摘要:

AbstractSubstitution of the chlorine atom by a radio‐iodine in position 5 in the zacopride molecule yielded [125I]iodo‐zacopride that bound with high affinity (Kd= 4.3 nM) to 5‐HT3receptors in the rat central nervous system. Assays with membranes from the posterior (mainly entorhinal) cortex confirmed that the pharmacolgical properties and regional distribution of [125I]iodo‐zacopride‐specific binding sites were identical with those of 5‐HT3sites labelled by the reference radioligand [3H]zacopride. Autoradiographic investigations for the visualization and quantification of 5‐HT3receptors yielded similar results with both radioligands, but autoradiograms could be obtained after only 1–3 days of exposure of sections labelled with [125I]iodo‐zacopride, instead of 4–6 months using [3H]zacopride. The highest density of 5‐HT3sites was found in the nucleus tractus solitarius followed by, in decreasing order, the dorsal motor nucleus of the vagus nerve, the superficial layers of the dorsal horn in the spinal cord, the nucleus of the spinal tract of the trigeminal nerve, and the area postrema. Significant labelling of 5‐HT3receptors was also observed in limbic areas (amygdala, hippocampus, frontal and entorhinal cortex), and to a much lower extent in the dorsal raphe nucleus, striatum, and substantia nigra. These multiple locations further support the idea that 5‐HT3receptors are probably involved in several 5‐HT‐mediated functions

ISSN:0887-4476    

DOI:10.1002/syn.890100402

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe aim of the present study was to identify cellular elements bearing high‐affinity neurotensin (NT) binding sites in the suprachiasmatic nucleus (SCN) of the rat hypothalamus. Because the distribution of these binding sites had previously been reported to conform to that of both vasoactive intestinal peptide (VIP)‐containing nerve cell bodies and serotonin (5‐HT)‐containing axons, the following experimental approaches were used: (1) the overlap between autoradiographically labeled NT binding sites and immunocytochemically labeled VIP neurons was examined in adjacent 5‐μmthick sections taken across the entire rostrocaudal extent of the SCN; and (2) the density of NT binding sites was examined by quantitative autoradiography following cytotoxic lesioning of 5‐HT afferents. Double‐labeling studies demonstrated precise overlap between125I‐NT binding and VIP immunostaining throughout the SCN. Moreover, at high magnification intensely VIP‐immunoreactive neurons were found in direct register with125I‐NT‐labeled cells visualized in adjacent sections. Densitometric autoradiographic studies demonstrated a significant reduction in specific125I‐NT binding within the SCN following intracerebroventricular injection of the neurotoxin, 5,7‐dihydroxytryptamine. Taken together, these results indicate that within the SCN, NT receptors are present both presynaptically on serotonin axons and postsynaptically on the perikarya and dendrites

ISSN:0887-4476    

DOI:10.1002/syn.890100403

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

年代:1992

数据来源: WILEY

摘要:

AbstractTo explore the potential for structural variation and new growth at the synapse, we studied the morphological patterns of the end‐bulbs of cochlear nerve axons in adult cats by using rapid Golgi, reduced silver, and electron microscopic methods. Horseradish peroxidase labeling of these endings in the anterior division of the antroventral cochlear nucleus was produced by anterograde transport following injection into the cochlea. Three types of end‐bulbs were distinguished, regardless of method: reticular, coalescent, and ringed forms, all synapsing on spherical bushy cells. The reticular variety corresponds to the classically described end‐bulb and constitutes the majority in all regions of the tonotopic map. The ringed end‐bulb, described here for the first time, forms an excitatory synaptic cuff around the base of a bushy cell's main dendrite; these endings were localized to the region receiving cochlear input in the 1–6 kHz range, which is used in vocalization. The coalescent ending forms a small fraction of the end‐bulb population throughout the region studied. The findings raise the possibility of functional differences between these snyaptic types.Growth cones and retraction clubs were present on most, if not all, of the end‐bulbs in every adult cat studied. A systematic survey of the end‐bulb patterns revealed a continuous gradient of variation, in which each synaptic type forms a distinct mode. These findings lead us to hypothesize that the end‐bulbs are in a continual state of structural and functional flux. These endings should prove useful for studies on the modifiable properties of

