Brain-derived neurotrophic factor increases the electrical activity of pars compacta dopamine neurons in vivo

Chronic infusions of brain-derived neurotrophic factor (BDNF) immediately above the substantia nigra augment spontaneous locomotion, rotational behavior, and striatal dopamine (DA) turnover, indicating that BDNF increases functions of the nigrostriatal DA system. Because the function of the nigrostriatal DA system is related to the electrical activity of DA neurons, we investigated the effect of BDNF on the electrical activity of DA neurons in the substantia nigra pars compacta in vivo. Chronic supranigral infusions of BDNF (12 micrograms/day), nerve growth factor (11 micrograms/day), or phosphate-buffered saline were started 2 weeks before the electrophysiological recordings. BDNF increased the number of spontaneously active DA neurons by 65-98%, increased the average firing rage by 32%, and increased the number of action potentials contained within bursts. Neither nerve growth factor nor phosphate-buffered saline infusions altered any of these properties relative to unoperated animals. In addition, extremely fast-firing DA neurons (> 10 spikes per sec) were commonly found only in the BDNF-infused animals. These results demonstrate neurotrophin effects on the electrical activity of intact central nervous system neurons in vivo and suggest that the increases in locomotor behavior and striatal dopamine turnover obtained during supranigral BDNF infusions may result from increases in the electrical activity of DA neurons.