Intracellular and extracellular electrophysiology of nigral dopaminergic neurons--1. Identification and characterization

Abstract

Intracellular recordings were obtained from directly identified rat nigral dopamine cells in vivo. This identification was based on an increase in glyoxylic acid-induced catecholamine fluorescence in the impaled dopamine neurons. One of three compounds was injected intracellularly into each cell to produce the heightened fluorescence: (1) L-DOPA, to increase the intracellular dopamine content by precursor loading; (2) tetrahydrobiopterin, a cofactor for tyrosine hydroxylase, to increase intracellular dopamine concentration through activation of the rate-limiting enzyme for dopamine synthesis and (3) colchicine, to arrest intraneuronal transport and thus allow the build-up of dopamine synthesizing enzymes and dopamine in the soma. In addition, dopamine cells were antidromically activated from the caudate nucleus and collision with a directly elicited action potential was demonstrated. Identified dopamine neurons were shown to possess an input resistance of 31.2 +/- 7.4 M omega (means +/- SD) and a time constant of 12.1 +/- 3.2 ms. The action potentials were of long duration (2.75 +/- 0.5 ms) with a marked break between the initial segment and the somatodendritic spike components. The initial segment was the only component commonly elicited during antidromic activation. Spontaneously occurring action potentials were usually preceded by a slow, pacemaker-like depolarization. Burst firing by summation of depolarizing afterpotentials was observed to occur spontaneously, but could not be triggered by short depolarizing current pulses. Intravenously administered apomorphine demonstrated the same inhibitory effect on cell firing that was previously reported to occur when recording extracellularly from identified dopaminergic neurons. The determination of the electrophysiological characteristics of a population of cells directly identified as containing a specific neurotransmitter (in this case, dopamine) may allow one to construct better models of a system's functioning. Thus, the high input resistance and long time constant of dopamine-containing cells, combined with their burst/pause firing mode, may be important functionally with respect to a possible modulatory effect of dopamine in postsynaptic target areas.