Biomedical subjects

S T Kitai

Publications and source records attributed to S T Kitai.

At least 55 records · Page 3Linked to original sources

PubMed1992

Patterns of termination of cerebellar and basal ganglia efferents in the rat thalamus. Strictly segregated and partly overlapping projections.

There is a widely held view that the cerebellum and basal ganglia act via separate subcortical channels. In rodent, however, electrophysiological evidence suggests that the output of these two systems is partly sent to a common set of thalamic neurons. In this study, the pattern of thalamic innervations provided by the deep cerebellar nuclei, the entopeduncular nucleus, and the substantia nigra pars reticulata was reinvestigated in the rat using the anterograde tracers Phaseolus vulgaris leucoagglutinin and wheat germ agglutinin. Although the results confirm the existence of some overlap in the cerebellar and basal ganglia projection fields, they also show that in such convergent areas the cerebellar innervation is modest and consists of sparsely distributed fibers of thin diameter that provide a few scattered terminal boutons. These observations are consistent with the view that, in rodent as in higher mammalian species, the cerebellum and the basal ganglia act mainly via distinct thalamo-cortical channels.

Animals↗

PubMed1992

Flunarizine induces a transient loss of tyrosine hydroxylase immunoreactivity in nigrostriatal neurons.

Neurotoxic effects of flunarizine (Fz), a selective calcium channel blocker, on the nigrostriatal dopamine system was investigated. Systemic injections of Fz to mice resulted in a transient loss of tyrosine hydroxylase (TH) immunoreactive nigrostriatal neurons without cell loss. TH immunoreactivity in these neurons was greatly reduced as rapidly as one day after drug administration (regardless of dosage used) and thereafter recovered in both dose- and time-dependent manners. Such a novel neurotoxic action of Fz may constitute a morphological substrate for reversible drug-induced parkinsonian signs described in recent clinical case reports.

Animals↗

PubMed1992

Single-unit activity in the globus pallidus and neostriatum of the rat during performance of a trained head movement.

Single-unit extracellular neuronal recordings were obtained from the globus pallidus (GP) and the neostriatum (NS) of rats while they performed a learned head movement in response to an auditory cue. In both GP and NS, units that altered their discharge rate in association with head movements and with the cues that triggered these head movements were prevalent. Frequently, the responses were directionally-specific (i.e., the magnitude or direction of change in firing rate of these neurons was substantially different for trials in which head movements were made to the left vs. the right). For some units, firing rates were altered only in response to the movement cue or only in association with head movements. However, the majority of neurons exhibited responses with both cue-related and movement-related components. Neuronal responses to the auditory cue usually were context-dependent, in that they did not occur if the same stimulus was presented when the animal was not performing the task. At least a small proportion of GP and NS neurons also appeared to exhibit context-dependent movement-related activity, in that responses occasionally were observed that were associated either with sensory-triggered head movements or with spontaneous head movements, but not with both. These data are consistent with previous suggestions that the activity of basal ganglia neurons during movement performance is highly dependent on the conditions associated with movement initiation. The data also indicate that the response characteristics of both GP and NS neurons in the rat are generally similar to those that have been described for basal ganglia neurons in primates and cats during sensory-triggered movement tasks. However, the proportion of task-related neurons that exhibited responses with both movement-related and cue-related components was greater than has generally been reported in studies of cats and primates, suggesting that neurons with these response properties may be more predominant in the rat basal ganglia.

Acoustic Stimulation↗

PubMed1992

Grafted neostriatal neurons express a late-developing transient potassium current.

Previous anatomical and physiological studies of neostriatal grafts have suggested that transplanted neurons do not develop beyond an early postnatal stage. We have tested whether this hypothesis can be generalized by characterizing the developmentally regulated Ca-independent potassium currents in graft neurons. These currents were studied using a combination of the whole-cell voltage-clamp technique with acutely-dissociated neurons and intracellular recording in slices. In all of the graft neurons examined with voltage-clamp techniques (n = 13), evidence was found for a slowly-inactivating potassium current that is seen only beyond the third or fourth postnatal week in normal rats. A current resembling the delayed rectifier was also seen in all sample neurons. The rapidly inactivating A-current which dominates recordings from nearly all immature neurons was seen in only about half (54%, 7/13) of the graft neurons; in a sample of normal adult striatal neurons, the A-current was detected in a similar percentage of neurons (41%, 25/62). Recordings of graft neurons in slices corroborated the voltage-clamp findings in revealing a slowly inactivating outward current that acts in the subthreshold potential range. These findings suggest that graft neurons express the normal complement of depolarization-activated potassium channel proteins seen in adult neurons.

