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Using the model of long-term posttetanic potentiation (LTP) in slices of the olfactory cortex of rat brain, we have tested a hypothesis according to which activation of nerve cells results in a release of neuromodulatory factors into extracellular space; these factors, diffusing over significant distances, are capable of synchronously modifying the initial reactivity of neuronal populations. Using the technique of bioassay, i.e., transfer of perfusate from the tetanized donor slice to the recipient slice, in combination with pharmacological and neurochemical techniques, we found that in response to excitation, the cells of olfactory cortex slices secrete peptides. This observation confirms the above hypothesis. The spectrum of released peptides changes depending on the degree of cell excitation and, in addition, is frequency-dependent. It has been demonstrated that the key target of these peptides are N-methyl-D-aspartate glutamate receptors. We propose that two peptide pools are involved in the initial and late phases of LTP. The possible significance of peptide cell regulation in mechanisms of neuronal plasticity is discussed.