摘要:

AbstractExperiments were done at the neuromuscular junctions (NMJs) of the cutaneous pectoris muscle of the frog to test the validity of the “spatial decay method” which uses simultaneous recording with two intracellular electrodes, each located in the muscle fiber near a distal end of the terminal. The miniature endplate potential (MEPP) peak amplitude recorded by each electrode is used to calculate the position of the release site producing it as well as its initial amplitude in front of its release site. The validity of the method was tested with a third focal electrode located between the two intracellular electrodes, at about 60–100 μm from one of the intracellular electrodes. the probability of spontaneous transmitter release was not uniform along the NMJ either in low or in normal Ca2+ +concentration. The release sites located in the region close to the first point of contact between the axon and the muscle fibre, usually close to the center of the NMJ, were spontaneously more active than the distal release sites. The degree of the steepness of proximodistal release gradients varied among different junctions. The less active regions tended to produce smaller MEPPs than did the more active ones. In fact, a correlation was found between the logarithm of MEPP frequency in a given region and the mean corrected MEPP amplitude in that region. These results also show that MEPP frequency was modulated to a greater extent than MEPP amplitude along the frog nerve terminal. The proximodistal gradient in MEPP frequency may be related to corresponding gradients in density and length of release sites along the junction, whereas MEPP amplitude gradients may be related to gradients in the length of release sites and/or postjunctional

ISSN:0887-4476    

DOI:10.1002/syn.890030402

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe effects of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) administration on whole brain dopamine content and monoamine oxidase subtype B (MAO‐B) activity were assessed in Swiss‐Webster male mice. Groups of mice at six different ages (1,2,4,8,16, and 52 weeks) were treated with either MPTP(12.5 mg/kg) every 2 hours for four subcutaneous injections or with the saline vehicle in the same injection volume. A third group of subjects was untreated and sacrificed at the same ages. The animals were sacrificed 1 week following treatment. The brains were removed and divided into right and left halves. The right brain halves from all subjects of a given age were assayed for MAO‐B activity. The left brain halves were assayed for dopamine content using high performance liquid chromatography.The results revealed a significant age‐dependent increase in both dopamine content and MAO‐B activity in the untreated controls. It was also found that the toxic effect of MPTP as measured by whole brain dopamine depletion was increased at each successive age tested. There was a significant correlation (r = + 0.96) between the baseline levels of MAO‐B activity and the degree of lesion induced by MPTP treatment. These results indicate that the increased sensitivity to MPTP reported in aged animals may, in part, be attributable to the increase in MAO‐B ac

ISSN:0887-4476    

DOI:10.1002/syn.890030403

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

年代:1989

数据来源: WILEY

摘要:

AbstractPreparations of acetylcholine receptor‐rich (AChR‐rich) postsynaptic membranes from electric tissue of electric rays often contain an Mr55,000 protein (55kD protein) that has not been previously characterized. Using a monoclonal antibody (MAb 1403) against the 55kD protein fromTorpedo californicaand a pan‐specific, anti‐intermediate filament antibody (Pruss et al., 1981; Cell 27:419–428), we show that the 55kD protein has the properties expected of Torpedo desmin. By the electron microscope immunogold method applied to perfusion‐fixed electric tissue, MAb 1403 labeled only cytoplasmic filaments in the electroplax. These filaments were neither more concentrated nor arranged detectably differently in postsynaptic regions relative to nonpostsynaptic regions. The 55kD protein could also be fractionated away from isolated postsynaptic membranes by gradient centrifugation. The protein is thus a minor component of the postsynaptic membrane in situ and after isolation. On semithin cryosections of rat skeletal muscle, on the other hand, MAb 1403, which recognizes rat desmin but not rat vimentin, gave strong fluorescent labeling of the postsynaptic region, weaker labeling of the Z‐line, and still weaker labeling of the cell surface immediately surrounding extrajunctional nuclei. The pattern of postsynaptic labeling suggests that desmin, presumably in the form of intermediate filaments, occurs near the AChR‐rich crests of the junctional folds, but is particularly concentrated among and around the ends of the folds. Similar results were obtained with a second monoclonal antibody raised against authentic desmin. These results suggest that desmin intermediate filaments may have an important role in organization of the postsynaptic cytoplas

ISSN:0887-4476    

DOI:10.1002/syn.890030404

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

年代:1989

数据来源: WILEY

摘要:

