Activity in monkey substantia nigra neurons related to a simple learned movement

Summary Single cell activity was recorded in the pars compacta (SNc) and pars reticulata (SNr) of the substantia nigra (SN) in 4 unanesthetizedMacaca fascicularis to determine the motor role of the nucleus. Animals were trained to perform a simple task that involved moving a lever by elbow flexion-extensions, in the horizontal plane using the hand contralateral to the recording site. Two monkeys learnt to execute the task on both sides. Electromyograms (EMG) of limb muscles were recorded simultaneously with SN neurons. Discharge rate modulation related to specific movement phases was present in 35% of the neurons. A significant positive correlation of the discharge rate with movement velocity and amplitude was found in SNc and SNr neurons. Some SNr cells discharged in anticipation of the EMG, suggesting a participation of the nucleus in the preparation of movement. The activity of SNr neurons was also related to movement of the left and right upper limb. In conclusion, the SN seems to play an important role in the control of specific motor mechanisms, probably modulating movement velocity, amplitude and direction, with little participation of somatosensory feedback. The involvement of the SNr in the coordination of bilateral arm activity is discussed.     

Regional heterogeneity of dopaminergic deficits in vervet monkey striatum and substantia nigra after methamphetamine exposure

Methamphetamine (METH)-induced neurotoxicity within the striatum and substantia nigra of the vervet monkey was characterized by heterogeneous decreases in immunoreactivity (IR) for dopamine system phenotypic markers. Decreases in IR for tyrosine hydroxylase (TH), dopamine transporter (DAT), and the vesicular monoamine transporter (VMAT2) were observed 1 week after METH HCI (2x2 mg/kg; 24 h apart). Regional changes throughout the rostrocaudal extent of the striatum were characterized by a gradient of neurotoxic effect (lateral greater than medial) and the preservation of patches of IR. The decreases in IR in the caudate and putamen were greater than those in the nucleus accumbens. The reduced IR in the METH-exposed striatum allowed for the visualization of dopamine phenotype cell bodies. Within the ventral midbrain, the METH-exposed substantia nigra pars compacta (SNc) also showed a heterogeneous loss of IR (lateral greater than medial). In contrast, the ventral tegmental area (VTA) showed only minor decreases in IR. The magnitude of the decreases in the SNc and VTA subregions corresponded to those observed in their respective striatal projection areas, suggesting that nigrostriatal neuron subpopulations were differentially reactive to METH. The profile of these drug-induced nigrostriatal dopamine system deficits resembles aspects of Parkinson's disease pathology and, as such, may provide a useful model with which to evaluate neuroprotective and neurorestorative strategies.     

Neurotensin increases tyrosine hydroxylase messenger RNA-positive neurons in substantia nigra after retrograde axonal transport.

In previous studies we have shown that labelled neurotensin injected into the rat striatum was found to be transported retrogradely in dopaminergic neurons through a process which was receptor and microtubule dependent. Now, we show, by in situ hybridization, the consequences of the striatal injection of neurotensin on the gene expression of tyrosine hydroxylase in the substantia nigra. Rats were injected with neurotensin or its fragments in the striatum of one side and with saline or the inactive fragment on the other. The number of nigral cells expressing tyrosine hydroxylase mRNA was found to increase by 40% after injection of neurotensin or its active fragment (neurotensin 8-13). In the same experimental conditions, the inactive fragment (neurotensin 1-8) was without effect. Time-course experiments revealed that the tyrosine hydroxylase mRNA was increased 4 h after neurotensin injection but not at 1 or 16 h. The fact that the increase of mRNA parallels the appearance of labelled neurotensin in the substantia nigra indicates that the changes in the gene expression of tyrosine hydroxylase might be the consequence of the retrograde axonal transport of neurotensin. These results represent the first evidence for the existence of a long-distance retrograde signalling process in which the neuropeptide and presumably its receptor may serve as information molecule between synapses and the cell body.     

Functional coupling between substantia nigra and basal ganglia homologues in amphibians

Neuroanatomical and pharmacological experiments support the existence of a homologue of the mammalian substantia nigra-basal ganglia circuit in the amphibian brain. Demarcation of borders between the striatum and pallidum in frogs, however, has been contentious, and direct evidence of functional coupling between the putative nigral and striatal homologues is lacking. To clarify basal ganglia function in anurans, the authors used expression of immediate-early gene egr-1 as a marker of neural activation in the basal ganglia of túngara frogs (Physalaemus pustulosus). Regional variation in egr-1 mRNA levels distinguished striatal and pallidal portions of the basal ganglia and supported the grouping of the striatopallidal transition zone with the dorsal pallidum. As further evidence for a functional coupling between the dopaminergic cells in the posterior tuberculum (the putative substantia nigra homologue) and the basal ganglia, a positive relationship was demonstrated between the size of the dopaminergic cell population and the neural activation levels within the dorsal pallidum.     

