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At least 19 recordsLinked to original sources
PubMed1983

Substance P appears reduced in Huntington's disease: immunocytochemical findings in substantia nigra and substantia gelatinosa.

Using immunocytochemistry, this report visualizes immunoreactive substance P (SP) within human postmortem specimens of rostro-medial substantia nigra and dorsal spinal cord taken at autopsy from cases diagnosed as Huntington's disease (HD), and normal or non-HD. In the non-HD specimens of postmortem midbrain, the SP-immunoreaction products form a dense meshwork of neuronal processes throughout the substantia nigra (SN) pars compacta and pars reticulata. In the HD specimens, the SP-containing processes appear reduced. Presumably the reduced numbers of SP-containing processes result from the degeneration of parent SP perikarya located in the striatum, and cause the aberrant modulation of dopaminergic neurons which then influence basal ganglia output and therefore motor control. In the dorsal spinal cord substantia gelatinosa (SG), a nociceptive relay center, preliminary data demonstrate the reduced numbers of SP-containing processes in the HD cases compared with the non-HD cases. However neuronal degeneration is reportedly minimal in the spinal cord, and nociception in HD remains intact. Although the data require verification in SG, they suggest that certain kinds of neuronal degeneration may occur throughout the HD central nervous system. Additionally, the data imply that the role of SP in pain processing may require reevaluation.

Aged↗
PubMed2005

Visual receptive field properties of excitatory neurons in the substantia nigra.

The substantia nigra has been widely regarded as a structure involved in visuomotor co-ordination, but little is known about the sensory background of its function. Here we give a detailed description of the visual receptive field properties of excitatory substantia nigra neurons. The visual responses of 59 excitatory neurons were recorded in both the substantia nigra pars reticularis and the pars compacta of halothane-anesthetized, immobilized, artificially respirated cats. The substantia nigra neurons were not responsive or exhibited very low sensitivity to stationary visual stimulation. The units responded optimally to small stimuli moving at intermediate or high velocities in their extremely large receptive field. We observed no signs of retinotopical organization within the substantia nigra. A majority of the units exhibited narrow direction tuning and high direction selectivity, while a smaller proportion of them were broadly tuned and not direction-sensitive. Our results suggest that the visual properties of the excitatory substantia nigra units are quite similar to those of the superior colliculus and other extrastriatal structures that receive tectal afferents. This supports the notion that the substantia nigra processes dynamic visual information and that its excitatory visual neurons are modulated by the extrageniculate tectal visual system of the mammalian brain.

Action Potentials↗
PubMed1984

On the origin of dynorphin A and alpha-neo-endorphin in the substantia nigra.

The substantia nigra contains among the highest dynorphin A (Dyn A) and alpha-neo-endorphin (alpha-Neo) concentrations in the central nervous system. No dynorphin positive cell bodies are found there, only a dense network of nerve fibers and terminals. The present study provides evidence that the Dyn A and alpha-Neo in the substantia nigra are in neural processes arising from cells located in the head of the caudate nucleus. This neuronal system has been characterized by assaying Dyn A and alpha-Neo in the substantia nigra after a number of surgical transections of neuronal pathways in the rat forebrain and midbrain. Fibers containing dynorphins and neo-endorphins seem to pass through the internal capsule, ansa lenticularis, and medial forebrain bundle on their way from the striatum to the substantia nigra.

Animals↗
PubMed1986

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.

Action Potentials↗
PubMed1999

GABAergic control of rat substantia nigra dopaminergic neurons: role of globus pallidus and substantia nigra pars reticulata.