ISSN:0887-4476    

DOI:10.1002/syn.890100404

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

年代:1992

数据来源: WILEY

摘要:

AbstractAgents that modify thiol groups have been shown to alter ligand binding at a variety of receptor sites. In addition, alkylation of sulfhydryls has been shown to block ion channel conductance. We studied the effects of thiol reagents on γ‐aminobutyric acid (GABA)‐activated chloride flux (36Cl−) and [3H]‐diazepam binding in mouse brain membrane preparation (microsacs). Incubation of microsacs in the presence of: mercuric chloride (HgC12), p‐chloromercuriphenylsulfonic acid (pCMBS), hydroxymercuribenzoate (HMB), n‐ethylmaleimide (NEM), or iodoacetic acid (IAA) attenuated GABA‐stimulated Cl−uptake. The thiol reagents reduced both maximal stimulation and the potency of GABA to induce Cl−uptake. Thiol reagent treatment decreased the affinity of high‐affinity [3H]‐muscimol equilibrium binding. Supernatant prepared from microsacs treated with pCMBS stimulated Cl−uptake in the absence of GABA agonist in microsacs unexposed to thiol reagents. The supernatant taken from pCMBS‐treated microsacs also stimulated [3H]‐diazepam binding. This effect was blocked by the addition of the GABA receptor antagonist bicuculline. The concentration of endogenous GABA in supernatant from pCMBS‐treated microsacs was sixfold greater than that in supernatant from control microsacs. This increase in levels of endogenous GABA by thiol reagents was due to both an increase in GABA release and a decreas

ISSN:0887-4476    

DOI:10.1002/syn.890100405

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

年代:1992

数据来源: WILEY

摘要:

AbstractPrevious work has demonstrated a complex neurochemical and neuroanantomical heterogeneity of the striatum in normal brains. The present research investigated whether the heterogeneous distribution of dopamine would be altered following unilateral injections of the neurotoxin 6‐hydroxydopamine into the substantia nigra of the rat. Four weeks following injection, the nucleus accumbens and subregions of the caudate‐putamen and substantia nigra were dissected and analyzed by HPLC with electrochemical detection for dopamine, 5‐hydroxytryptamine, and their respective metabolites. Levels of dopamine and its metabolites in the anterodrsolateral caudateputamen were depleted more than medial, posterior, and ventral, striatal areas in partially lesioned animals (<90% dopamine depletion). This resulted in an alteration of striatal heterogeneity such that a mediolateral gradient of dopamine tissue content was now superimposed on the normal rostrocaudal gradient observed in controls. Paralleling these findings, dopamine was more depleted in the lateral, as opposed to the medial, substantia nigra. These results indicate that the nigrostriatal dopamine system degenerates in a heterogeneous fashion following 6‐hydroxydopamine administration. It is speculated that the differential loss of dopamine neurons observed in the nigra of Parkinson's patients may be due to a differential sensitivity to toxins within th

ISSN:0887-4476    

DOI:10.1002/syn.890100406

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

年代:1992

数据来源: WILEY

摘要:

AbstractExperiments were performed to characterze the antagonistic activity and binding properties of SR 95531 [2‐(3′carbethoxy‐2′‐propyl)‐3‐amino‐6‐paramethoxy‐phenyl‐piridazinium bromide] in rat brain. SR 95531 and bicuculline methiodide inhibited muscimol‐stimulated36Cl−uptake in cortical synaptoneurosomes in a concentration‐dependent manner. The inhibitory potency of SR 95531 for the muscimol‐stimulated36Cl−uptake was 15 times higher than that of bicuculline methiodide. Scatchard plots of binding isotherms exhibited two apparent binding sites for [3H]SR 95531 in both the frontal cortex and cerebellum. The IC50value of SR 95531 for muscimol‐stimulated36Cl−uptake into cortical synaptoneurosomes was in close agreement with the KDvalue of low‐affinity binding sites of [3H]SR 95531 in the frontal cortex. Pretreatment of the membranes with phospholipase A2invariably decreased [3H]SR 95531 binding in the frontal cortex and cerebellum. On the other hand, the treatment significantly increased [3H]γ‐aminobutyric acid (GABA) binding in a concentration‐dependent manner in the frontal cortex. Although lower concentrations of phospholipase A2did not affect [3H]GABA binding in the cerebellum, treatment with higher concentrations of phospholipase A2increased the binding in this region. Specific binding of [3H]SR 95531 was also detected in cultures rich in cerebellar granule cells. Pretreatment with phospholipase A2affected the binding of [3H]GABA and [3H]SR 95531 in these cells, as in the case of the cerebellum. These effects of phospholipase A2on the binding of [3H]GABA and [3H]SR 95531 were partially prevented by the addition of delipidated bovine serum albumin. Furthermore, the products generated by the catalytic activity of phospholipase A2, such as arachidonic acid and lysophosphatidylcholine, mimicked the effects of phospholipase A2on the binding of [3H]GABA and [3H]SR 95531. These results suggest that SR 95531 exerts GABA‐antagonistic action through its low‐affinity binding site, and that exogenously added phospholipase A2induces the conversion of GABAAreceptors into the agonist‐preferential conformati

