A perfusate collected from tetanized donor slices of rat olfactory cortex was separated by ultrafiltration into fractions containing substances with molecular weights of less than and greater than 50 kDal. Each fraction was separately tested on recipient slices. The fraction with substances of greater than 50 kDal elicited long-term depression of focal potentials in recipient slices. The fraction with substances of less than 50 kDal mainly induced activation. The chemical nature of the factors released during tetanization was studied by treating the high-molecular-weight fraction with immobilized trypsin; after proteolytic treatment this fraction produced a qualitatively different response in recipient slices, suggesting that the active factors were polypeptides. These data indicate that donor slice cells release a set of neurohumoral substances, probably polypeptides, during tetanization, which are involved in the modulation of synaptic plasticity.

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