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At least 19 recordsLinked to original sources
PubMed1997

Parvalbumin and calbindin D-28k in the entopeduncular nucleus, subthalamic nucleus, and substantia nigra of the rat as revealed by double-immunohistochemical methods.

The cellular localization of calbindin D-28k (CB) and parvalbumin (PV) was analyzed by means of double-immunohistochemical techniques applied to single sections in the entopeduncular nucleus (EP), the subthalamic nucleus (STh), and the substantia nigra (SN) of the rat. In EP, PV-positive cells abounded centrally, where CB immunostaining was minimal. The medial and ventral sectors of EP were markedly enriched with CB neuropil but devoid of PV-positive cells. CB-positive neurons abounded particularly in the rostral pole of EP. In STh, PV-positive neurons and neuropil were concentrated in the lateral two thirds of this nucleus. Only a few PV-positive cells were detected in sectors of STh devoid of PV-positive neuropil. The STh was completely devoid of CB immunostaining. In the rostral two thirds of SN, PV-positive neurons were largely confined to the lateral half of the pars reticulata (SNR), and occurred more ventrally and medially in the caudal third. Intense CB-immunoreactive neuropil was found in medial and dorsal parts of rostral SNR, and CB-positive cells were observed in the SN pars compacta and the ventral tegmental area. PV and CB cells were also observed in the pars lateralis of SN. The markedly heterogeneous pattern of distribution of PV and CB in EP, STh, and SN suggests that these two calcium-binding proteins may label distinct functional domains in each of these three components of the rat basal ganglia.

Animals↗
PubMed1997

Synaptic integration of functionally diverse pallidal information in the entopeduncular nucleus and subthalamic nucleus in the rat.

To determine the principles of synaptic innervation of neurons in the entopeduncular nucleus and subthalamic nucleus by neurons of functionally distinct regions of the pallidal complex, double anterograde labeling was carried out at both light and electron microscopic levels in the rat. Deposits of the anterograde tracers Phaseolus vulgaris-leucoagglutinin and biotinylated dextran amine were placed in different functional domains of the pallidal complex in the same animals. The tracer deposits in the ventral pallidum and the globus pallidus gave rise to GABA-immunopositive projections to the entopeduncular nucleus, the subthalamic nucleus, and the more medial lateral hypothalamus that were largely segregated but overlapped at the interface between the two fields of projection. In these regions the proximal parts of individual neurons in the entopeduncular nucleus, lateral hypothalamus, and subthalamic nucleus received synaptic input from terminals derived from both the ventral pallidum and the globus pallidus. Furthermore, the analysis of the afferent synaptic input to the dendrites of neurons in the subthalamic nucleus that cross functional boundaries of the nucleus defined by the pallidal inputs, revealed that terminals with the morphological and neurochemical characteristics of those derived from the pallidal complex make synaptic contact with all parts of the dendritic tree, including distal regions. It is concluded that functionally diverse information carried by the descending projections of the pallidal complex is synaptically integrated by neurons of the entopeduncular nucleus, lateral hypothalamus, and subthalamic nucleus by two mechanisms. First, neurons located at the interface between functionally distinct, but topographically adjacent, projections could integrate diverse information by means of the synaptic convergence at the level of the cell body and proximal dendrites. Second, because the distal dendrites of neurons in the subthalamic nucleus receive input from the pallidum, those that extend across two distinct domains of pallidal input could also provide the morphological basis of integration.

Afferent Pathways↗
PubMed1997

Glutamate-enriched cholinergic synaptic terminals in the entopeduncular nucleus and subthalamic nucleus of the rat.

