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 whether nerve growth factor and neurotrophin-3 are capable of altering the excitability of neurons of the mesencencephalic trigeminal nucleus. In contrast 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 oscillatory activity that is observed in these cells and a significant decrease in their threshold current. The latency of these effects ranged from 2 to 80 s and the duration ranged from 2 to 11 min. Neurotrophin-3 induced a decrease in input resistance and resting membrane potential in 58% of the cells; nerve growth factor induced a decrease in input resistance and resting membrane potential in 35% of the neurons. The spike configuration and action potential afterhyperpolarization potential remained unchanged following neurotrophin application. Tetrodotoxin blocked the membrane potential oscillatory activity of trigeminal mesencephalic neurons. Neurotrophin-induced effects were not blocked by the tyrosine kinase inhibitor K-252a, whereas IgG-192, an antibody directed to the neurotrophin low-affinity receptor, enhanced excitability, as did neurotrophins. These results demonstrate that neurotrophins are capable of producing a rapid increase in the excitability of trigeminal mesencephalic neurons and suggest that their effects may be mediated by low-affinity neurotrophin receptors.