Dopaminergic neurons in vivo fire spontaneously in three distinct patterns or modes. It has previously been shown that the firing pattern of substantia nigra dopaminergic neurons can be differentially modulated by local application of GABA(A) and GABA(B) receptor antagonists. The GABA(A) antagonists, bicuculline or picrotoxin, greatly increase burst firing in dopaminergic neurons whereas GABA(B) antagonists cause a modest shift away from burst firing towards pacemaker-like firing. The three principal GABAergic inputs to nigral dopaminergic neurons arise from striatum, globus pallidus and from the axon collaterals of nigral pars reticulata projection neurons, each of which appear to act in vivo primarily on GABA(A) receptors (see preceding paper). In this study we attempted to determine on which afferent pathway(s) GABA(A) antagonists were acting to cause burst firing. Substantia nigra dopaminergic neurons were studied by single unit extracellular recordings in urethane anesthetized rats during pharmacologically induced inhibition and excitation of globus pallidus. Muscimol-induced inhibition of pallidal neurons produced an increase in the regularity of firing of nigral dopaminergic neurons together with a slight decrease in firing rate. Bicuculline-induced excitation of globus pallidus neurons produced a marked increase in burst firing together with a modest increase in firing rate. These changes in firing rate were in the opposite direction to what would be expected for a monosynaptic GABAergic pallidonigral input. Examination of the response of pars reticulata GABAergic neurons to similar manipulations of globus pallidus revealed that the firing rates of these neurons were much more sensitive to changes in globus pallidus neuron firing rate than dopaminergic neurons and that they responded in the opposite direction. Pallidal inhibition produced a dramatic increase in the firing rate of pars reticulata GABAergic neurons while pallidal excitation suppressed the spontaneous activity of pars reticulata GABAergic neurons. These data suggest that globus pallidus exerts significant control over the firing rate and pattern of substantia nigra dopaminergic neurons through a disynaptic pathway involving nigral pars reticulata GABAergic neurons and that at least one important way in which local application of bicuculline induces burst firing of dopaminergic neurons is by disinhibition of this tonic inhibitory input.

Action Potentials↗
PubMed1996

Blockade of dopamine storage, but not of dopamine synthesis, prevents activation of a tolbutamide-sensitive K+ channel in the guinea-pig substantia nigra.

The substantia nigra has one of the highest levels of ATP-sensitive K+ channel in the brain. Since this channel is controlled by cell metabolism, the aim of this study was to see how closely it is associated with nigral dopamine systems, which are decreased in Parkinson's disease. In a sub-population of neurons within the rostral substantia nigra pars compacta of the guinea-pig, a brief period of hypoxia resulted in a tolbutamide (100-500 microM) sensitive hyperpolarisation [input resistance (IR) decrease from 144.88 +/- 14.04 M omega pre-hypoxia to 105.91 +/- 13.25 M omega during hypoxia]. Maximal blockade of this decrease was seen in presence of 500 microns tolbutamide [IR decrease only from 161.35 +/- 32.82 M omega to 155.02 +/- 34.29 M omega]. Reserpine (which depletes dopamine stores) but not alpha-methyl-para-tyrosine (which decreases de novo synthesis of dopamine) caused a marked attenuation of this hyperpolarisation [IR decrease only from 163.32 +/- 44.42 M omega pre-hypoxia to 154.42 +/- 50.97 M omega during hypoxia]. This observation suggests that blockade of dopamine storage, but not of de novo synthesis, leads to a loss of responsiveness of certain mid-brain neurons to hypoxia, rendering them potentially more susceptible to subsequent degeneration. The possible link between nigral dopamine systems and ATP-sensitive K+ channels is discussed.

Animals↗
PubMed1985

Mechanisms of seizure control mediated by gamma-aminobutyric acid: role of the substantia nigra.

The substantia nigra has been identified as a critical site at which gamma-aminobutyric acid (GABA) agonist drugs act to reduce susceptibility to a number of types of experimentally induced generalized seizures. Moreover, the ability of systemically administered GABA-elevating agents to protect against maximal electroshock seizures is directly correlated with an increase in GABA specifically in the nerve-terminal compartment of substantia nigra. The significance of these findings is discussed in terms of the role of specific nigral synapses for the control of seizure propagation. Evidence from lesion studies, as well as studies with opiates and substance P analogs, further supports the hypothesis that Inhibition of nigral efferents reduces susceptibility to generalized seizures. Inhibition of nigral outflow causes a decreased sensitivity to chemoconvulsants without precluding the animal's ability to exhibit any or all of the motor components of a seizure. We therefore propose that nigral outputs are capable of facilitating seizure propagation and can function as a gating mechanism for the generalization of convulsive activity.

Animals↗
PubMed1993

GABAergic synaptic interactions in the substantia nigra.

