ENTORHINAL CORTEX REGULATION OF MULTIPLE BRAIN-DERIVED NEUROTROPHIC FACTOR PROMOTERS IN THE RAT HIPPOCAMPUS

Developmental or degenerative damage of the neuronal architecture in t he entorhinal cortex may disintegrate a functional part of hippocampal input since the entorhinal cortex provides a major source of neocorti cal and subcortial input to the hippocampus these alterations, such as seen in Alzheimer's disease,(15) schizophrenia(5) and temporal lobe e pilepsy(29) are likely to be associated with cognitive deficits. To un derstand and the basis for pathological changes in the corticohippocam pal loop it is important to study mechanisms involved in neuronal plas ticity. Brain-derived neurotrophic factor provides a possible substrat e to mediate such plasticity. We have previously provided evidence tha t stimulation of hippocampal afferents transynaptically increase the l evel of brain-derived neurotrophic factor messenger RNA within the hip pocampus.(21) In the present study we have investigated whether differ ent brain-derived neurotrophic factor messenger RNAs are specifically regulated in the hippocmapus. We provide evidence for a differential a nd dose-dependent regulation of the different brain-derived neurotroph ic factor promoters in the hippocampus by afferents in the entorhinal cortex. Our finding of a graded regulation is in contrast to earlier e vidence of an ''all-or-none'' type of regulation.(3)