Role of the monkey substantia nigra pars reticulata in orienting behaviour and visually triggered arm movements

The role of the substantia nigra pars reticulata (SNpr) has been studied in the head-free monkey during orienting behaviour in response to visual instruction signals triggering head positioning and conditioned arm movement. During the behavioural responses we recorded the electromyographic activities of neck muscles and triceps brachii, head movement, horizontal electrooculogram and single unit activity of SNpr neurons. Activity of 38 neurons located in the medial part of SNpr were analysed during the visuo-motor task. Forty percent of these units showed a moderate decrease in tonic firing rate during postural preparation preceding the orientation toward eccentric visual signal. This decrease, unrelated with saccadic eye movements per se, was followed by a marked pause observed when the rewarded stimulus was switched on and the conditioned arm movement was executed to get the reward. These data suggest that the pause in discharge of these SNpr neurons are time locked with behaviourally relevant visual stimuli and/or appropriate motor responses.     

The activity of pars compacta neurons of the monkey substantia nigra in relation to motor activation

Experimental Brain Research - The extracellular activity of single pars compacta neurons of the substantia nigra was recorded in awake monkeys. Animals were subjected to a behavioral paradigm...     

Topographic distribution of the axonal endings from the sensorimotor and associative striatum in the macaque pallidum and substantia nigra

The striatopallidonigral connection was studied by injecting anterograde tracers into either the associative or the sensorimotor striatum in ten macaques. The results were analyzed using a precise cartographic method. Injections into various parts of the associative striatum (caudate nucleus and ventromedial putamen) produced a labeling of axons in the dorsomedial and ventral pallidal regions. These associative regions occupied two-thirds of the lateral pallidum and one-third of the medial pallidum. Bands of labeled axons from the sensorimotor striatum (dorsolateral putamen) were found in the remaining, central part of the two pallidal nuclei. In the substantia nigra, the rostral associative striatum projected medially to the pars reticulata, while the caudal parts projected laterally. The whole pars reticulata and lateralis thus appeared to receive associative striatal inputs. The sensorimotor striatal territory projected to the central part of the pars reticulata/lateralis. It was concluded that the two functional territories remain separate in the two pallidal nuclei but overlap in the middle third of the substantia nigra. However, due to their great size, the pallidal neurons located at the border of the two territories may receive striatal inputs from both the associative and the sensorimotor components in the same way that nigral neurons do.     

The activity of pars compacta neurons of the monkey substantia nigra is depressed by apomorphine

In the substantia nigra of anesthetized and awake monkeys, presumptive dopamine cells of the pars compacta were electrophysiologically discriminated against non-dopaminergic cells of the pars reticulata by their lower discharge rate (0.5–8 vs 20–130 imp./s), their longer impulse duration (means 2.05 vs 0.92 ms), and their exclusive depression following systemic injection of the dopamine agonist apomorphine (24 out of 30 compacta neurons at 0.05–0.1 mg/kg s.c.).     

Electrophysiological evidence for the dendritic localization of a calcium conductance in guinea-pig substantia nigra neurones in vitro

Summary Within the substantia nigra, anatomical, neurochemical and pharmacological findings strongly suggest that transmitter and protein are secreted from the dendrites of nigrostriatal neurones. This phenomenon may underlie a non classical modulatory cellular mechanism. Two conductances are generated in nigrostriatal neurones independent of somatic action potentials, that might mediate this modulation. However, these conductances have never been directly nor precisely located specifically within the dendrites. The aim of this study was to record the membrane properties of substantia nigra zona compacta neurones in response to selective sectioning of the population of long apical dendrites i.e. the removal of the zona reticulata. Intracellular recordings from substantia nigra zona compacta neurones were made from mesencephalic slices of the guinea-pig brain maintained in vitro. In cells without the apical dendrites, the membrane potential, input resistance and mean firing frequency was not significantly different from the control neurones. However, removal of the substantia nigra zona reticulata virtually abolished one conductance in particular. This conductance, seen in control neurones, is a long lasting slow depolarization which is resistant to tetrodotoxin blockade of sodium channels: rather, it is mediated by the entry of calcium ions and is optimally deinactivated at a hyperpolarised membrane potential. Hence, this study strongly suggests that this conductance is generated exclusively in the apical dendrites. It has been postulated that this long lasting calcium conductance is central to the modulation of nigrostriatal neuronal excitability. Thus, the apical dendrites could play a specific and active role in the functioning of nigrostriatal neurones.     

GABA receptors distribution in rat substantia nigra

The perikarya of the dopaminergic and non-dopaminergic neurons contained in the substantia nigra were selectively destroyed by a proper, local injection of 6-hydroxydopamine or kainic acid, respectively. Both lesions resulted in a marked decrease of the nigral GABA-binding sites. The effect of 6-hydroxydopamine was restricted to the high affinity receptors, while kainic acid specifically decreased the low affinity ones.     

Unilateral substantia nigra lesions and schedule-induced polydipsia

The present experiment investigated the effects of unilateral 6-hydroxydopamine lesions of the substantia nigra (SN) on schedule-induced polydipsia (SIP). Lesions were made in either the "dominant" or "non-dominant" hemisphere as defined by an amphetamine rotation test. It was found that unilateral lesions of either the "dominant" or "non-dominant" SN significantly reduced SIP and also significantly impaired somatosensory responsiveness as indicated by the "tactile extinction test." Somatosensory neglect was significantly greater following a lesion in the "dominant" hemisphere than "non-dominant" hemisphere.     

GABA-immunoreactive neurons in the mediodorsal nucleus of the monkey thalamus

The mediodorsal nucleus of the thalamus is an important component of the brain's circuitry for memory 9,20 and yet surprisingly little is known of its intrinsic organization. In the present study we have examined the distribution, spatial relationships and morphology of gamma-aminobutyric acid (GABA)-containing cells within the magnocellular and parvocellular subdivisions of the mediodorsal nucleus. These subdivisions have anatomically and functionally distinct connections with the orbital (limbic) and dorsolateral (association) areas of the prefrontal cortex, and accordingly, we investigated whether there were corresponding differences in their local circuit organization. Our findings show that round or ovoid GABA-immunoreactive neurons were abundant in both subdivisions. However, these neurons were larger in diameter in the magnocellular aspect (mean diameter = 10.4 +/- 0.1 micron) than in the parvocellular moiety (mean diameter = 9.9 +/- 0.1 micron) and the intensity of reactivity was also greater for the magnocellular neurons. Comparison of the densities of GABA-immunoreactive neurons revealed not only a greater density of neurons in the parvocellular division but also that the proportion of all neurons which were GABA-containing was greater in this region. These differences in the morphology and density of inhibitory local circuit neurons may contribute to the functional duality of prefrontal cortex innervated by these thalamo-cortical pathways. Certain qualitative features were common to both subdivisions; thus GABA-immunoreactive neurons were found in small clusters throughout the magnocellular and parvocellular divisions of the mediodorsal nucleus and, in addition, regions with few or no GABA-immunoreactive cells were often surrounded by strings of GABA-containing neurons.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synaptic activation of dendritic AMPA and NMDA receptors generates transient high-frequency firing in substantia nigra dopamine neurons in vitro

Transient high-frequency activity of substantia nigra dopamine neurons is critical for striatal synaptic plasticity and associative learning. However, the mechanisms underlying this mode of activity are poorly understood because, in contrast to other rapidly firing neurons, high-frequency activity is not evoked by somatic current injection. Previous studies have suggested that activation of dendritic N-methyl-D-aspartate (NMDA) receptors and/or G-protein-coupled receptor (GPCR)-mediated reduction of action potential afterhyperpolarization and/or activation of cation channels underlie high-frequency activity. To address their relative contribution, transient high-frequency activity was evoked using local electrical stimulation (1 s, 10–100 Hz) in brain slices prepared from p15–p25 rats in the presence of GABA and D2 dopamine receptor antagonists. The frequency, pattern, and morphology of action potentials evoked under these conditions were similar to those observed in vivo. Evoked activity and reductions in action potential afterhyperpolarization were diminished greatly by application of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or NMDA receptor selective antagonists and abolished completely by co-application of AMPA and NMDA antagonists. In contrast, application of glutamatergic and cholinergic GPCR antagonists moderately enhanced evoked activity. Dendritic pressure-pulse application of glutamate evoked high-frequency activity that was similarly sensitive to antagonism of AMPA or NMDA receptors. Taken together, these data suggest that dendritic AMPA and NMDA receptor-mediated synaptic conductances are sufficient to generate transient high-frequency activity in substantia nigra dopamine neurons by rapidly but transiently overwhelming the conductances underlying action potential afterhyperpolarization and/or engaging postsynaptic voltage-dependent ion channels in a manner that overcomes the limiting effects of afterhyperpolarization.