Several lines of evidence suggest that the cholinergic neurons of the mesopontine tegmentum contain elevated levels of glutamate and are the source of cholinergic terminals in the subthalamic nucleus and entopeduncular nucleus. The object of this study was to test whether cholinergic terminals in the entopeduncular nucleus and subthalamic nucleus, also express relatively high levels of glutamate. To address this, double immunocytochemistry was performed at the electron microscopic level. Perfuse-fixed sections of rat brain were immunolabelled to reveal choline acetyltransferase by the pre-embedding avidin-biotin-peroxidase method. Serial ultrathin sections of cholinergic terminals in both the entoped uncular nucleus and subthalamic nucleus were then subjected to post-embedding immunocytochemistry to reveal glutamate and GABA. Quantification of the immunogold labelling showed that choline acetyltransferase-immunopositive terminals and boutons in both regions were significantly enriched in glutamate immunoreactivity and had significantly lower levels of GABA immunoreactivity in comparison to identified GABAergic terminals. Furthermore, the presumed transmitter pool of glutamate i.e. that associated with synaptic vesicles, was significantly greater in the choline acetyltransferase-positive terminals than identified GABA terminals, albeit significantly lower than in established glutamatergic terminals. In the entopeduncular nucleus, a small proportion of cholinergic terminals displayed high levels of GABA immunoreactivity. Taken together with other immunocytochemical and tracing data, the elevated levels of glutamate in cholinergic terminals in the entopeduncular nucleus and subthalamic nucleus, is further evidence adding weight to the suggestion that acetylcholine and glutamate may be co-localized in both the perikarya and terminals of at least a proportion of neurons of the mesopontine tegmentum.

Animals↗
PubMed2007

Mortality in patients with Parkinson's disease treated by stimulation of the subthalamic nucleus.

Subthalamic nucleus (STN) stimulation improves motor disability and quality of life in patients with advanced Parkinson's disease (PD). Short-term mortality is low, but little is known about long-term mortality. We assessed mortality and causes of death in 171 consecutive PD patients treated by STN stimulation. Surgery was performed after a median lagtime of 13 years from PD onset at a median age of 57 years. The median follow-up after surgery was 41 months. Sixteen patients died 8 to 83 months after neurosurgery. Poorer cognitive function was the only predictive factor for mortality (standardized mortality ratio = 2.9; 95% confidence interval [CI], 1.6-4.7; P < 0.0001). Based on a historical comparison of 118 operated patients with 39 nonoperated patients from a different population, survival among operated patients was not better (hazard ratio = 1.2; 95% CI, 0.7-2.1).

Adult↗
PubMed2002

High-frequency stimulation of the subthalamic nucleus silences subthalamic neurons: a possible cellular mechanism in Parkinson's disease.

The subthalamic nucleus participates in the control of movement and is considered a surgical target in the treatment of parkinsonian symptoms. Using the rat brain in vitro slice technique we show that sustained high-frequency (>100 Hz) electrical stimulation (i.e., 'tetanic stimulation') of the nucleus, as used in humans to treat Parkinson's disease, silenced subthalamic neurons. Two main cell types were identified. 'Tonic cells' (68%) showed delayed inward rectification, fired continuously, switched to bursting and stopped firing when strongly depolarized with injected current. Tetanic stimulation of the nucleus induced a steady depolarization (approximately 18 mV) that triggered action potentials at a high rate followed by bursts and finally (approximately 25 s) totally silenced tonic cells. The control tonic activity was recovered rapidly (<10 s) after ending stimulation. 'Phasic cells' (25%) discharged a single initial brief burst of action potentials both when depolarized by prolonged current injection and tetanic stimulation and did not show inward rectification. An infrequent cell type called 'phasic-tonic' (7%) showed a mixed discharge. We suggest that the silencing effect of tetanic stimulation is not a frequency-dependent presynaptic depression and could result from the gradual inactivation of Na+-mediated action potentials. These findings suggest that the remission of parkinsonian symptoms by treatment with high-frequency electrical stimulation of the subthalamic nucleus in humans may primarily reside on its capacity to suppress the action potential activity of subthalamic neurons.

Action Potentials↗
PubMed2006

Conventional MRI is inadequate to delineate the relationship between the red nucleus and subthalamic nucleus in Parkinson's disease.