The substantia nigra receives a strong GABAergic input from the ipsilateral striatum and globus pallidus. Nigral GABAergic synaptic interactions have been described in the pars compacta (SNC) and pars reticulata (SNR) but not in the pars lateralis (SNL). The SNR and particularly the SNL are the nodal points of the GABAergic nigrotectal pathway. The present study analyzes the synaptic connections of GABAergic and dopaminergic neurons in each of the divisions of the substantia nigra by employing a double-labeling immunocytochemical technique at the light and electron microscope levels. Glutamic acid decarboxylase (GAD)-containing terminals make symmetrical synaptic contacts with dopaminergic neurons in the SNC and SNR. Neurons that contain GAD also receive a GABAergic input in the SNR and SNL. The proportion of GAD-GAD contacts appears to be highest in the SNL where virtually all GAD-positive terminals are found to be in synaptic contact with or apposed to GAD positive profiles. This study demonstrates a strong GABAergic input onto nigral dopaminergic neurons and GABAergic neurons in the SNR and SNL. This GABAergic influence which is ostensibly striatal or pallidal in origin is particularly prominent in relation to the SNL-mediated nigro-collicular pathway.

Animals↗
PubMed2006

Sex- and cell-type-specific patterns of GABAA receptor and estradiol-mediated signaling in the immature rat substantia nigra.

The substantia nigra pars reticulata (SNR) is involved in movement and seizure control. In male but not female postnatal day 15 (PN15) rats, GABAA receptor agonists depolarize the SNR neurons and increase the expression of the calcium-regulated gene KCC2 (potassium/chloride cotransporter). Moreover, in PN15 rat SNR, 7beta-estradiol down-regulates KCC2 expression only in the presence of depolarizing GABAA receptor responses. The hypothesis tested here was that GABAA receptors and estradiol also regulate the expression of the phosphorylated form of the transcription factor cAMP responsive element binding protein (phosphoCREB), in PN15 rat SNR and substantia nigra pars compacta (SNC). Rats were injected with muscimol or 17beta-estradiol or their vehicles, and killed 1 h later. Sections were stained with an antibody specific for phosphoCREB alone or counterstained with either tyrosine hydroxylase (TH)- or parvalbumin (PRV)-specific antibodies. Muscimol increased phosphoCREB-ir in male but not in female SN neurons. Using gramicidin perforated patch clamp of PN14-15 SNC neuron, it was shown that muscimol bath application depolarized male SNC neurons but did not significantly alter membrane potential in females. In males, 17beta-estradiol decreased phosphoCREB expression in all studied cell types. In females, 17beta-estradiol did not influence phosphoCREB expression in PRV-ir SNR cells, but increased it in the dopaminergic SN neurons. These data suggest that GABAA receptor activation and estradiol promote the sexual differentiation of the SN in a cell-type-specific manner, by influencing calcium-regulated gene transcription, and therefore promoting the acquisition of sex-specific roles of the SN in movement and seizure control.

Animals↗
PubMed2001

Sexual dimorphism and developmental regulation of substantia nigra function.

The substantia nigra is an important brain nucleus involved in the expression of movement disorders and seizures. The two most common movement disorders affecting the substantia nigra, Parkinson's disease and Tourette syndrome, show gender differences and age-related onset. To assess the substrates for the gender and age specificity of substantia nigra-related disorders, we determined the functional properties of the substantia nigra gamma-aminobutyric acid (GABAA) system along its anterior-posterior axis, using localized microinfusions of muscimol (a GABAA agonist) and susceptibility to motor seizures in rats. In the substantia nigra, there are sex-specific differences in the topographic segregation and functionality of GABAA systems. In mature male rats there are two distinct regions mediating opposite effects on seizures; in female rats there is only one region that can affect seizures. In the neonatal period, the presence of circulating testosterone is essential for the development of a substantia nigra region that exerts proconvulsant effects throughout the rat's life, a unique feature of the male substantia nigra. The final maturation of the substantia nigra occurs in the peripubertal period, and is in part regulated by testosterone as well. The recognition of the existence of distinct sex- and age-specific substantia nigra features can be translated into new cures of disorders affecting the substantia nigra.

