Responses of nigrostriatal dopamine neurons to high-intensity somatosensory stimulation in the anesthetized monkey

Abstract

Nigrostriatal dopamine (DA) neurons of the mammalian midbrain play an important role in behavioral reactions. Their destruction in Parkinsonian patients and experimentally lesioned animals leads to a reduction and slowing of movements as well as other motor, cognitive, and motivational deficits. We tested the responses of DA neurons to somatosensory stimulation to gain insight into the nature of peripheral information reaching these neurons. Experiments were performed as repeated sessions in two anesthetized monkeys having chronically implanted recording chambers, thereby reducing the number of primates required for experimentation. Midbrain DA neurons were characterized by their histological location, by the form, duration, and frequency of extracellularly recorded, spontaneously occurring impulses, by antidromic activation from caudate and putamen, and by the reduction of impulse rate following systemic administration of low doses of the DA autoreceptor agonist apomorphine. Half of the midbrain DA neurons (65 of 145 neurons, 45%) were antidromically activated from chronically implanted stimulating electrodes in caudate (35 neurons), putamen (47 neurons), or both structures (17 of them). Conduction velocities ranged from 0.7 to 2.5 m/s, with medians of 1.2 and 1.5 m/s for neurons projecting to caudate and putamen, respectively. Half of the midbrain DA neurons were depressed (72 of 140 neurons, 51%) and less than a quarter activated (24 of 140 neurons, 17%) by intense noxious pinch stimulation to the body surface. Innocuous, even intense, surface or deep somatosensory stimuli were ineffective. Pinch responses continued during the whole stimulating period of several seconds in most DA neurons. There was no response habituation during repeated stimulation. Convergence between spinal and trigeminal input and from both body sides was seen for virtually all noxious pinch responses. Thus DA neurons typically responded in the same direction to pinch stimulation of hand, foot, face, tail, and dorsum of both sides. Systemic administration of the DA receptor antagonist haloperidol (0.33 or 0.50 mg/kg) strongly reduced pinch responses in all seven DA neurons tested. This provides evidence for an involvement of DAergic neurotransmission in the representation of exteroceptive input in the brain. The results show that midbrain DA neurons projecting to the striatum respond to noxious somatosensory input in the anesthetized monkey. The bilateral nontopographic nature of the responses does not support a role in precise stimulus recognition, rather it suggests a mechanism involved in basic neuronal processes underlying behavioral responsiveness.