BACKGROUND: An understanding of the relationships between the anterior commissure-posterior commissure line (AC-PC), the subthalamic nucleus (STN), and red nucleus (RN) is imperative if these structures are to be used for targeting in deep brain stimulation. Currently, these relationships are incompletely understood and difficult to assess using conventional MRI. We examined the location and relationships of the STN and the RN to the AC-PC line and to each other in order to provide a greater understanding of their utility when targeting the STN, and the consistency of these anatomic relationships when examined using conventional MRI. METHODS: A total of 52 STN and RN in 26 patients with Parkinson's disease were evaluated on T2-weighted MR images. The anterior and posterior commissures and the border coordinates of the STN and RN were derived using frame coordinates. The distances from the midcommissural point (mcp) to the centers of the STN and RN, the diameters for each nucleus, and the distances between the nuclei were calculated in the x-, y-, and z-axes. RESULTS: The mean AC-PC length was 26.1 +/- 1.3 mm. The distance from the mcp to the center of the STN was 10 +/- 0.7 mm in the x-axis, 0.2 +/- 0.7 mm in the y-axis, and 3.3 +/- 0.9 mm in the z-axis. The distance from the mcp to the center of the RN was 4.7 +/- 0.6 mm in the x-axis, -5.9 +/- 1.0 mm in the y-axis, and 6.1 +/- 1.3 mm in the z-axis. The distance between the STN and RN was 2.3 +/- 0.7 mm in the x-axis, 2.1 +/- 1.0 mm in the y-axis, and -0.2 +/- 1.3 mm in the z-axis. CONCLUSIONS: Although recent studies imply that the RN can be used as a relatively consistent marker for the position of the STN, the present data suggest otherwise. These data indicate that a single targeting method may be inadequate given the resolution of conventional MRI, and that it is imperative to use multiple anatomical measurements when targeting the STN for deep brain stimulation in Parkinson's disease.

Deep Brain Stimulation↗
PubMed2003

Effect of high-frequency stimulation of the subthalamic nucleus on subthalamic neurons: an intracellular study.

BACKGROUND/AIMS: The precise mechanism of action of deep brain stimulation in the subthalamic nucleus (STN) for the treatment of Parkinson's disease and epilepsy is unknown. In the present study, the intracellular effects on STN neurons following high-frequency stimulation (HFS) of STN were examined to test the hypothesis that HFS results in either an increase or a decrease in neuronal action potential generation. METHODS: Intracellular electrophysiological recordings were made in the rat STN neurons in in vitro slice preparations. A concentric bipolar stimulating electrode was placed in the STN, and electrical stimulation (duration, 100-2000 ms; amplitude, 10-500 microA, and frequency, 10-200 Hz) was delivered while simultaneously recording intracellularly from a STN neuron using a sharp electrode. RESULTS: HFS of STN resulted in the generation of excitatory postsynaptic potentials and an increase in action potential firing during the stimulation period followed by a period of poststimulation inhibition of firing in STN neurons. The degree of increase in action potentials from HFS was critically dependent on the frequency of electrical stimulation, i.e. at approximately 100-140 Hz, maximal increase was obtained, but at 200 Hz, the activity was blocked. Interestingly, the duration of poststimulation inhibition of firing was dependent on the duration of stimulation, i.e. the longer the HFS, the longer the inhibition. CONCLUSIONS: These results suggest that the mechanism of action of deep brain stimulation involves initial excitation followed by later inhibition of STN neurons at a cellular level rather than primary inhibition, as previously hypothesized.

Action Potentials↗
PubMed1998

Distribution of glutamate receptor subunits at neurochemically characterized synapses in the entopeduncular nucleus and subthalamic nucleus of the rat.

Glutamatergic neurotransmission in the subthalamic nucleus (STN) and in the output nuclei of the basal ganglia is critical in the expression of basal ganglia function, and increased glutamate transmission in these nuclei has been implicated in the pathology of Parkinson's disease. In order to determine the precise spatial relationship of subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors to nerve terminals enriched in glutamate or gamma-aminobutyric acid (GABA) in one of the output nuclei, the entopeduncular nucleus (EP), and the STN, postembedding immunolabelling for glutamate receptor subunits and for glutamate and GABA was carried out in the rat. Immunolabelling for the AMPA glutamate receptor subunits 1, 2/3, and 4 (GluR1, GluR2/3, and GluR4) and the NMDA receptor subunit 1 (NR1) was localized predominantly within asymmetrical synapses in both the EP and STN. Quantitative analysis revealed that, on average for the whole population, each of the receptor subunits was evenly distributed along the synaptic specialization. Multiple AMPA receptor subunits and the GluR2/3 and NMDA (NR1) subunits were co-localized within individual synapses. The combination of immunolabelling for glutamate and GABA with the receptor immunolabelling revealed that the majority of axon terminals presynaptic to the receptor-immunoreactive synapses were enriched in glutamate immunoreactivity and were GABA-immunonegative. However, at some NR1- and GluR2/3-positive synapses, the level of glutamate immunoreactivity was low in the presynaptic terminal and, in the STN, some of them were GABA-immunopositive. It is concluded that glutamatergic transmission at individual synapses of different origins in the EP and STN is mediated by a combination ofAMPA and NMDA glutamate receptors.