Animals↗

PubMed1992

Presynaptic dopamine D1 receptors attenuate excitatory and inhibitory limbic inputs to the shell region of the rat nucleus accumbens studied in vitro.

1. Intracellular recordings were made from the shell region of the nucleus accumbens in an in vitro slice preparation. The mean resting membrane potential, input resistance, and action potential amplitude of these neurons were -76 +/- 1 mV, 87 +/- 5 M omega and 94 +/- 2 mV (N = 108), respectively. A sample of these neurons (N = 18) was identified as medium spiny neurons with the use of the biocytin-avidin labeling technique. 2. Electrical stimulation of the fornix, subcortical fibers, or neuropil within the nucleus accumbens shell itself elicited a depolarizing postsynaptic potential (PSP). Dopamine (10-100 microM) attenuated PSPs elicited by stimulation of all of these sites. In a paired-pulse stimulation protocol, dopamine was observed to enhance the facilitation of the test response with respect to the conditioning response. 3. The suppressive effect of dopamine was mimicked by the D1 receptor agonist SKF 82958 (10-30 microM), whereas the D2 receptor agonist quinpirole (10-30 microM) was ineffective. The action of dopamine was antagonized by the D1 receptor antagonist Sch 23390 (10-30 microM), but not by the D2 receptor antagonist sulpiride (10-50 microM) or various adrenergic receptor antagonists. 4. The PSP was usually composed of an excitatory postsynaptic potential (EPSP)-inhibitory postsynaptic potential (IPSP) sequence. Dopamine equally attenuated the excitatory and inhibitory component of the synaptic response. The attenuation of both EPSP and IPSP did not depend on membrane potential. 5. Dopamine effects on the resting membrane potential and input resistance were variable and did not correlate with changes in the PSP. Two further indications were found in favor of a presynaptic locus of dopaminergic modulation. First, the time course of the PSP was not altered during dopamine application. Second, dopamine did not attenuate depolarizations induced by bath-applied L-glutamate. In extracellular recordings, it was found that dopamine reduced the population spike but not the presynaptic fiber volley. 6. These findings strongly indicate that dopaminergic modulation of synaptic responses in neurons located in the accumbens shell region is mediated by presynaptic D1 receptors. Notably, dopamine does not exert a purely inhibitory effect on synaptic excitability in the nucleus accumbens, because it suppresses both the excitatory and inhibitory component of the synaptic response.

Afferent Pathways↗

PubMed1992

Intracellular analysis in vivo of different barosensitive bulbospinal neurons in the rat rostral ventrolateral medulla.

