Behavior-related changes in the activity of substantia nigra pars reticulata neurons in freely moving rats

Abstract

As one of the primary targets of the striatum, the substantia nigra pars reticulata (SNr) has been hypothesized to play a role in normal motor behavior. Specifically, inhibition of usually high, tonic SNr output is predicted to correlate with motor activation. While support for this has come primarily from electrophysiological studies in primates performing goal-directed movements, we tested this hypothesis in rats behaving in an open-field arena. SNr single-unit activity was recorded during spontaneous bouts of open-field behavior (e.g., head and body movements, locomotion) and after rats were given d-amphetamine (1.0 mg/kg, s.c.), which reliably increases motor activity and elevates the firing of motor-related striatal neurons. Prior to drug administration, SNr neurons had either regular, slightly irregular or irregular firing patterns when animals rested quietly. During movement, some inhibitions were observed, but the majority (∼79%) of analyzed units increased firing by as much as 38%. Regardless of the predrug behavioral response of the cell, amphetamine strongly inhibited firing rate (∼90% below nonmovement baseline) and changed firing pattern such that all cells fired irregularly. Subsequent injection with the dopamine antagonist haloperidol (1.0 mg/kg, s.c.) reversed amphetamine-induced inhibitions in all tested cells, which supports a role for dopamine in this effect. These results suggest that the pattern of striatal activity established by amphetamine, which may be critical for determining the drug-induced behavioral pattern, is represented in the SNr regardless of the predrug behavioral response of the cell.

Introduction

Ample evidence, primarily from electrophysiological recording in awake, behaving primates and rats, has implicated the basal ganglia in the control of movement. For example, striatal neurons, which have low or silent levels of activity during periods of quiet rest 4, 17, 46, mostly increase discharge rate during movement 2, 4, 14, 19, 67. Rats tested in an open-field arena show increases in striatal activity in close temporal association with spontaneous head or neck movements or in relation to gross body movements (e.g., locomotion and rearing) 31, 33, 55. Striatal neurons also have been reported to alter firing rate in association with sensory-triggered movements 11, 20, 66. Many of these responses, moreover, depend on the behavioral context in which they occur (e.g., a change in firing rate to a sensory-triggered movement may not occur when the movement occurs outside the task). Interestingly, the proportion of striatal neurons having both sensory- and motor-related components appears to be higher in rats than in primates, suggesting a greater convergence of sensory and motor signals in rat striatum 3, 20, 26. It appears, therefore, that striatal neurons serve an important integrative role in motor behavior.

Perhaps the most important striatal target in rats is the substantia nigra pars reticulata (SNr), which receives both direct and indirect projections from striatum and then routes this information to thalamic as well as descending nuclei [34]. Activation of the direct, striatonigral pathway predominantly inhibits SNr neurons via release of GABA 15, 69, while activation of the indirect, striatopallidal pathway would be expected to have the opposite effect 1, 62. The main striatal control of the SNr appears to be via the striatonigral pathway, as most SNr units are inhibited by striatal stimulation 15, 29except during iontophoresis of the GABA antagonist bicuculline [65].

The SNr is dominated by GABA-containing projection cells interspersed with clusters of dopamine neurons 6, 18, 24and perhaps a small number of GABA- or peptide-containing interneurons 22, 28, 39. Although GABA and, to a lesser extent dopamine and glutamate, appear to play a critical role in regulating the activity of SNr neurons, their electrophysiological features clearly distinguish them from dopamine neurons 23, 29, 30. SNr projection units, for example, are characterized by short biphasic spikes, high levels of spontaneous activity, and a sensitivity to depolarizing currents that permits repetitive firing up to 200 spikes/s.

Relatively little information is available on SNr function during behavior. A classic view, largely based on data from monkeys performing visual fixation tasks [35]and further supported by experiments in anesthetized rats 13, 16, predicts a high level of SNr basal activity that declines during movement. The implication is that tonically active inhibitory SNr outputs normally keep “downstream” movement generators in check to suppress inappropriate or unwanted behavior 12, 48. Movement would be expected to correlate with a reduction in this tonic rate. To test this hypothesis directly, we recorded SNr single-unit activity in rats engaged in open-field behaviors that occurred either spontaneously or in response to probing by the experimenter. Some animals also received 1.0 mg/kg d-amphetamine (AMPH), which increases motor activation.