Application) This project contributes to the Center's overall objectives by addressin g three fundamental concepts in the study of memory formation. The first concept is that memory traces are represented at the level of neuronal ensembles. In order to study memory formation at the neural level, the manner in which memory traces are represented in the activity of neuronal ensembles must be identified. This is essential when using molecular or behavioral approaches to manipulate memory formation in order to provide an observable neuronal correlate which reveals the effects of these manipulations. The neuronal ensemble level forms the interface between behavior and cellular mechanisms.
Specific Aims #1, #2, and #3 attempt to identify the basic network properties of memory trace formation in neocortical circuits by systematically examining the contributions of stimuli, experience, and behavior to alterations in ensemble activity. The impact of development will also be addressed by comparing the characteristics of neural memory formation in young and old animals. This work will be coordinated with related efforts by Mark Bear in Individual Project #6 to study mechanisms of neocortical synaptic plasticity. A second concept that is addressed by this project is that of distributed mnemonic function. Memory is a property of multiple brain structures that can be altered by experience. Therefore, to study the process of memory formation requires that the contributions of multiple brain areas are identified. By monitoring regions that have involvement in different types and aspects of memory formation we will begin to identify how multiple brain regions are coordinated in the larger process of memory formation. A specific hypothesis regarding a mnemonic process which involves coordination of multiple brain regions is that of hippocampal-neocortical memory consolidation.
Specific Aim #3 examines this particular interaction by simultaneously monitoring ensemble activity in the hippocampus and visual ncocortical areas during a behavioral memory task that requires the participation of both regions over the course of training. A specific focus of this investigation is the formation of memory representations for visual landmarks used during spatial navigation. This is contrasted with a visual memory task which does not require hippocampal involvement to allow separation of mnemonic effects from general task dependencies. The third concept is that of molecular and physiological mechanisms operating at both the cellular and network levels. By identifying the effects of altering plasticity within restricted regions of the brain on both behavior and ensemble activity, we can use these probes to determine the larger role of these cellular and molecular mechanisms in regulating the structure and process of memory information at the circuit and network level. This will be addressed in Specific Aim #4 in collaboration with Susumu Tonegawa.
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