Dopamine controls the firing pattern of dopamine neurons via a network feedback mechanism

^*Vollum Institute, Oregon Health and Science University, Portland, OR 97201; and ^†Howard Hughes Medical Institute, Department of Biochemistry and the Neurobiology and Behavior Program, University of Washington, Seattle, WA 98195-7370

Contributed by Richard D. Palmiter

Abstract

Changes in the firing pattern of midbrain dopamine neurons are thought to encode information for certain types of reward-related learning. In particular, the burst pattern of firing is predicted to result in more efficient dopamine release at target loci, which could underlie changes in synaptic plasticity. In this study, the effects of dopamine on the firing patterns of dopaminergic neurons in vivo and their electrophysiological characteristics in vitro were examined by using a genetic dopamine-deficient (DD) mouse model. Extracellular recordings in vivo showed that, although the firing pattern of dopamine neurons in normal mice included bursting activity, DD mice recordings showed only a single-spike pattern of activity with no bursts. Bursting was restored in DD mice after systemic administration of the dopamine precursor, l-3,4-dihydroxyphenylalanine (l-dopa). Whole-cell recordings in vitro demonstrated that the basic electrophysiology and pharmacology of dopamine neurons were identical between DD and control mice, except that amphetamine did not elicit a hyperpolarizing current in slices from DD mice. These data suggest that endogenously released dopamine plays a critical role in the afferent control of dopamine neuron bursting activity and that this control is exerted via a network feedback mechanism.

Footnotes

↵ ‡ To whom correspondence should be addressed. E-mail: palmiter{at}u.washington.edu.
Abbreviations:

CV,

coefficient of variation;

l-dopa,

l-3,4-dihydroxyphenylalanine;

DD,

dopamine-deficient;

GABAB,

γ-aminobutyric acid type B;

mGluR,

metabotropic glutamate receptor