Animals↗
PubMed1994

The projections from the parafascicular thalamic nucleus to the subthalamic nucleus and the striatum arise from separate neuronal populations: a comparison with the corticostriatal and corticosubthalamic efferents in a retrograde fluorescent double-labelling study.

The parafascicular thalamic nucleus projects to the subthalamic nucleus and the striatum. Double-retrograde fluorescent tracing was used to determine whether these projections arise from the same neurons via axon collaterals. True Blue was injected into the subthalamic nucleus and Nuclear Yellow was injected into the striatum of each rat and the parafascicular thalamic nucleus was examined under the fluorescence light-microscope. Individual parafascicular neurons were not double-labelled with the tracers. The True Blue- and Nuclear Yellow-labelled neurons wee located in different parts of the parafascicular nucleus ipsilateral to the injections. In the rostral part of the parafascicular nucleus, True Blue-labelled neurons were located ventral to the fasciculus retroflexus, and in the caudal part of the nucleus. True Blue-labelled neurons were located close to the medial and lateral borders of fasciculus retroflexus. Nuclear Yellow-labelled neurons were found mainly to encircle the fasciculus retroflexus in the rostral part of the parafascicular nucleus and in the dorsolateral sector of the caudal part of the parafascicular nucleus. Double-labelled neurons were, however, found in the cortex. The proportion of neurons projecting to both the subthalamic nucleus and the striatum accounted for 38% of the total number of cortiscosubthalamic neurons in the prefrontal cortex, 15.5% in the cingulate cortex and 9% in the sensorimotor cortex. The present finding of an individualization between the parafascicular efferents to the subthalamic nucleus and the striatum emphasize the importance of this projection and provides further evidence of the associative functions attributable to the subthalamic nucleus.

Animals↗
PubMed2003

Electrophysiological and metabolic evidence that high-frequency stimulation of the subthalamic nucleus bridles neuronal activity in the subthalamic nucleus and the substantia nigra reticulata.

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) has been shown to produce a dramatic alleviation of motor symptoms in patients with advanced Parkinson's disease. Its functional mechanism, however, remains obscure. We used extracellular recording and in situ cytochrome oxidase (CoI) mRNA hybridization to investigate the effects of HFS of the STN on neuronal activity of the STN and the substantia nigra reticulata (SNr) in normal rats and rats with 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra compacta (SNc). To allow detection of spikes and analysis of firing activity, artifacts recorded during stimulation were scaled down using a template subtraction method. In both normal and lesioned rats, the activity of a majority of STN neurons was inhibited during stimulation. In the SNr, HFS also induced an inhibition of the activity of a majority of neurons in normal and lesioned rats. In situ hybridization histochemistry confirmed these results in that it showed a significant decrease in levels of CoI mRNA expression in the STN and SNr in both normal and lesioned rats during stimulation. These data afford an interesting insight into the functional mechanism of deep brain stimulation and support the hypothesis that HFS exerts an inhibitory influence on STN neuronal firing.

Animals↗
PubMed2000

Morphological study of the tegmental pedunculopontine nucleus, substantia nigra and subthalamic nucleus, and their interconnections in rat organotypic culture.

