Nature 339, 215 - 218 (18 May 1989); doi:10.1038/339215a0

Associative long-term depression in the hippocampus induced by hebbian covariance

Patric K. Stanton^* & Terrence J. Sejnowski^*

Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA
^* Present addresses: Departments of Neuroscience and Neurology, Albert Einstein College of Medicine, 1410 Pelham Parkway South, Bronx, New York 10461, USA (P.K.S.); Computational Neurobiology Laboratory, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, California 92037, and Department of Biology, University of California at San Diego, La Jolla, California 92093, USA (T.J.S.).

A BRIEF, high-frequency activation of excitatory synapses in the hippocampus produces a long-lasting increase in synaptic strengths called long-term potentiation (LTP)1. A test input, which by itself does not have a long-lasting effect on synaptic strengths, can be potentiated through association when it is activated at the same time as a separate conditioning input2–4.Neural network modelling studies have also predicted that synaptic strengths should be weakened when test and conditioning inputs are anti-correlated^5–8. Evidence for such heterosynaptic depression in the hippocampus has been found for inputs that are inactive^2,9 or weakly active³ during the stimulation of a conditioning input, but this depression does not depend on any pattern of test input activity and does not seem to last as long as LTP. We report here an associative long-term depression (LTD) in field CA1 that is produced when a low-frequency test input is negatively correlated in time with a high-frequency conditioning input. LTD of synaptic strength is also produced by activating presynaptic terminals while a postsy-naptic neuron is hyperpolarized. This confirms theoretical predictions⁸ that the mechanism for associative LTD is homosynaptic and follows a hebbian covariance rule⁷.

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