摘要:

AbstractThe electrophysiological characteristics of two subtypes of striatal neurons, identified by their distinct patterns of response to paired impulse stimulation of corticostriatal afferents, were compared using in vivo intracellular recordings in rats. As observed in previous extracellular recording studies, the majority of neurons (73%) were found to be of the Type II class, with the remaining cells exhibiting the Type I response patern. For all cells, cortical stimulation elicited 5–30 mV EPSPs at latencies ranging from 2.0–5.3 msec; Increasing the stimulating current intensity caused a progressive increase in the amplitude of the evoked EPSPs without altering their latencies, suggesting that the EPSPs are monosynaptically mediated. Both the average amplitude and duration of the evoked EPSPs at spike threshold in Type I neurons (9.8 ± 1.7 mV, 11.8 ± 2.8 msec; mean ± SEM) were significantly smaller than those of Type II cells (20.3 ± 1.4 mV, 22.7 ± 2.1 msec). Although the average latency to the onset of the EPSP was similar for both cell classes (Type I cells: 2.3 ± 0.3 msec; Type II cells: 2.2 ± 0.2 msec), the EPSPs in Type I cells reached peak amplitude and the spikes were triggered at significantly longer latencies than in the Type II cells (peak I: 11.2 ± 2.5 msec vs. II: 7.6 ± 0.7 msec; spike I: 8.0 ± 1.2 msec vs. II: 5.7 ± 0.4 msec).Striatal neurons had a comparatively hyperpolarized resting membrane potential (−70.2 ± 2.1 mV) and had an average input resistance of 35.4 ± 7.6 MΩ. Overall, striatal neurons exhibited low levels of spontaneous activity (0.6 ± 0.7 Hz) with 50% of the neurons being quiescent. Type I cells exhibited significantly higher firing rates (3.2 ± 0.8 Hz) than Type II cells (0.8 ± 0.3 Hz), although their resting membrane potentials were not significantly different. Spontaneously occurring spikes had an average amplitude of 72.7 ± 3.4 mV and spike thresholds of −50.1 ± 1.5 mV. Irregularly occurring depolarizing plateau potentials, which typically gave rise to spike discharge, were frequently observed in both spontaneously firing and quiescent neurons. A small proportion of the cells recorded (3/55) exhibited a Type I response pattern but had unique physiological characteristics that were similar to those described by others as arising from large, aspiny striatal neurons.The present study shows that these two physiologically distinct neuron types appear to be similar in terms of their passive membrane properties (e.g., resting membrane potentials, input resistance, etc.) and firing characteristics, despite their unique patterns of response to corticostriatal stimulation. Therefore, the source of the distinct paired impulse response profiles of these neurons is more likely to arise from differences in their afferent drive than from a heterogeneity in their membrane properti

ISSN:0887-4476    

DOI:10.1002/syn.890160302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractBuprenorphine is a synthetic opioid proposed as a potential treatment for drug abuse. Although buprenorphine is widely considered to be a partial agonist at opioid receptors, little is known of its electrophysiological effects in the central nervous system. Because buprenorphine has been reported to have limited hedonic effects in humans, and since activation of the dopaminergic system is thought to be critical to the reinforcing effects of drugs, we compared the ability of buprenorphine and morphine to activate dopamine neurons. We report here that buprenorphine and morphine are equally effective in increasing the impulse flow of dopamine cells in the ventral tegmental area.Extracellular single unit activity was recorded from dopaminergic (DA) neurons in the ventral tegmental area (VTA) of chloral hydrate anethestized rats. Standard physiological and anatomical criteria were used to identify DA neurons. Systemic injection of buprenorphine (5–200 μg/kg, i.v.) and morphine (1–10 mg/kg, i.v.) produced equal magnitudes of activation in a similar subset of DA neurons in the VTA (buprenorphine: 173%; morphine: 164%). Unlike morphine, the activation by buprenorphine was not reversed by the opioid antagonist naloxone (50–100 μg/kg, i.v.), but this is consistent with the known pharmacodynamics of buprenorphine at opioid receptors.These studies demonstrate that acute administration of buprenorphine has morphinelike effects on the impulse activity of DA neurons. The implications for use of buprenorphine as a clinical treatment for drug abuse are discussed. © 1994 Wiley

