Learning sequences is part of our daily lives, from getting dressed to remembering the event sequence of our day. Humans and other animals who develop mental disorders both have problems with many types of sequence learning. The objective of the proposed research is to understand how spatial sequences are learned and encoded by brain circuits so future experiments can measure deficits in brain coding of sequences that may underlie mental disorders. Currently, an animal model of how the normal brain accomplishes sequence learning does not exist and is necessary for understanding what goes wrong to produce deficits. Our laboratory has made progress towards developing a model of sequence learning by recording simultaneously from many neurons in the brain while rats learn to navigate to a series of spatial locations arranged around a circular arena. This task has allowed us to begin to understand how part of the brain, the hippocampus, encodes where the animal is in this spatial sequence; however, we do not yet know how the brain translates this information about position in the sequence into a motor response to navigate to the next reward location. Previous research suggests that the parietal cortex may translate an appropriate motor response for the current position in the sequence. Therefore, I will investigate the brain mechanism for translating information about position in a sequence to an appropriate motor response. In three different experiments, I will assess: a) the frames of reference (person centered vs world centered) that are used when spatial cues are encoded in the parietal cortex; b) activity patterns in the parietal cortex during sequence learning; c) contributions of the parietal cortex to encoding learned sequences (specifically, what happens when the parietal cortex is inhibited during particular portions of spatial sequence learning and memory). These initial experiments will provide a foundation for the neural basis of sequence learning so that we can assess deficits in brain coding of sequences that may underlie psychiatric disorders.

Public Health Relevance

Sequence learning is impaired in adults with a variety of mental disorders such as schizophrenia [e.g.; 46]; however; we know very little about normal sequence learning. [A parietial- hippocampal circuit in the brain] is dysfunctional in mental disorders such as schizophrenia [47] and mental disorders are increasingly being understood as disorders of circuits [48]; therefore; using current techniques [for functional dissection of braincircuits]; I will attempt to disassociate the roles of [these two regions of the brain] in spatial sequence learning to provide insight into the normal function of a circuit that is dysfunctional inhumans with mental disorders. Thus; the overall objective of this project is to understand how spatial sequences are learned so that [I can use] future experiments to measure changes in [brain circuits; learning and memory that are impaired] in humans with mental disorders.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F02A-J (20))
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Desmond, Nancy L
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University of California Irvine
United States
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