Asymmetric relationships between homosynaptic long-term potentiation and heterosynaptic long-term depression

Abstract

All synaptically-based neuropsychological theories of learning postulate that there are changes resulting from neural activity which are long-lasting and confined to specific sets of synapses^1–3. In the past decade a form of synaptic strengthening known as long-term potentiation (LTP) has been found which results from high-frequency neural activity and is of sufficient duration to model as a learning mechanism^4,5. Some early tests of the synaptic specificity of LTP in area CA1 of the hippocampus indicated that although LTP was specific to the tetanized pathway, in a converging untetanized pathway it was associated with depression of synaptic transmission lasting for at least 30 min^6–8. However, others have found that this heterosynaptic depression more usually decays within 5–15 min post-tetanus despite the maintenance of LTP in the tetanized pathway^9–13. Similarly, in the dentate gyrus (DG), LTP of either the lateral (LPP) or medial (MPP) components of the perforant path afferents has been associated with only short-lasting reciprocal heterosynaptic depression¹⁴. Here, using more detailed measurement of stimulus intensity curves, we report that tetanization of either MPP or LPP reliably depresses synaptic transmission in the other pathway for at least 3 h. This heterosynaptic depression, considerably smaller than the usual magnitude of LTP, was obtained regardless of whether LTP had been produced in the tetanized homosynaptic pathway. Heterosynaptic long-term depression was not observed if the test pathway had been previously tetanized.