ISSN:0887-4476    

DOI:10.1002/syn.890160303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractMercuric chloride was found to have a biphasic effect on the binding of the radiolabeled stimulant [3H]methylphenidate to membranes from a crude synaptosomal preparation of rat striatal tissue. Binding was enhanced at low concentrations of HgCl2, reaching a maximum of 62% above control values at 2.5 μ HgCl2. It was inhibited in a dose‐dependent manner at concentrations greater than 5 μ HgC12, with an IC50of 7.2 μ. The increase in binding observed at the low concentrations of HgC12was shown by Scatchard analysis to be due to an increase in the affinity of [3H]methylphenidate for its binding site on the dopamine transporter, while a decrease in both affinity and Bmaxaccompanied the reduction of [3H]methylphenidate binding observed at the higher concentrations of the inorganic mercury compound. The sodium salt of the organic mercurialp‐chloromercuriphenylsulfonic acid also caused an increase in [3H]methylphenidate binding (159% above controls at 2,000 μ), followed by an immediate decrease in binding at higher concentrations of the reagent. Because both of these mercury‐containing compounds have a high propensity for interacting with sulfhydryl groups, these data suggest that the cysteine residues in the dopamine transporter molecule may play an important role in the regulation of stimulant binding to the uptake complex. © 1994 Wiley

ISSN:0887-4476    

DOI:10.1002/syn.890160304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractTwo subtypes of neurons in the striatum have been defined on the basis of their different response patterns to paired‐impulse stimulation of corticostriatal afferents, with type I cells showing a longer spike latency, facilitation at short intervals, and inhibition at long intervals, and type II cells defined by the facilitation occurring at long interstimulus intervals. Nevertheless, the companion report has shown that this distinction of cell types cannot be accounted for by differences in the basic physiological properties of these cells, but instead is likely to be due to differences in their synaptic connectivity. The experiments performed in this study were directed at examining in detail the membrane factors and synaptic responses that may contribute to these distinct response patterns.When pairs of stimuli were delivered to the corticostriatal fibers at 10‐30 ms interstimulus intervals, the EPSPs elicited in type I neurons exhibited a temporal summation, resulting in a facilitation of spike firing to the second stimulus relative to the first. In contrast, type II cells showed decreased EPSP amplitude at short intervals, and in cells showing a short‐interval inhibition, there was a significant increase in spike threshold (+5.3 ± 1.4 mV) during the second response. All type II neurons recorded with KCl‐filled microelectrodes showed short‐interval facilitation with little or no change in spike threshold. Although the use of KCI electrodes did not alter the facilitation at short intervals in type I neurons it did increase the rate of rise of the EPSP, causing spikes to be triggered at a latency similar to that of type II cells.Paired stimuli delivered at 75–150 ms interstimulus intervals showed inverse effects on type I and type II cells with respect to the probability of spike firing. In type I cells, the evoked EPSP was followed by a long‐latency membrane hyperpolarization that prevented the second EPSP from reaching spike threshold. In contrast, the smaller‐amplitude hyperpolarization evoked in type II cells enabled the second stimulus to activate an EPSP at the same membrane potential as the first stimulus, resulting in a facilitation of spiking.Therefore, despite the similarity in the basic physiological properties of type I and type II cells, the differences in their spike latencies and paired impulse response profiles appear to be dependent on the timing of their GABAergic inhibition at short intervals: A GABA‐mediated conductance change occurs simultaneously with the EPSP in type I cells leading to a delay in triggering the evoked spike, whereas a later‐developing GABA conductance change in type II cells results in an inhibition of spiking at short intervals. In contrast, the pronounced long‐duration membrane hyperpolarization of type I cells appears to underlie the inhibition of spiking at long intervals, whereas in the type II cells the GABA‐mediated decrease in cell excitability necessitated the use of larger‐amplitude stimulation pulses to reach threshold with respect to the first stimulus, resulting in a higher probability of spike discharge to the second stimulus at long interva

ISSN:0887-4476    

DOI:10.1002/syn.890160305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractBrain microdialysis was used to determine whether systemic or local application of choline would modify the extracellular concentration of acetylcholine (ACh) in the nucleus accumbens (NAc) of freely moving rats. Supplemental choline given intraperitoneally or into the NAc of normal rats did not increase extracellular ACh. When local ACh interneurons in the NAc were treated pharmacologically to deplete the intracellular stores of ACh, then systemic choline (80 mg/kg) was an effective treatment. Specifically, )1) blockade of the high‐affinity choline transporter with hemicholinium‐3 (HC‐3) to reduce ACh synthesis caused a decrease in extracellular ACh, but choline supplementation restored ACh toward its normal level in the NAc. (2) Local bicuculline treatment released ACh to the point of depletion, but systemic choline or locally infused choline helped maintain normal ACh levels. These results suggest that choline supplementation might be useful in preventing depletion of ACh in the nucleus accumbens during pathological conditions. © 1994 Wiley‐L