Aging↗
PubMed1987

Pertussis toxin blocks autoreceptor-mediated inhibition of dopaminergic neurons in rat substantia nigra.

Rat substantia nigra was injected with 1 microgram of purified pertussis toxin, a substance which inactivates the inhibitory guanine nucleotide regulatory unit of adenylate cyclase. In comparison to saline-injected animals, the pertussis toxin-treated animals showed almost no inhibition of dopaminergic neurons in response to dopamine applied iontophoretically or the dopamine agonist (-)-apomorphine given intravenously. These results provide evidence that a guanine nucleotide regulatory protein is involved as a transducer in mediating the physiological actions of dopamine autoreceptors.

Action Potentials↗
PubMed1995

Ontogeny and topography of seizure regulation by the substantia nigra.

The substantia nigra pars reticulata (SNR) is a structure involved in the control of seizures, and its effects on seizures are age-dependent. GABAergic transmission in the SNR, mediated by GABAA receptors, influences seizure susceptibility. We have found that in the adult SNR there may be at least two segregated GABAA-sensitive SNR projection networks involved in regulating the SNR effects on seizures, perhaps reflecting the existence of an anticonvulsant and a proconvulsant network. The two networks with opposing effects on seizures originate from two topographically distinct regions. The anterior-medial region of the SNR is associated with anticonvulsant effects, whereas the posterior-dorsal region of the SNR is associated with proconvulsant effects. To explain ontogenic differences in the SNR effects on seizures, we hypothesize that the two functionally segregated networks which influence the expression of seizures may become segregated with maturation. The increased seizure susceptibility of rat pups may be due, in part, to delayed development of this anterior-medial SNR anticonvulsant network.

Age Factors↗
PubMed1988

Intraneuronal dopamine in the primate substantia nigra.

The substantia nigra (SN) area compacta (AC) of primates was studied at various microscopic levels following treatment for the histo/cytochemical localization of dopamine (DA) in an effort to establish the intraneuronal loci of DA in neuron cell bodies. The method utilizes treatment of brain tissue slices in 4% glutaraldehyde in F12 buffer (pH 7.2) followed by 3% K2Cr2O7 (DC) in F12 buffer at pH 4.1. In this manner the glutaraldehyde (Glut)-DA product selectively reacts with DC to deposit chromium (Cr) at DA loci resulting in light and electron microscopic identification of DA in the perikarya of the AC. This selective technique has been analytically confirmed by in vitro model systems. The Cr accumulation within the tissues produces electron densities seen with the ordinary electron microscope whether viewed stained or unstained or with or without OsO4; however, the reactive areas are better studied without additional contrast chemicals. Examination of the densities with an energy dispersive x-ray analytical system (EDS) presents significant Cr readings and the degree of density can be correlated with the height of the Cr peak. Non-dense areas show either no Cr counts of only low background Cr values. Endogenous elements with higher than background values identified along with the exogenous Cr are chlorine (Cl) and sulfur (S) and phosphorous (P). Only particular neurons of the AC possess the Cr positive DA reactivity. It is apparent that the Cr positive organelles differ structurally from organelles in non-DA neurons. There appear to be DA organelles specific to particular SN neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Expression of substance P receptor in the substantia nigra.

Since the substantia nigra receives abundant substance P innervations but lacks clear evidences about a presence of substance P receptors, expressions for mRNA and protein of substance P receptors were investigated in the rat to resolve this mismatch. Expression levels of substance P receptors mRNA in the substantia nigra pars compacta and reticulata were 37.7 and 24.1% of those in the striatum, respectively, by reverse transcription-polymerase chain reaction (RT-PCR). Substance P receptors mRNA was found in dopamine neurons of the substantia nigra pars compacta by single cell RT-PCR. Ca. 90% of dopamine neurons in the substantia nigra pars compacta were immunoreactive to anti-substance P receptor antibody in the colchicine treated rats. These are the first direct evidence for the existence of substance P receptors in dopamine neurons of the substantia nigra pars compacta.

Animals↗
PubMed1985

Evidence for dopamine release and metabolism beyond the control of nerve impulses and dopamine receptors in rat substantia nigra.

