons.org).

The capacity to remember where and when certain events occur in one's life is of critical importance for survival and for participation in society function. This capacity, called episodic memory, is associated with the functions of the hippocampus and prefrontal cortex. Several neurological and psychiatric disorders involve dysfunctions in these brain regions. With support from the National Science Foundation, Dr. Norbert Fortin and colleague Dr. Craig Stark of the University of California at Irvine respectively will conduct an innovative series of parallel experiments in humans and rats, which are expected to contribute to a better understanding of the neural mechanisms underlying both normal and abnormal memory functions. This cross-species investigation will utilize a memory task that can be performed by humans and the rats, which is critical to make findings from animal studies relevant to our understanding of human memory and treatment of its deficit. This project will also provide an opportunity to develop effective educational practices and materials to promote early science training and awareness. These educational activities have a special emphasis on groups underrepresented in science (women and minority students), including a "Memory and the Brain" workshop that will be offered at schools with diverse student populations that also consistently perform below standard on the science portion of the California Standards Tests.

Although episodic memory has been extensively investigated, its neurobiological basis remains elusive. A major reason for this limited progress has been the inability to directly link evidence obtained from invasive techniques used in animal models (e.g. rodents) with that from non-invasive techniques used in humans because of differences in the demands of memory tasks used across these two species. Drs. Fortin and Stark will address this critical issue by using an integrated approach combining single-cell electrophysiological recordings in rats and BOLD fMRI in humans, to study episodic memory using their newly developed sequence memory task that can be performed by both rats and humans. This cross-species study will provide the first systematic examination of the functional correspondence between rodent and human sub-regions of the hippocampus and prefrontal cortex, known to play a critical role in memory and other higher-level cognitive functions. The knowledge gained from this study will significantly advance our understanding of the contribution of these brain structures to the memory for sequences of events, as well as of their fundamental role in learning and memory, executive functions, and decision-making.