Brain Research, 294 (1984) 127-132 127 Elsevier BRE 20045 Electrophysiology of pars compacta cells in the in vitro substantia nigra m a possible mechanism for dendritic release R. LLINAS, S. A. GREENFIELD* and H. JAHNSEN** Department of Physiology and Biophysics, New York University Medical Center, 550 FirstAvenue New York, NY 10016 (U.S.A.) (Accepted October 25th, 1983) Key words: substantia nigra - - dendritic release - - in vitro recording - - intracellular recording - - calcium currents - - dendritic spiking The electrophysiologicalproperties of neurons in the pars compacta of the substantia nigra have been examined in vitro in guinea pig mesencephalic slices. These cells display a set of voltage- and Ca2+-dependent ionic conductances which confer upon them rather unique electrophysiological characteristics. In particular, the results indicate the presence of two separate dendritic Ca -~+ conduc- tances. One is inactivated at rest membrane potential and is de-inactivated by membrane hyperpolarization. The second resembles that responsible for dendritic spikes in other neurons. These conductances fulfil most of the physiological and pharmacological re- quirements for the ionic mechanisms underlying Ca2+-dependent dendritic release. It is well established that dopamine (DA) is spon- taneously released from dendrites of nigro-striatal neurons: this release is enhanced by elevated concen- trations of K + and is Cae+-dependent 2. However, re- lease of DA from nigral dendrites is not reduced by blocking nerve impulse conduction with either TTX 2, or 7-butyrolactone 15. Acetylcholinesterase (ACHE) is also released (independently of cholinergic trans- mission) from non-terminal processes of DA-con- taining pars compacta neurons m. This release is again Ca2+-dependent 9 and resistant to TTX (Green- field and Chesselet, unpublished observations). The relationship between dendritic release and neuronal discharge is not clear. Dendritic DA release cannot be regarded simply as a direct index of the fir- ing frequency of nigro-striatal neurons, as serotonin and acetylcholine both enhance dendritic DA re- lease 7. Yet, iontophoretic studies show that the for- mer has a depressant effect on these cells 6 whereas the latter is excitatory 31. Substance P also increases pars compacta cell discharge 31 but unlike acetylcho- line, application of this peptide leads to a decrease in DA release7. Finally, when iontophoresed onto iden- tiffed nigro-striatal neurons, 7-aminobutyric acid (GABA) produces a rapid and marked inhibition of their firing29 while DA levels in nigral perfusates are unaffecte&. A similar problem arises in relating neu- ronal discharge to AChE release. Infusion of am- phetamine depresses the firing rate of nigro-striatal neurons 14, while increasing AChE release~l, We have approached the problem of the apparent inde- pendence of dendritic release from neuronal firing by examining the electrophysiological properties of ni- gral cells in vitro in guinea pig mesencephalic slices. The techniques utilized for these experiments are similar to those described in previous publications from this laboratory23. Following anesthesia guinea pigs were decapitated and the mesencephalon isola- ted and blocked. The tissue was kept at 6-10 °C and 400-#m slices made using an Oxford Vibratome. Re- cordings were made from cells in the pars compacta of substantia nigra under direct vision. Intracellular dye injections (Fig. 1) further confirmed their identi- ty: filled cells correlated well with the classical mor- phological description of the principal type of neuron (82-90%) found in this region JT. In addition, neurons * Present address: University Laboratory of Physiology, Parks Road, Oxford OX1 3PT U.K. ** Present address: Institute of Neurophysiology, Panum, Blegdamsvej 3C, 2200 Copenhagen N, Denmark. Correspondence: R. Llinfis, Department of Physiology and Biophysics, New York University Medical Center, 550 First Avenue, New York, NY 10016, U.S.A. 0006-8993/84/$03.00 © 1984 Elsevier Science Publishers B.V.