In rat substantia nigra a biphasic disappearance curve of dopamine (DA) was seen after tyrosine hydroxylase inhibition by alpha-methyl-p-tyrosine (alpha-MT): the initial phase had a fast turnover and a half life of 0.5 h and the later phase had an extremely slow turnover. In contrast to the effects in striatum, neither haloperidol nor apomorphine influenced alpha-MT-induced DA disappearance in the substantia nigra. Furthermore, inhibition of impulse flow by gamma-butyrolactone prevented DA disappearance in striatum but not in the substantia nigra. Measurements of DA and 3-methoxytyramine following treatment with inhibitors of monoamine oxidase (pargyline) and catechol-O-methyl transferase (tropolone) indicated that O-methylation is a more important metabolic pathway in the substantia nigra than in the striatum. The data are interpreted to indicate that the release and metabolism of DA in the substantia nigra are largely beyond the control of nerve impulses and DA receptors. It is suggested that such an arrangement forms an important feature of autoreceptor-mediated feedback control of DA nerve cell activity.

4-Butyrolactone↗
PubMed1994

The subthalamo-nigral pathway regulates movement and concomitant acetylcholinesterase release from the substantia nigra.

Within the substantia nigra acetylcholinesterase is released independently of cholinergic transmission: this release could be related to some aspects of motor control. To investigate this possibility, acetylcholinesterase release was continuously monitored in relation to specific movements evoked by central electrical stimulation. Increased intensities of stimulation of the subthalamic nucleus in awake guinea-pigs produced a behavioural response, ranging from a decrease in spontaneous movement, to chewing, to both chewing and circling movements. Enhancement of acetylcholinesterase release occurred only when large scale movements (circling as well as chewing) were evoked by subthalamic stimulation: however, a similar protocol of stimulation during ketamine-induced anaesthesia did not produce any comparable movements nor any concomitant change in the release of acetylcholinesterase. Perfusion of the glutamate agonist N-methyl-D-aspartate (NMDA) into the substantia nigra also induced an increase in release of acetylcholinesterase from the substantia nigra of conscious animals, whereas (S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) did not significantly enhance acetylcholinesterase levels. It is concluded that AChE release in the substantia nigra can occur as a result of activation of glutamatergic subthalamic afferents, and that this activation may also be associated with changes in movement.

Acetylcholinesterase↗
PubMed2001

Activation of metabotropic glutamate receptor 1 inhibits glutamatergic transmission in the substantia nigra pars reticulata.

The substantia nigra pars reticulata is a primary output nucleus of the basal ganglia motor circuit and is controlled by a fine balance between excitatory and inhibitory inputs. The major excitatory input to GABAergic neurons in the substantia nigra arises from glutamatergic neurons in the subthalamic nucleus, whereas inhibitory inputs arise mainly from the striatum and the globus pallidus. Anatomical studies revealed that metabotropic glutamate receptors (mGluRs) are highly expressed throughout the basal ganglia. Interestingly, mRNA for group I mGluRs are abundant in neurons of the subthalamic nucleus and the substantia nigra pars reticulata. Thus, it is possible that group I mGluRs play a role in the modulation of glutamatergic synaptic transmission at excitatory subthalamonigral synapses. To test this hypothesis, we investigated the effects of group I mGluR activation on excitatory synaptic transmission in putative GABAergic neurons in the substantia nigra pars reticulata using the whole cell patch clamp recording approach in slices of rat midbrain. We report that activation of group I mGluRs by the selective agonist (R,S)-3,5-dihydroxyphenylglycine (100 microM) decreases synaptic transmission at excitatory synapses in the substantia nigra pars reticulata. This effect is selectively mediated by presynaptic activation of the group I mGluR subtype, mGluR1. Consistent with these data, electron microscopic immunocytochemical studies demonstrate the localization of mGluR1a at presynaptic sites in the rat substantia nigra pars reticulata. From this finding that group I mGluRs modulate the major excitatory inputs to GABAergic neurons in the substantia nigra pars reticulata we suggest that these receptors may play an important role in basal ganglia functions. Studying this effect, therefore, provides new insights into the modulatory role of glutamate in basal ganglia output nuclei in physiological and pathophysiological conditions.

Animals↗