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Reductions in SNAP-25 immunohistochemistry were found after removing the glutamatergic and cholinergic inputs to the rat hippocampus. SNAP-25 levels were normalised by 1 month after afferent lesions. Surprisingly, a superimposed cholinergic lesions did not affect the return to normal SNAP-25 levels after a long-term entorhinal cortex lesion. It is concluded that changes in SNAP-25 may represent early markers of synaptic loss following afferent lesions to the hippocampus.