NEUROTROPHIC FACTOR MESSENGER-RNA EXPRESSION IN DENTATE GYRUS IS INCREASED FOLLOWING IN-VIVO STIMULATION OF THE ANGULAR BUNDLE

Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are two structurally-related neurotrophins synthesized in dentate gyr us granule cells and pyramidal neurons of the hippocampal formation. T hese neurons receive excitatory glutamatergic afferents from the entor hinal cortex via the angular bundle/perforant path. In the present stu dy, we tested whether electrophysiological stimulation of this glutama tergic pathway modifies NGF or BDNF messenger RNA (mRNA) expression in vivo. Within hours following brief trains of high frequency angular b undle stimulation, the levels of mRNA encoding both neurotrophins were increased exclusively in granule cells of the ipsilateral dentate gyr us. The increase in neurotrophic factor mRNA expression was found to b e mediated through the N-methyl-D-aspartate (NMDA) glutamate receptor subtype, and occurred in the absence of seizure. These findings provid e evidence that neurotrophic factor mRNA levels in the hippocampal for mation are increased by direct activation of excitatory afferents orig inating in the entorhinal cortex. We suggest that the function of some neurotrophin-responsive neuronal populations may depend upon the inte grity and activity of neurons in the entorhinal cortex, a population o f neurons reported to be compromised in patients with Alzheimer's dise ase.