Neurons located in the rostral ventrolateral medulla (RVLM) with projections to the intermediolateral column (IML) in the spinal cord were electrophysiologically characterized and anatomically identified using an intracellular recording technique in vivo. A group of spontaneously active neurons was antidromically activated by electrical stimulation of the IML in the thoracic spinal cord (T2-T3 level). The axonal conduction velocities ranged from 1.5 m/sec to 11.0 m/sec; mean value, 5.5 +/- 2.6 m/sec (+/- SD). The firing pattern and changes in membrane potential in relation to the cardiac cycle were investigated in these bulbospinal neurons. A first group discharged action potentials with higher frequency at the end of the diastolic/beginning of the systolic period. The average of the neuronal membrane potentials demonstrated depolarizing potentials at the end of the diastolic/beginning of the systolic period. These depolarizing potentials increased in magnitude when the neurons were hyperpolarized. Therefore, they were characterized as EPSPs. The baroreceptor reflex activation produced by the increase in systemic arterial pressure following intravenous injection of phenylephrine elicited hyperpolarization, a decrease in the rate of discharge, and an increase in the membrane input resistance, suggesting that a disfacilitatory effect was produced by the activation of baroreceptor inputs on these bulbospinal neurons. Conversely, the inactivation of the baroreceptor reflex by intravenous injection of sodium nitroprusside produced depolarization and an increase in the firing rate. These neurons were characterized as baroreceptor-sensitive type I neurons. A second group of bulbospinal neuron in the RVLM was differentiated from the first group because it demonstrated a decrease in the frequency of discharge at the end of the diastolic/beginning of the systolic period. The average of the membrane potentials showed hyperpolarizing potentials that decreased in magnitude when the neuron was hyperpolarized. These hyperpolarizing potentials occurred at the end of the diastolic/beginning of the systolic period and were reversed in polarity after intracellular injections of chloride ions for several minutes. Therefore, these potentials were characterized as chloride-dependent IPSPs locked to the cardiac cycle. In some of these neurons, the electrical stimulation of the IML produced, in addition to the antidromic action potential, a monosynaptic EPSP with a shorter latency. Based on these unique characteristics, these neurons were defined as barosensitive type II neurons. During constant baroreceptor inactivation achieved by the hypotension produced by intravenous infusions of sodium nitroprusside, the pattern of discharge of barosensitive type II neurons became very regular, and the IPSPs locked to the cardiac cycle were absent.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1991

Intracellular study of rat globus pallidus neurons: membrane properties and responses to neostriatal, subthalamic and nigral stimulation.

Physiological properties of globus pallidus (GP) neurons were studied intracellularly in anesthetized rats. More than 70% of the neurons exhibited continuous repetitive firing of 2-40 Hz, while others exhibited periodic burst firing or no firing. The repetitively firing neurons exhibited the following properties: spike accommodation; spike frequency adaptation; continuous firing with a frequency of about 100 Hz generated by intracellular current injections; fast anomalous rectification; ramp-shaped depolarization upon injection of depolarizing current; and post-active hyperpolarization. The burst firing neurons evoked a large depolarization with multiple spikes in response to depolarizing current, and a similar response was observed after the termination of hyperpolarizing current. The few neurons which did not fire spontaneous spikes exhibited strong spike accommodation when they were stimulated by current injections. The continuously firing neurons were antidromically activated by stimulation of the neostriatum (Str) (23 of 68), the subthalamic nucleus (STh) (55 of 75), and the substantia nigra (SN) (25 of 46). The antidromic latencies of the 3 stimulus sites were very similar (about 1 ms). None of the burst firing neurons were antidromically activated. Three non-firing neurons evoked antidromic responses only after Str stimulation. Only repetitively firing neurons evoked postsynaptic responses following stimulation of the Str and the STh. Stimulation of the Str evoked initial small EPSPs with latencies of 2-4 ms and strong, short duration IPSPs with latencies of 2-12 ms. Stimulation of the STh evoked short latency EPSPs overlapped with IPSPs. Frequently, these responses induced by Str and STh stimulation were followed by other EPSPs lasting 50-100 ms. These results indicated: (1) that the GP contains at least 3 electrophysiologically different types of neurons; (2) that GP projections to the Str, the STh, and the SN are of short latency pathways; (3) that Str stimulation evokes short latency EPSPs followed by IPSPs and late EPSPs in GP neurons; and (4) that STh stimulation evokes short latency EPSPs overlapped with short latency IPSPs and late EPSPs in GP neurons.

Animals↗

PubMed1991

Double immunohistochemical detection of transmitter phenotype of proliferating cells using bromodeoxyuridine.

We describe a new method that can determine transmitter phenotype of proliferating nerve cells at a given age. The procedure is based on indirect sequential double antigen immunofluorescence histochemistry for transmitter-synthesizing enzymes (glutamic acid decarboxylase and tyrosine hydroxylase) and the thymidine analogue, bromodeoxyuridine. The method permits simple, rapid, and effective anatomical detection, and promises to reduce certain limitations inherent in a combination with tritiated thymidine autoradiography. Employing this technique, we observed that many striatal cells expressing gamma-aminobutyric acid (GABA) and nigral cells expressing dopamine undergo the final mitosis at embryonic days 13-14 in the rat.

