Substantia Nigra Pars Reticulata Activity Research Articles

Quantitative analysis of substantia nigra pars reticulata activity during a visually guided saccade task.

Several lines of evidence suggest that the pars reticulata subdivision of the substantia nigra (SNr) plays a role in the generation of saccadic eye movements. However, the responses of SNr neurons during saccades have not been examined with the same level of quantitative detail as the responses of neurons in other key saccadic areas. For this report, we examined the firing rates of 72 SNr neurons while awake-behaving primates correctly performed an average of 136 trials of a visually guided delayed saccade task. On each trial, the location of the visual target was chosen randomly from a grid spanning 40 degrees of horizontal and vertical visual angle. We measured the firing rates of each neuron during five intervals on every trial: a baseline interval, a fixation interval, a visual interval, a movement interval, and a reward interval. We found four distinct classes of SNr neurons. Two classes of neurons had firing rates that decreased during delayed saccade trials. The firing rates of discrete pausers decreased after the onset of a contralateral target and/or before the onset of a saccade that would align gaze with that target. The firing rates of universal pausers decreased after fixation on all trials and remained below baseline until the delivery of reinforcement. We also found two classes of SNr neurons with firing rates that increased during delayed saccade trials. The firing rates of bursters increased after the onset of a contralateral target and/or before the onset of a saccade aligning gaze with that target. The firing rates of pause-bursters increased after the onset of a contralateral target but decreased after the illumination of an ipsilateral target. Our quantification of the response profiles of SNr neurons yielded three novel findings. First, we found that some SNr neurons generate saccade-related increases in activity. Second, we found that, for nearly all SNr neurons, the relationship between firing rate and horizontal and vertical saccade amplitude could be well described by a planar surface within the range of movements we sampled. Finally we found that for most SNr neurons, saccade-related modulations in activity were highly variable on a trial-by-trial basis.

The anticonvulsant gabapentin decreases firing rates of substantia nigra pars reticulata neurons

Gabapentin is a novel anti-epileptic drug which enhances GABA (γ-aminobutyric acid) turnover in certain brain regions, including substantia nigra. However, the functional consequences of GABA turnover increases in response to gabapentin and their potential involvement in the anticonvulsant action of this drug are not known. In the present study, we examined the effects of gabapentin on the extracellular, single unit activity of nondopaminergic (presumably GABAergic) neurons of the substantia nigra pars reticulata in rats. During the recordings, the animals were infused with the narcotic opioid analgesic fentanyl, associated with a skeletal muscle relaxant and artificial ventilation. The spontaneous firing of substantia nigra pars reticulata neurons was determined up to about 2 h after i.v. or i.p. administration of gabapentin at doses of 15–30 mg/kg. After both routes of administration, gabapentin markedly reduced neuronal firing when administered at a dose of 20–30 mg/kg, while 15 mg/kg were ineffective in this regard. The suppressive effect of gabapentin was rapid in onset (2 min after i.v. and about 20 min after i.p. injection), reached peak values of about 70% below predrug baseline after about 45–60 min, and remained at this level for at least 2 h. Vehicle administration had no effect on substantia nigra pars reticulata neurons. The ability of gabapentin to alter substantia nigra pars reticulata firing does correlate with its known ability to increase nigral GABA turnover. Since a substantial body of evidence suggests that the substantia nigra pars reticulata is a critical site at which decrease of neuronal firing by potentiation of GABAergic influences results in protection against various seizure types, the suppressive effect of gabapentin on substantia nigra pars reticulata activity may contribute to the anticonvulsant action of this drug.

Effects of D 1 and D 2 dopamine receptor stimulation on the activity of substantia nigra pars reticulata neurons in 6-hydroxydopamine lesioned rats: D 1/D 2 coactivation induces potentiated responses

Extracellular single unit recording techniques were used to compare the effects of selective and non-selective dopamine agonists on substantia nigra pars reticulata activity in rats with 6-hydroxydopamine induced lesions of the nigrostriatal dopamine pathway. As previously shown, apomorphine (0.32 mg/kg), a dopamine agonist that interacts with both D 1 and D 2 dopamine receptor subtypes, produced consistent inhibitions of substantia nigra pars reticulata activity in these animals. The D 1-receptor agonist, SKF 38393 (RS-SKF 38393, 10 mg/kg), also induced significant inhibitions in the activity of these neurons in 6-hydroxydopamine lesioned rats, although less consistently than did apomorphine. The effects of SKF 38393 were reversed by the D 1-antagonist, SCH 23390. The D 2 selective agonist quinpirole was considerably less effective than apomorphine at inhibiting substantia nigra pars reticulata activity at doses up to 1 mg/kg. Since comparable experiments have shown that quinpirole is as effective as apomorphine at producing dopamine D 2-autoreceptor-mediated effects on dopamine neuron activity, quinpirole's lack of efficacy in the present study relative to that of apomorphine does not appear to be related to differences in relative potency for central D 2-receptors using this route of administration. Rather, the relative effectiveness of SKF 38393 on pars reticulata activity suggests that selective stimulation of D 1-receptors is at least, if not more, efficacious than selective stimulation of D 2-receptors at inducing alterations in the activity of substantia nigra pars reticulata neurons in 6-hydroxydopamine lesioned rats. The simultaneous stimulation of both receptors, however, was considerably more effective than selective stimulation of either receptor subtype: doses of SKF 38393 and quinpirole which had no significant effect on nigral activity when administered alone brought about marked inhibition of the firing of these cells when administered simultaneously. No such inhibition was seen when the inactive enantiomer, S-SKF 38393, was substituted for the racemic form of SKF 38393 in this protocol. These observations in 6-hydroxydopamine lesioned rats support other recent findings indicating that the two dopamine receptor sub-types can interact in a synergistic way to affect basal ganglia output.

Changes in substantia nigra pars reticulata activity following lesions of the substantia nigra pars compacta

Single unit activity of substantia nigra reticulata (SNr) neurons was recorded in normal rats and bilaterally in rats subjected to a unilateral 6-hydroxydopamine lesion of the substantia nigra compacta 2–4 weeks previously. Lesions were assessed by rotational behaviour to apomorphine. In normal rats the majority of neurons (63%) showed a regular firing pattern. Following lesion the percentage of these cells was similar in the SNr contralateral to the lesion but decreased on the lesioned side to 26%, whereas bursting activity developed (37% vs 5% in normal rats). The mean firing rate of reticulata neurons was slightly increased after lesion, but not statistically significant.

Visual and oculomotor functions of monkey substantia nigra pars reticulata. II. Visual responses related to fixation of gaze.

Visual and oculomotor functions of monkey substantia nigra pars reticulata. II. Visual responses related to fixation of gaze.

Visual and oculomotor functions of monkey substantia nigra pars reticulata. III. Memory-contingent visual and saccade responses.

Visual and oculomotor functions of monkey substantia nigra pars reticulata. III. Memory-contingent visual and saccade responses.

Spatial localization of saccade targets. I. Compensation for stimulation-induced perturbations in eye position.

1. Monkeys were trained to look to brief visual targets presented in a completely darkened room. On some trials, after the visual target disappeared but before a saccade to the target could be initiated, the eyes were driven to another position in the orbit by electrical stimulation of the superior colliculus. Retinocentric models of the saccadic system predict that a saccade with a predetermined distance and direction based entirely on retinal error will occur. If this were the case, gaze would miss the target location by a distance and direction equal to the vector of the stimulation-induced movement. Spatial models assume that the retinal error signal will be combined with information about the change in eye position produced by stimulation and predict that the animal will look to the position of the target in space. 2. Results confirm the predictions of spatial models. Animals compensated for the stimulation-induced perturbation by looking to the position of the target in space. The result predicted by retinocentric models-a saccade with a direction and amplitude based on retinal error alone-was never observed. 3. The eye movement that compensated for the change in eye position produced by stimulation was a saccade, not a passive, lowvelocity movement to an orbital position of mechanical equilibrium established by a tonic pattern of motoneuron activation specified by the visual target. This indicates that a new saccade command, based on stored information about the location of the retinal image and information about the new position of the eyes, had been issued. Computation of the vector of the compensatory saccade does not necessarily increase the latency of target acquisition. The interval between the end of a stimulation-induced saccade and the beginning of the compensatory saccade was frequently 20 ms or less, permitting the animal to acquire the target with a normal latency.