Neurotrophin-induced rapid enhancement of membrane potential oscillations in mesencephalic trigeminal neurons

We have proposed that neurotrophins, in addition to their trophic actions, act as neuromodulators in the adult central nervous system. As a first step to test this hypothesis, we examined in the adult rat slice preparation wh ether nerve growth factor and neurotrophin-3 are capable of altering the ex citability of neurons of the mesencencephalic trigeminal nucleus. In contra st to vehicle pressure microapplication, which did not evoke changes in the electrophysiological properties of these neurons, neurotrophin application produced a significant increase in amplitude of the membrane potential osc illatory activity that is observed in these cells and a significant decreas e in their threshold current. The latency of these effects ranged from 2 to 80 s and the duration ranged from 2 to 11 min. Neuotrophin-3 induced a dec rease in input resistance and resting membrane potential in 58% of the cell s; nerve,growth factor induced a decrease in input resistance and resting m embrane potential in 35% of the neurons. The spike configuration and action potential afterhyperpolarization potential remained unchanged following ne urotrophin application. Tetrodotoxin blocked the membrane potential oscilla tory activity of trigeminal mesencephalic neurons, Neurotrophin-induced eff ects were not blocked by the tyrosine kinase inhibitor K-252a, whereas IgG- 192, an antibody directed to the neurotrophin low-affinity receptor, enhanc ed excitability, as did neurotrophins. These results demonstrate that neurotrophins are capable of producing a rap id increase in the excitability of trigeminal mesencephalic neurons and sug gest that their effects may be mediated by low-affinity neurotrophin recept ors. (C) 1999 IBRO. Published by Elsevier Science Ltd.