BRAIN-DERIVED NEUROTROPHIC FACTOR INCREASES THE ELECTRICAL-ACTIVITY OF PARS COMPACTA DOPAMINE NEURONS IN-VIVO

Chronic infusions of brain-derived neurotrophic factor (BDNF) immediat ely above the substantia nigra augment spontaneous locomotion, rotatio nal behavior, and striatal dopamine (DA) turnover, indicating that BDN F increases functions of the nigrostriatal DA system. Because the func tion of the nigrostriatal DA system is related to the electrical activ ity of DG neurons, we investigated the effect of BDNF on the electrica l activity of DA neurons in the substantia nigra pars compacta in vivo . Chronic supranigral infusions of BDNF (12 mu g/day), nerve growth fa ctor (11 mu g/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 fi ring rate by 32%, and increased the number of action potentials contai ned within bursts. Neither nerve growth factor nor phosphate-buffered saline infusions altered any of these properties relative to unoperate d animals. In addition, extremely fast-firing DA neurons (>10 spikes p er sec) were commonly found only in the BDNF-infused animals. These re sults demonstrate neurotrophin effects on the electrical activity of i ntact central nervous system neurons in vivo and suggest that the incr eases in locomotor behavior and striatal dopamine turnover obtained du ring supranigral BDNF infusions may result from increases in the elect rical activity of DA neurons.