Animals↗

PubMed1991

Intracellular study of rat entopeduncular nucleus neurons in an in vitro slice preparation: response to subthalamic stimulation.

Responses of rat entopeduncular nucleus (EP) neurons after stimulation of the subthalamic nucleus (STh) and the morphology of the EP neurons were studied using brain slice preparations. EP neurons were classified into two types based on their electrophysiological properties as reported previously. Of 87 EP neurons, 72 were Type I and the rest were Type II. Synaptic responses to STh stimulation were different in these two cell types. STh stimulation evoked excitatory postsynaptic potentials (EPSPs) followed by strong inhibitory postsynaptic potentials (IPSPs) in Type I neurons and EPSPs without strong IPSPs in Type II neurons. The EPSPs were considered to be monosynaptic because no large change in the latency (1.7 +/- 0.5 ms) resulted by alteration of stimulus intensity. The EPSPs were reversibly suppressed by kynurenic acid in a dose-dependent manner. Bath application of (+)-tubocurarine (10-50 microM) had no effect on EPSPs or IPSPs. Bath application of bicuculline methiodide (50-100 microM) markedly suppressed IPSPs evoked by STh stimulation and at the same time increased the amplitude and duration of EPSPs without affecting the latency. In the presence of bicuculline methiodide, EPSPs could induce plateau potentials and slow action potentials. Some type I and Type II neurons were intracellularly labeled by biocytin. Type I neurons were located throughout the EP but Type II neurons were located mainly in the dorsal portion of the EP. Medium sized somata of both Type I and Type II neurons were spine-free and fusiform or round in shape. They had 3-4 thick primary dendrites with diameters of 2-5 micron that branched into thin secondary dendrites.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMed1991

High- and low-voltage activated calcium currents are expressed by neurons cultured from embryonic rat neostriatum.

Current-clamp studies have shown that voltage-dependent Ca currents are present in rat neostriatal neurons. Although these studies have provided evidence for the presence of high-voltage activated Ca channels, it has been unclear whether low-voltage activated channels are also present. Using the whole-cell variant of the patch-clamp technique, we have studied isolated Ca currents in an attempt to answer this question. We have found that both high- and low-voltage activated calcium currents are expressed by neostriatal neurons cultured from embryonic rat brain. These currents are similar in voltage-dependence and pharmacology to those found in other brain neurons.

Animals↗

PubMed1991

Developmental regulation of a slowly-inactivating potassium conductance in rat neostriatal neurons.

In late embryonic and early post-natal rat neostriatal neurons, the voltage-dependent potassium currents activated by depolarization are largely attributable to a rapidly inactivating A-current and a delayed rectifier current. Over the first 4 weeks of post-natal life, a third potassium current emerges in most cells. This slowly inactivating conductance is distinct from the A-current and delayed rectifier in voltage-dependence, kinetics and pharmacology. The properties of this conductance suggest that it may be of central importance to the integrative behavior of neostriatal neurons by controlling such features as first spike latency and interspike interval.

Animals↗

PubMed1991

Inhibitory substantia nigra inputs to the pedunculopontine neurons.

Responses of 43 pedunculopontine area (PPN area) neurons to electrical stimulation of the substantia nigra (SN) were studied in anesthetized rats. An intracellular recording technique was used to demonstrate that SN stimulation evoked hyperpolarizing potentials, which were identified by intracellular injections as inhibitory postsynaptic potentials (IPSPs). These IPSPs were often followed by a rebound depolarization that originates several spike potentials. These IPSPs were characterized as monosynaptic, with latencies varying from 1.0 to 8.5 ms. Similar results were observed in some animals with chronic unilateral coronal lesion just rostral to subthalamic nucleus (STH), which severed the rostral afferents. PPN are neurons were also antidromically activated by SN stimulation. Two PPN area projection neurons were clearly identified. Mean latency of one group was 0.71 ms; mean latency of the second group was 5.16 ms. The morphological analysis of a neuron inhibited by SN stimulation and labeled with horseradish peroxidase (HRP) demonstrated that the soma was fusiform in shape, with the axon originating in the soma and collaterals and a large dendritic field extending in the ventrodorsalis direction. The results indicate that the PPN area is reciprocally connected with the SN, which elicits an inhibitory effect on PPN area neurons.