The morphological organization of the tegmental pedunculopontine nucleus, midbrain extrapyramidal area, substantia nigra and subthalamic nucleus and their interrelationships were studied in rat organotypic culture using immunohistochemistry and NADPH-diaphorase histochemistry. Three coronal sections, one containing the tegmental pedunculopontine nucleus/midbrain extrapyramidal area, another with the substantia nigra and the third with the subthalamic nucleus, were obtained from postnatal 1-2-day-old rats. These sections were co-cultured for 3-4 weeks using the roller-tube technique. In the tegmental pedunculopontine nucleus/midbrain extrapyramidal area, the distribution pattern of cholinergic neurons was similar to that found in the in vivo study. We could, therefore, identify the subdivisions of the tegmental pedunculopontine nucleus (i.e., pars compacta and pars dissipata) and the midbrain extrapyramidal area. As in the in vivo situation, glutamate immunoreactive neurons were also located in these areas. Approximately 10% of NADPH-diaphorase positive neurons in the tegmental pedunculopontine nucleus, were glutamate immunoreactive. In the substantia nigra, as in the in vivo, tyrosine hydroxylase immunoreactive (putative dopaminergic) neurons were identified predominantly in the substantia nigra pars compacta, and parvalbumin immunoreactive neurons (putative GABAergic) mainly in the substantia nigra pars reticulata. The subthalamic nucleus was ladened with glutamate immunoreactive neurons. NADPH-diaphorase stained axons originating from the tegmental pedunculopontine nucleus were traced into the substantia nigra and subthalamic nucleus. They were often in close apposition to tyrosine hydroxylase immunoreactive neurons in the substantia nigra. Parvalbumin immunoreactive fibers from the substantia nigra projected heavily to the midbrain extrapyramidal area, but only sparsely to the tegmental pedunculopontine nucleus and the subthalamic nucleus. These findings indicate that the tegmental pedunculopontine nucleus/midbrain extrapyramidal area, substantia nigra and subthalamic nucleus in the organotypic culture have retained a basic morphological organization and connectivity similar to those seen in the in vivo situation. Therefore, this preparation could be a useful model to conduct further studies to investigate functional circuits among the structures represented.

Animals↗
PubMed1998

Ipsilateral turning behavior induced by unilateral microinjections of a cannabinoid into the rat subthalamic nucleus.

The subthalamic nucleus contains cannabinoid receptors and cannabinoid receptor mRNA. However, the role of cannabinoid receptors in this nucleus has not been examined. In order to investigate the functional role of cannabinoid receptors in the rat subthalamic nucleus, turning activity was observed following unilateral microinjection of the synthetic cannabinoid CP 55,940. CP 55,940 (10 microg) induced ipsilateral turning. This effect was blocked by coadministration of the cannabinoid receptor antagonist SR141716A (5 microg). These results suggest that cannabinoid receptors in the subthalamic nucleus mediate an inhibition of motor activity.

Animals↗
PubMed1994

Lesions of the entopeduncular nucleus and the subthalamic nucleus reduce dopamine receptor antagonist-induced catalepsy in the rat.

The role of the entopeduncular nucleus (EP) and the subthalamic nucleus (STN) in mediating dopamine receptor antagonist-induced catalepsy in the rat was investigated. Five days after bilateral lesions of EP and STN respectively with the excitotoxin quinolinic acid (15, 30 nmol/0.5 microliter/side and 24 nmol/0.5 microliter/side, respectively) rats were injected intraperitoneally with the dopamine D1 receptor antagonist SCH 23390 (0.5 mg/kg) or the dopamine D2 receptor antagonist haloperidol (0.5 mg/kg). Complete EP lesions prevented both SCH 23390- and haloperidol-induced catalepsy. STN lesions exerted pronounced anticataleptic effects in case of haloperidol-induced catalepsy, but less pronounced in case of SCH 233390-induced catalepsy. Further characterization of these anticataleptic effects in an open field demonstrated, that neither EP- nor STN lesions reversed bradykinesia, which occurred after selective dopamine receptor blockade. In conclusion, both EP and STN participate in the mediation of catalepsy induced by dopamine D1- and dopamine D2 receptor antagonists. Thereby these nuclei preferentially mediate rigidity and akinesia, but to a lesser extent bradykinesia.

Animals↗
PubMed1992

Cholinergic innervation of the human striatum, globus pallidus, subthalamic nucleus, substantia nigra, and red nucleus.

