Estimates of the axonal refractory period of midbrain dopamine neurons: their relevance to brain stimulation reward

Abstract

Psychophysical studies have shown that the directly activated neurons subserving the rewarding effect produced by electrical stimulation of the medial forebrain bundle (MFB) have refractory periods (RPs) shorter than those of dopaminergic (DA) neurons: this suggests that the directly stimulated substrate for the rewarding effect does not include DA neurons. Comparison of RP estimates. however, is difficult since those of DA neurons were obtained with the standard electrophysiological technique that characterizes cell body/initial segment rather than the directly stimulated axonal segment. Using electrophysiological recording techniques in urethane anesthetized rats, we re-estimated and compared the RP of DA neurons that project to the MFB and the ventral striatum (VST) with two stimulation procedures: one that characterizes the axonal segment near the stimulation electrode and the standard one that characterizes the cell body/initial segment near the recording electrode. Results showed that DA axonal RPs range from 1.0 to 2.2 ms, whereas cell body/initial segment RPs range from 1.0 to 3.0 ms. The axonal RP was equal to or shorter (mean difference = 0.22 ms, n = 15) than the cell body/initial segment RP. Axonal RP estimates for MFB sites range from 1.3 to 2.1 ms. values that slightly overlap with the late recovery from refractoriness reported in psychophysical studies for reward-relevant neurons. Axonal RP estimates obtained for VST sites were very similar (mean = 1.66, LH and 1.62 ms, VST) suggesting that the excitability of DA axons does not differ along their path. These results further support the hypothesis that DA axons are unlikely to constitute a major component of the directly-stimulated reward-relevant axons in the MFB. They also suggest that the direct contribution of DA axons to reward produced by VST stimulation is more important than by the MFB.