Animals↗

PubMed1991

Contribution of NMDA receptors to postsynaptic potentials and paired-pulse facilitation in identified neurons of the rat nucleus accumbens in vitro.

The principal aim of this study was to characterize the transmitter mechanisms mediating fast postsynaptic potentials in identified neurons of the rat nucleus accumbens. Using the biocytin-avidin labeling technique, impaled neurons were identified as medium spiny neurons. The basic membrane characteristics of these neurons were determined. Local electrical stimulation or stimulation of the corpus callosum elicited a depolarizing postsynaptic potential consisting of an EPSP often followed by an IPSP. The quisqualate/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (4 microM) abolished most of the depolarizing postsynaptic potential. The N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid depressed a small part of the decay phase of the depolarizing postsynaptic potential. Paired-pulse facilitation of postsynaptic potentials was found using interstimulus-intervals between 10 and 150 ms. N-methyl-D-aspartate receptors were found to contribute only slightly to the facilitation of the decay phase of the depolarizing postsynaptic potential, but not to its rising phase. This contribution was particularly clear under conditions of reduced GABAA receptor mediated inhibition. The present study indicates that postsynaptic responses of medium spiny neurons in the nucleus accumbens to local stimulation or stimulation of neocortical afferents are primarily mediated by quisqualate/kainate receptors. The contribution of NMDA receptors is normally limited to a portion of the decay phase of these responses, but is enlarged in the absence of GABAergic inhibition and following paired-pulse stimulation.

2-Amino-5-phosphonovalerate↗

PubMed1991

Hippocampal inputs to identified neurons in an in vitro slice preparation of the rat nucleus accumbens: evidence for feed-forward inhibition.

The aim of the present study was to analyze responses of nucleus accumbens neurons to stimulation of the fornix. The recorded neurons were labeled with biocytin and identified as medium spiny neurons. A large majority of cells generated a depolarizing postsynaptic potential in response to stimulation of the fornix. Using intracellular current injection, this depolarizing response was dissociated into an EPSP reversing at -6 +/- 6 mV and an IPSP reversing at -71 +/- 4 mV. Both the EPSP and IPSP were abolished by 6-cyano-7-nitroquinoxaline-2,3-dione. In addition, the IPSP was blocked by bicuculline and picrotoxin. The onset latency of the EPSP was constant in spite of varying stimulus intensities. In contrast, the onset latency of the IPSP increased with decreasing stimulus intensity. Notably, the stimulus threshold for evoking IPSPs was generally lower than for EPSPs. At stimulus intensities well above threshold, the IPSP onset was only slightly delayed with respect to the EPSP onset. These results indicate that the EPSP can be characterized as a monosynaptic and glutamate-mediated synaptic response. The IPSP, however, appears to be mediated by a disynaptic feed-forward pathway involving both glutamate and GABAA receptors. Recurrent and lateral inhibitory interactions have previously been proposed to be predominant organizational principles in the caudate-putamen and nucleus accumbens. This study indicates that feed-forward inhibition is an additional principle governing the activities of striatal neural networks.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1990

Electrophysiological properties of pedunculopontine neurons and their postsynaptic responses following stimulation of substantia nigra reticulata.

Membrane properties and postsynaptic responses to stimulation of the substantia nigra reticulata (SNr) of the neurons in rat pedunculopontine nucleus (PPN) were studied in an in vitro parasagittal slice preparation using intracellular recording techniques. Based on electrical membrane properties, PPN neurons were classified into 3 types (types I, II and II). The unique feature of the type I neuron was the low threshold calcium spike while the type II neuron had various inward and outward rectifications. The type III neuron showed no such features as those observed in type I or II neurons. Some recorded neurons were intracellularly labeled with biocytin to study their morphology, and their transmitter phenotype was investigated by immunocytochemistry for choline acetyltransferase (ChAT). The type I and III neurons were found to be non-cholinergic, but 50% of the labeled type II neurons were immunopositive for ChAT. Morphological features of type II neurons were also different from type I or III neurons. The soma of the type II neuron was almost always more than twice as large as that of type I and III neurons. Inhibitory postsynaptic potentials (IPSPs) were induced in all 3 types of PPN neurons following stimulation of SNr. SNr-induced IPSPs were usually followed by a slow depolarizing potential from which rebound spikes were triggered. These rebound excitations were found only in type I and II neurons. These data indicate that heterogeneous groups of neurons exist in the PPN in terms of morphology, transmitter phenotypes and electrical membrane properties.