ISSN:0887-4476    

DOI:10.1002/syn.890160306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractKynurenic acid (KYNA), an endogenous antagónist of ionotropic excitatory amino acid (EAA) receptors, was tested for its ability to modulate N‐methyl‐D‐aspartate (NMDA)‐ and α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA)induced excitation of dopamine (DA)‐containing neurons in the zona compacta of the rat substantia nigra (SNc). Experiments were conducted using extracellular recording techniques in conjunction with an in vitro brain slice preparation. Bath application of NMDA (1–20 μ) or AMPA (0.5–10 μ) produced a concentration‐dependent increase in the firing rate of SNc DA neurons but had no effect on firing pattern. The highest concentration of both agonists produced a rapid and reversible cessation of activity that was attributed to acute induction of depolarization block. Addition of glycino (GLY) (up to 100 μ) to the bathing solution had no effect on either basal firing rate or the increase in activity produced by NMDA. KYNA (10 μ–1 mM) antagonized the excitatory effects of both NMDA (15 μ) and AMPA (3 μ) in a concentration‐dependent fashion (IC50: 102 μ and 64 μ, respectively) without affecting basal firing rate. Perfusion of tissue slices with a modified Ringer's solution containing low Mg2+(0.12 mM) increased NMDA‐induced excitation but did not affect the antagonist properties of KYNA. D‐serine (100 μ) reversed the ability of KYNA to block the excitatory effects of NMDA, suggesting that KYNA attenuates NMDA‐induced excitation of SNc DA neurons via blockade of the GLY allosteric site on the; NMDA receptor. The ability of KYNA to modulate the excitatory effects of both NMDA and non‐NMDA agonists implies that endogenous KYNA may play a physiological role it reg

ISSN:0887-4476    

DOI:10.1002/syn.890160307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractIn the first two reports of this series, in vivo intracellular recording techniques were used to characterize the electrophysiological properties of two types of striatal neurons that had been identified by their distinct response patterns to stimulation of corticostriatal afferents. In this paper, we examined whether cells showing Type I or Type II response patterns also differed with respect to their morphology or compartmental localization by combining intracellular recording and Lucifer yellow staining with immunocytochemical localization of calbindin 28 kd immunoreactivity.In the majority of cases, both Type I and Type II neurons exhibited similar morphological characteristics, with 80% of the Type I cells (13/16) and all of the Type II cells (n = 40) being small or medium spiny neurons. In each case where the morphological class of the cell was different than the spiny cell class, the cell exhibited a Type I response pattern. These spiny neurons had somata that averaged 17.1 ± 1.3 μm in diameter and gave rise to between four and eight primary dendrites. The axons typically arose from cell bodies (7/13 for Type I and 25/40 for Type II cells) and emitted extensive local axonal collaterals. However, the axons of Type I cells more frequently originated from the dorsal surface of the somata (9/13; 69%), whereas Type II axons more frequently arose from the ventral surface of the somata (25/35; 71%), which may account for their different extracellular waveforms. In coronally sectioned tissue (n = 18), the axons always projected laterally when the somata were located in the medial striatum and projected medially when the somata were in the lateral striatal region.In a subset of experiments (N = 22), Lucifer yellow‐stained neurons were localized with respect to their position within the patch and matrix compartments of the striatum using subsequent staining for calbindin 28 kd immunoreactivity. Of the 20 labeled medium spiny neurons examined (Type II: N = 13; Type I: N = 7), 19 were located in the calbindin‐positive matrix compartment. The only neuron localized to the patch compartment was a medium spiny cell that exhibited a Type II paired impulse response pattern. In addition, of the two aspiny neurons from this group with beaded dendrites, one was localized to the border between adjacent patch and matrix compartments, whereas the other was located completely within the matrix compartment. Therefore, despite their distinct paired impulse response patterns, the majority of both Type I and Type II neurons were medium spiny cells located in the matrix compartment of the striatum.This series of studies shows that corticostriatal pathway stimulation can be used effectively to distinguish between two morphologically and physiologically similar types of medium spiny neuron in the striatum. Furthermore, evidence is consistent with a model wherein these two cell types represent the sites of origin of the two parallel efferent systems emanating from the striatum. © 1994 Wiley‐L

ISSN:0887-4476    

DOI:10.1002/syn.890160308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890160301

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY