Brain-derived neurotrophic factor enhances fast excitatory synaptic transmission in human epileptic dentate gyrus

Brain-derived neurotrophic factor (BDNF) has trophic effects and modulates synaptic transmission in the hippocampal formation in animal studies. It is also upregulated in acute and chronic epilepsy models and in human tempora l lobe epilepsy. This study was undertaken to examine the effects of BDNF o n fast synaptic transmission in the human epileptic dentate gyrus. Hippocam pal specimens were acquired from patients with temporal lobe epilepsy durin g surgical removal of the anterior temporal lobe intended to treat the epil eptic condition. Whole-cell patch-clamp recordings were obtained from denta te granule cells in transverse hippocampal slices in vitro. Application of BDNF increased the amplitude and frequency of spontaneous excitatory postsy naptic currents and increased the amplitude of evoked excitatory postsynapt ic currents. BDNF had no effect on spontaneous inhibitory postsynaptic curr ents but produced a decrease in amplitude of evoked inhibitory postsynaptic currents. BDNF's effects were abolished by coapplication of the tyrosine k inase inhibitor K252a. Therefore, BDNF enhances fast excitatory transmissio n in the epileptic human dentate gyrus and may play an important role in ep ileptogenesis in temporal lobe epilepsy. This raises the possibility of des igning therapies for this disorder that may be both anticonvulsant and anti epileptogenic.