AbstractRadioligand binding studies were performed to characterize serotonin 5HT1Dbinding sites in porcine and bovine brain. 3H‐5HT binding, in the presence of 1 μM (+/−)pindolol (to block 5HT1Aand 5HT1Breceptors) and 100 nM mesulergine (to block 5HT1creceptors), was specific, saturable, and of high affinity. In porcine and bovine cortex and striatum the majority of 5HT1sites (80%‐90%) were of the 5HT1Dsubtype. In competition experiments 8‐OH‐DPAT, TFMPP, mesulergine, DOB, and ICS 205‐930 had low affinity for 3H‐5HT‐labeled 5HT1Dsites, indicating that the pharmacology of the 5HT1Dsite is distinct from previously identified 5HT1A, 5HT1B, 5HT1C, 5HT2, and 5HT3sites. Guanyl nucleotides, GTPgammaS, and Gpp(NH)p, and divalent cations potently modulated the binding of 3H‐5HT to 5HT1Dsites in porcine and bovine striatum. Mg+ +ions increased the number and affinity of 3H‐5HT‐labeled 5HT1Dsites, while guanyl nucleotides decreased the number of 3H‐5HT‐labeled 5HT1Dsites. These results demonstrate the presence of the 5HT1Dreceptors in porcine striatum and bovine cortex and provide direct demonstration that the radioligand binding assay for the 5HT1Dreceptor can monitor the interaction of this receptor

ISSN:0887-4476    

DOI:10.1002/syn.890030405

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

年代:1989

数据来源: WILEY

摘要:

AbstractIn general, it has been difficult to preserve electrophysiologically viable motoneurons in brain slices from adult mammals. The present study describes a new method for obtaining viable motoneurons in the facial nucleus of adult rat brain slices. The essence of the method was to use a modified artificial cerebrospinal fluid (ACSF) in which NaCl was replaced initially by sucrose; the modified ACSF was used during (1) slice preparation and (2) a 1 hr recovery period. The rationale for the modification is discussed in terms of the proposed acute neurotoxic effects of passive chloride entry and subsequent cell swelling and lysis. The actual recordings were made only after switching back to normal ACSF. Use of this method yielded large numbers of viable motoneurons that were suitable for intracellular recording; no motoneurons survived when normal ACSF (i.e., with NaCl) was used during slice preparation. A survey of some electrophysiological and pharmacological properties of facial motoneurons in this preparation, by means of current‐clamp and voltage‐clamp recording, revealed close similarities to the properties of adult motoneurons previously observed in vivo (e.g., time‐dependent inward rectification, apamin‐sensitive afterhyperpolarization, and serotonin‐induced slow depola

ISSN:0887-4476    

DOI:10.1002/syn.890030406

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

年代:1989

数据来源: WILEY

摘要:

AbstractNigrostriatal dopamine (NSDA) neurons have been hypothesized to play an important regulatory role in neostriatal sensorimotor integration. In order to provide further information on the nature of sensory modulation of NSDA cells, we have examined the pharmacology of the responsiveness of these neurons to peripheral nerve stimulation. The selective D1 dopamine receptor agonist SKF 38393 enhanced the normal inhibition of NSDA neurons produced by electrical stimulation of the sciatic nerve. The SKF 38393‐induced enhancement, but not the basal stimulation‐induced inhibition itself, was blocked by prior hemitransection of the forebrain and was reversed by the selective D1 antagonist SCH 23390 but not by the selective D2 antagonist 1‐sulpiride. SCH 23390 alone, however, exerted no effect on this inhibition. The selective D1 receptor agonist fenoldopam, which does not cross the blood‐brain barrier, also failed to alter the response to sciatic nerve stimulation (i.v. administration). Thus, central D1 receptors (rostral to the midbrain) appear to be involved in a system which mediates phasic control over sensory modulation of NSDA neuronal a

ISSN:0887-4476    

DOI:10.1002/syn.890030407

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

年代:1989

数据来源: WILEY

摘要:

AbstractCholecystokinin, (CCK) 1‐400 ng, significantly potentiated the hypolocomotion induced by dopamine, when simultaneously microinjected bilaterally into the ventral tegmental area (VTA) of rat brain. Within this dose range, CCK had no effect alone on ambulatory locomotion. Topographical analysis indicated that the modulatory effect of CCK was greatest in the central and caudal regions of the VTA, and absent at sites lateral, dorsal, rostral, and caudal to the VTA. Pharmacological analysis indicated that both unsulfated CCK octapeptide (100 ng) and the C‐terminal tetrapeptide of CCK (400 ng) potentiated dopamine‐induced hypolocomotion in a manner identical with sulfated CCK octapeptide (100 ng). Proglumide, an antagonist of the peripheral‐type CCK receptor, did not block the potentiating actions of CCK, at doses of proglumide up to 500 mg/kg i.p., or 100ng into the ventral tegmental area. L‐364,718, an antagonist of the peripheral‐type CCK receptor with lesser affinity for the central‐type CCK receptor, blocked the potentiating actions of CCK at relatively high doses of L‐364,718 (1‐10 mg/kg i.p.). These findings suggest that CCK acts as a facilitatory modulator of dopamine at a central‐type CCK receptor on

