Responses of midbrain dopamine neurons to behavioral trigger stimuli in the monkey

Abstract

Destruction of the midbrain dopamine (DA) system in Parkinsonian man and experimental animals leads to deficits in initiation of behavior, motor performance, and cognitive mechanisms. We have investigated the extracellular impulse activity of single midbrain DA neurons in unlesioned monkeys performing in a controlled behavioral task that was designed to paradigmatically test behavioral reactivity. Animals were trained to execute natural forelimb reaching movements for food reward in response to a trigger stimulus. Presumptive DA neurons were histologically located in the pars compacta of substantia nigra and in neighboring areas A8 and A10. They spontaneously discharged polyphasic impulses of relatively long duration (1.4-3.6 ms) and at low frequencies (0.5-8.5/s). Systemic injections of low doses of the DA autoreceptor agonist apomorphine (0.05-0.2 mg/kg) depressed the activity of virtually all thus tested DA neurons. In following established criteria, these characteristics strongly suggest the DAergic nature of the recorded neurons. The majority of midbrain DA neurons (70 of 128) responded to the behavioral trigger stimulus of the task with a short burst of impulses. Latencies ranged from 39 to 105 ms (median 65 ms) for onset and from 65 to 165 ms (median 95 ms) for peak of responses. Responses occurred before arm movement and at the time of or before onset of electromyographic (EMG) activity in prime mover muscles. Responses were time-locked to the stimulus and not to the onset of movement or EMG. Responses remained present in most neurons but were reduced when vision of the behavioral trigger stimulus was prevented while maintaining the associated acoustic signals. In another variation of the task, most neurons also responded to a stimulus that was physically identical to the behavioral trigger but to which the animal made no movement. The activity of a few DA neurons (11 of 128) was reduced following presentation of the behavioral trigger stimulus, with latencies comparable to those of activations. The activity of many DA neurons was increased (40 of 128) or reduced (22 of 128) during execution of the forelimb reaching movement. These changes were of a slow and moderate nature, and were minor compared with responses to the behavioral trigger stimulus. About half of movement-related neurons also responded to the behavioral trigger. The activity of a few DA neurons was increased (11 to 128) or reduced (1 to 128) when the food reward reached the mouth. These changes did not occur with spontaneous mouth movements. About half of these neurons also responded to the behavioral trigger.(ABSTRACT TRUNCATED AT 400 WORDS)