Action Potentials↗

PubMed1990

Muscarinic regulation of cyclic AMP metabolism in rat neostriatal cultures.

Muscarinic receptor expression and function were investigated in cultured rat neostriatum. Muscarinic receptor levels were determined from saturation binding experiments performed on intact cultures using [3]N-methylscopolamine. In cultures maintained for 3, 7 and 12-14 days in vitro, the Bmax was 2.3, 5.4 and 10.9 fmol/culture. The average number of receptors per neuron increased during the 2nd week in vitro. Carbachol (100 microM) had no significant effect on basal cAMP levels but reduced cAMP levels elevated by forskolin. Carbachol significantly reduced cAMP levels stimulated with dopamine only in cultures untreated with a phosphodiesterase inhibitor. Comparing equimolar doses, the carbachol response was more sensitive to the M1 selective antagonist pirenzepine than the cardioselective M2 antagonist AF-DX 116. These results suggest that the muscarinic receptors regulate cAMP levels in neostriatal neurons and, in so doing, provide a post-synaptic substrate for the interaction of dopamine and acetylcholine.

1-Methyl-3-isobutylxanthine↗

PubMed1990

Serotonin enhances excitability in neostriatal neurons by reducing voltage-dependent potassium currents.

The physiological effects of serotonin (5-HT) on rat neostriatal neurons were investigated using current-clamp techniques in neostriatal slices and voltage-clamp techniques in acutely dissociated adult neostriatal neurons. In most neurons (35/51), bath-applied 5-HT (10-60 microM) decreased the first spike latency and increased the evoked firing frequency. Membrane input resistance was also increased in most neurons (33/35) but could not explain the enhanced responsiveness. Tetrodotoxin, at concentrations sufficient to block spike production, did not block the ability of 5-HT to enhance the slow ramp-like voltage trajectory produced by depolarizing current injection. The role of potassium currents in the 5-HT effect was examined using whole cell voltage-clamp; in 6 of 9 neurons, 5-HT reversibly decreased inactivating potassium currents activated by depolarization. These experiments suggest that 5-HT's effect on the ramp trajectory may be mediated by a reduction of potassium currents activated by sub-threshold depolarization.

Animals↗

PubMed1990

Intracellular study of rat entopeduncular nucleus neurons in an in vitro slice preparation: electrical membrane properties.

Electrical properties of rat entopeduncular nucleus (EP) neurons were studied in vitro using slice preparations. Of 108 EP neurons recorded, 104 were classified into two types based on their membrane properties. Type I neurons (n = 86) possessed: (1) a strong, time-dependent anomalous rectification that was sensitive to Cs+; (2) a weak spike adaptation; and (3) a strong rebound excitation with a low threshold Ca-spike and fast spikes. Many Type I neurons displayed spontaneous repetitive firing. Some of them generated spontaneous Ca-dependent plateau potentials with fast spikes upon application of tetraethylammonium bromide. Type II neurons (n = 18) had: (1) no apparent rectification; (2) a strong spike adaptation; and (3) a ramp-shaped repolarization, similar to the A-current, at the offset of a hyperpolarizing pulse. Features common to both types included: (1) a similar range of the input resistance; (2) capability of generating high threshold Ca-spikes; and (3) generation of postactive hyperpolarizations (i.e. Ca-activated K-conductance). The great majority (Type I) of rat EP neurons share similar electrical properties. A minority of neurons (Type II) behave differently from Type I neurons and share similar properties among themselves.

Action Potentials↗