REVERSIBLE DISRUPTION OF MEMORY

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Work in the previous support period led to a finding that electrical stimulation of the medial temporal lobe of monkeys during the delay period of a delayed matching-to-sample task was highly disruptive of performance if only a few images were repeatedly reused. The identical stimulation was only mildly disruptive if fresh images were used for each trial. In memory tasks with human subject, the use of repeated images leads to a strategy of active rehearsal during the delay period. In monkeys, the use of repeated images is a key to inducing the so- called delay activity. This is an elevated discharge rate in neurons usually lasting throughout the delay period, with different neurons selectively active for different stimuli. Thus, the activity across the population of neurons encodes a memory of that which is to-be- remembered. The delay activity appears like a neuronal version of continuous rehearsal, and is an excellent candidate for the neural embodiment of memory during the delay under these conditions. The fascination with this delay activity is that it may be our best model for the everyday human working memory which is the substrate for thought. The evidence that delay activity is the holder of the memory is, however, indirect. The purpose of the current proposal is to test that hypothesis directly. This will be done by using electrical stimulation which is known to disrupt that delay activity (see Preliminary Studies). If delay activity of neurons is the carrier of the memory then disruption of the delay activity should disrupt the behavioral memory. The contribution of this project is aimed directly at a prominent candidate neuronal mechanism of memory. Its clinical relevance is not immediate but could nonetheless be profound since a full understanding of the mnemonic circuitry should have a major impact on the important - and with the aging population - growing health problems involving memory.