Neurotrophin-evoked rapid excitation through TrkB receptors

Neurotrophins are a family of structurally related proteins that regulate t he survival, differentiation and maintenance of function of different popul ations of peripheral and central neurons(1-3). They are also essential for modulating activity-dependent neuronal plasticity(4-7). Here we show that n eurotrophins elicit action potentials in central neurons. Even at low conce ntrations, brain-derived neurotrophic factor (BDNF) excited neurons in the hippocampus, cortex and cerebellum. We found that BDNF and neurotrophin-4/5 depolarized neurons just as rapidly as the neurotransmitter glutamate, eve n at a more than thousand-fold lower concentration. Neurotrophin-3 produced much smaller responses, and nerve growth factor was ineffective. The neuro trophin-induced depolarization resulted from the activation of a sodium ion conductance which was reversibly blocked by K-252a, a protein kinase block er which prefers tyrosine kinase Trk receptors(8). Our results demonstrate a very rapid excitatory action of neurotrophins, placing them among the mos t potent endogenous neuro-excitants in the mammalian central nervous system described so far.