ISSN:0887-4476    

DOI:10.1002/syn.890030408

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

年代:1989

数据来源: WILEY

摘要:

AbstractCalcium/calmodulin‐dependent protein kinase type II, a multimeric 550‐650 kilodalton enzyme composed of major alpha (50 kilodalton) and beta/beta' (60/58 kilodalton) subunits, is present in high concentrations in mammalian brain. Previous immunocytochemical studies indicated that the enzyme is enriched in cell bodies and dendrites, but did not show a clear‐cut localization in nerve terminals. The present study present evidence, using lesion‐induced degenerations of pre‐ and postsynaptic neuronal populations in the neostriatum and substantia nigra, that calcium/calmodulin‐dependent protein kinase II, as measured both by autophosphorylation of enzyme subunits and by synapsin I kinase activity, is present in high concentrations in several populations of presynaptic terminals. Lesions of the corticostriatal tract decreased the amount of enzyme by 30‐40% in the neostriatum, a decrease similar to that seen in the same region of synapsin I, a general nerve terminal market. Lesions of the striatonigral tract induced an even more pronounced decrease of the enzyme in the substantia nigra; this decrease was larger than the lesion‐induced change of synapsin I seen in the same region. Our data therefore indicate that certain nerve terminal population in the rat brain contain high levels of calcium/calmodulin‐dependent

ISSN:0887-4476    

DOI:10.1002/syn.890030409

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

年代:1989

数据来源: WILEY

摘要:

AbstractLarge striatal neurons are spared in caudate tissue from postmortem brain of patients with Huntington's disease (HD) and in the rat caudate lesioned with excitotoxins at short postlesion intervals. In order to determine the survival of large neurons and other effects of excitotoxicity at longer postlesion intervals the rat caudate nucleus was examined 2,7, and 30 weeks after intrastriatal injections of the excitotoxin, quinolinic acid. The caudate nucleus diminished in size progressively up to 30 weeks postlesion due to (1) shrinkage and compacting of the lesion zone and (2) reduction in area of intact caudate, apparently due to gradual loss of the remaining caudate neurons.In Nissl‐stained sections of the lesion zone where total neuronal density was less than 5% of contralateral control, large neurons were present at all postlesion intervals, forming 38‐58% of the remaining neurons. Unexpectedly, a fivefold reduction in the number of large neurons was observed between 2 and 30 weeks postlesion. Also, at 7 and 30 weeks postlesion most of the large neurons were confined to the peripheral region of the lesion. At all postlesion intervals, large neurons retained ultrastructural integrity and some synaptic inputs despite the severe disruption of the surrounding neuropil.Surrounding the lesion zone was a transition zone which exhibited a decrease in total neuronal density to 53‐74% of control. In this region the density of large neurons was not diminished, and the proportion of large neurons was elevated in comparison to that of controls at all postlesion intervals.Findings suggest that following excitotoxic lesion of the caudate nucleus there are marked differences between short‐ and long‐term postlesion intervals in the survival and distribution of large neurons. We speculate that an imbalance in the synaptic connections with other caudate neurons leads to the persistent loss of large neurons in the lesion zone at long postlesion intervals. A transition zone surrounding the lesion, where cell loss is less severe than in the lesion zone, exhibits features more characteristic of the neuropathol

ISSN:0887-4476    

DOI:10.1002/syn.890030410

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

年代:1989

数据来源: WILEY

摘要:

Abstract3H‐GBR 12935 was used to label the digitonin‐solubilized dopamine transporter from dog caudate nucleus. Specific binding to soluble fractions was observed in dog caudate but was absent in rat cerebellum. Binding to the solubilized transporter sites was saturable and of high affinity (Bmax= 2.57 ± 0.60 pmol/mg protein, KD= 23.42 ± 2.24 nM, n = 4). Heating or addition of trypsin abolished specific binding in the soluble fractions. In competition studies, soluble3H‐GBR 12935 binding was inhibited by mazindol, GBR 12909, nomifensine, dimethocaine, dopamine, (−) cocaine, and (+) cocaine in a manner typical of binding to the dopamine transporter. As expected, tomoxetine and citalopram, inhibitors of norepinephrine and serotonin uptake, respectively, were weak competitors of3H‐GBR 12

ISSN:0887-4476    

DOI:10.1002/syn.890030411

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

年代:1989

数据来源: WILEY