The anatomical organization of cholinergic markers such as acetylcholinesterase, choline acetyltransferase, and nerve growth factor receptors was investigated in the basal ganglia of the human brain. The distribution of choline acetyltransferase-immunoreactive axons and varicosities and their relationship to regional perikarya showed that the caudate, putamen, nucleus accumbens, olfactory tubercle, globus pallidus, substantia nigra, red nucleus, and subthalamic nucleus of the human brain receive widespread cholinergic innervation. Components of the striatum (i.e., the putamen, caudate, olfactory tubercle, and nucleus accumbens) displayed the highest density of cholinergic varicosities. The next highest density of cholinergic innervation was detected in the red nucleus and subthalamic nucleus. The level of cholinergic innervation was of intermediate density in the globus pallidus and the ventral tegmental area and low in the pars compacta of the substantia nigra. Immunoreactivity for nerve growth factor receptors (NGFr) was confined to the cholinergic neurons of the basal forebrain and their processes. Axonal immunoreactivity for NGFr was therefore used as a marker for cholinergic projections originating from the basal forebrain (Woolf et al., '89: Neuroscience 30:143-152). Although the vast majority of striatal cholinergic innervation was NGFr-negative and, therefore, intrinsic, the striatum also contained NGFr-positive axons, indicating the existence of an additional cholinergic input from the basal forebrain. This basal forebrain cholinergic innervation was more pronounced in the putamen than in the caudate. The distribution of NGFr-positive axons suggested that the basal forebrain may also project to the globus pallidus but probably not to the subthalamic nucleus, substantia nigra, or red nucleus. The great majority of cholinergic innervation to these latter three structures and to parts of the globus pallidus appeared to come from cholinergic neurons outside the basal forebrain, most of which are probably located in the upper brainstem. These observations indicate that cholinergic neurotransmission originating from multiple sources is likely to play an important role in the diverse motor and behavioral affiliations that have been attributed to the human basal ganglia.

Acetylcholinesterase↗
PubMed1982

Electron microscopy of the subthalamic nucleus in the baboon. I. Synaptic organization of the subthalamic nucleus in the baboon.

Our study of the synaptic organization of the baboon subthalamic nucleus has revealed at least nine different types of synapses. Most frequently encountered is the type I (F) axo-dendritic or axo-somatic synapse. It is characterized by scattered flat vesicles and many large mitochondria. The axon terminal is either elongated, tubule shaped (type IF en passant), and undergoes many short button-like en passant junctions with a parallel running dendrite, or it is spindle shaped with similar synaptic contacts (type IFa). In other cases a more compact bouton forms many short junctions at the same time with a dendrite and a beak-shaped spine springing from it. A smaller bouton with flat vesicles, which show a tendency to fuse together (type IIF) usually undergoes slightly asymmetric contacts with two vesicles-free dendrites between which they frequently appear wedged. Three types of boutons with small, round vesicles have extended asymmetric contacts forming elongated (type III), star-shaped (type IV), or oval (type V) synapses. The latter form contacts mostly with dendritic terminals or spines. Another type of synapses contain larger, pale, pleomorphic vesicles (VI (SO)): The bouton is more compact and often in contact with a dendritic terminal. Type VII (LO) shows a looser arrangement of vesicles intermingled with more dense core vesicles. Type VIII (F) is a dendritic terminal with loosely arranged, flat vesicles and is in contact either with a type VI or with a type VII P bouton. Finally, there is an axo-spinous microsynapse type IX, which partly degenerates after contralateral pallidum externum coagulation. A few axon preterminals filled with dense core vesicles do not undergo synaptic contacts.

Animals↗
PubMed2003

A model of reverse spike frequency adaptation and repetitive firing of subthalamic nucleus neurons.

Subthalamic nucleus neurons exhibit reverse spike-frequency adaptation. This occurs only at firing rates of 20-50 spikes/s and higher. Over this same frequency range, there is an increase in the steady-state frequency-intensity (F-I) curve's slope (the secondary range). Specific blockade of high-voltage activated calcium currents reduced the F-I curve slope and reverse adaptation. Blockade of calcium-dependent potassium current enhanced secondary range firing. A simple model that exhibited these properties used spike-triggered conductances similar to those in subthalamic neurons. It showed: 1) Nonaccumulating spike afterhyperpolarizations produce positively accelerating F-I curves and spike-frequency adaptation that is complete after the second spike. 2) Combinations of accumulating aftercurrents result in a linear F-I curve, whose slope depends on the relative contributions of inward and outward currents. Spike-frequency adaptation can be gradual. 3) With both accumulating and nonaccumulating aftercurrents, primary and secondary ranges will be present in the F-I curve. The slope of the primary range is determined by the nonaccumulating conductance; the accumulating conductances govern the secondary range. The transition is determined by the relative strengths of accumulating and nonaccumulating currents. 4) Spike-threshold accommodation contributes to the secondary range, reducing its slope at high firing rates. Threshold accommodation can stabilize firing when inward aftercurrents exceed outward ones. 5) Steady-state reverse adaptation results when accumulated inward aftercurrents exceed outward ones. This requires spike-threshold accommodation. Transient speedup arises when inward currents are smaller than outward ones at steady state, but accumulate more rapidly. 6) The same mechanisms alter firing in response to irregular patterns of synaptic conductances, as cell excitability fluctuates with changes in firing rate.

Adaptation, Physiological↗
PubMed2005

GABAergic interneurons in human subthalamic nucleus.

The subthalamic nucleus (STN) is considered a homogeneous structure composed essentially of projection neurons that exert a profound glutamate-mediated excitatory influence upon the main output structures of the basal ganglia. It is currently the most efficient target for deep brain stimulations designed to alleviate symptoms of Parkinson's disease. STN neurons were analyzed by applying stereological methods and single/double-immunostaining procedures to postmortem material obtained from normal individuals. Besides a multitude of closely packed projection neurons ( approximately 24.7 mum in diameter), the human STN (mean volume, 174.5 +/- 20.4 mm3; total neuronal density, 239.5 +/- 31.9 x 10(3)) contained smaller neurons (approximately 12.2 microm), which displayed glutamic acid decarboxylase (GAD)(65/67) immunoreactivity and shared the morphological features of interneurons described in Golgi studies of primate STN. These putative gamma-aminobutyric acid (GABA)ergic interneurons accounted for 7.5% of the total neuronal population of the STN. Although present throughout the nucleus, they were significantly more numerous in its posterior-ventral-medial sector, which belongs to the limbic/associative functional territory. Many projection neurons located dorsolaterally in the STN showed parvalbumin immunoreactivity and others lying ventromedially displayed calretinin immunostaining, but none of the GAD-positive interneurons expressed these calcium-binding proteins. Although less abundant than projection neurons, GABAergic interneurons might play a important role in the intrinsic organization of the STN. The morphological and chemical heterogeneity of the human STN reported here might have important implications in the functional organization of the basal ganglia.

Adult↗
PubMed2003

Spontaneous and evoked activity of substantia nigra pars reticulata neurons during high-frequency stimulation of the subthalamic nucleus.

The subthalamic nucleus (STN), a major component of the basal ganglia, exerts an excitatory influence on the output structures of this system i.e., the substantia nigra pars reticulata (SNR) and the internal segment of the globus pallidus. High-frequency stimulation of the STN is a method currently used to treat parkinsonian symptoms. The aim of the present study was to analyze the effects of STN high-frequency stimulation on the activity of SNR neurons and to investigate its impact on the transfer of information between the cerebral cortex and the SNR. During STN high-frequency stimulation, the activity of SNR cells was decreased at low-intensity stimulation, whereas it was increased at a higher intensity. The decrease in the discharge of SNR cells likely results from the activation of a GABAergic transmission in the SNR because this effect was blocked by local application of bicuculline. The increased activity likely results from the activation of the glutamatergic subthalamonigral projection because the latency of the evoked excitations was consistent with the conduction time of the subthalamonigral neurons. Finally, during STN high-frequency stimulation, the transmission of cortical information along the direct trans-striatal pathway was preserved, whereas the functionality of the trans-subthalamic pathways was partly preserved or completely blocked depending on the stimulation intensity. The present data indicate that STN high-frequency stimulation influences the activity of SNR cells through activation of their excitatory and inhibitory synaptic afferent pathways as well as antidromic activation of the projection neurons.

Action Potentials↗