ISSN:0887-4476    

DOI:10.1002/syn.890100407

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

年代:1992

数据来源: WILEY

摘要:

AbstractIn the presence of spiperone to block the 5‐HT1A‐mediated inhibition of pyramidal cell activity, 5‐hydroxytryptamine (serotonin, 5‐HT) produces a rapid transient increase in amplitude of the extracellularly recorded population spike from area CA1 of the hippocampus. Intracellular recording techniques in area CA1 of rat hippcampal slices were used to identify the ionic mechanism and to characterize the 5‐HT receptor mediating this excitatory response to 5‐HT. Most of the experiments were conducted in the presence of spiperone to block the 5HT1Ahyperpolarization. Since spiperone also has high affinity for 5‐HT2receptors, any response mediated by 5‐HT2receptors would also be blocked. Bath perfusion of the slice with 5‐HT increased the rectification of pyramidal cells in the subthreshold region, increased the resistance, and increased the amplitude of subthreshold excitatry postsynaptic potentials (EPSPs) to initiate spike firing. The 5‐HT2,1C‐selective agonist DOI mimicked this effect of 5‐HT, and the 5‐HT2,1Cantagonist ketanserin (1 μM) blocked the effect of DOI. There was no change in the amplitude of the slow afterhyperpolarization (IPSPs). The increase in rectification and EPSP amplitude by 5‐HT occurred even in the presence of the 5‐HT4‐selective antagonist BRL 24924 to prevent the decrease in amplitude of the sAHP by 5‐HT. We conclude that 5‐HT produces a fast excitatory response by increasing subthreshold conductance in CA1 hippocampal pyramidal cells. The identity of the receptor mediating this response was not conclusively identifi

ISSN:0887-4476    

DOI:10.1002/syn.890100408

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

年代:1992

数据来源: WILEY

摘要:

AbstractCorticotropin‐releasing hormone (CRH), in addition to its neuroendocrine role, may act as a central neurotransmitter. Cerebral cortical CRH may have an important role in behavioral and neurodegenerative disorders. To gain an understanding of factors that may influence cortical CRH, we investigated the effect of several neurotransmitters and neuropeptides on the release of immunoreactive CRH (iCRH) from various cerebral cortical regions [frontal (FC), parietal (PC), temporal (TC), and occipital (OC)] in vitro. The hypothalamic release of iCRH was also evaluated under the same experimental conditions. Basal release of iCRH was approximately 2‐fold, and KC1‐stimulated iCRH release was approximately 4‐fold higher in the hypothalamus than in any of the cortical regions. Cortical iCRH release was stimulated by 10 nM somatostatin (SRIF) in PC and 1 nM neuropeptide Y (NPY) in TC. Cortical iCRH release was inhibited by 1 and 10 nM acetylcholine (ACh), 0.1 μM glutamate, and 10 nM NPY. These effects were confined to the FC and/or PC. Hypothalamic iCRH release was stimulated by 1 and 10 nM ACh, 10 μM GABA, and 1 and 10 nM serotonin but was inhibited by 10 nM SRIF and 1 μM GABA. Growth hormone‐releasing hormone did not affect cortical or hypothalamic iCRH release. These results demonstrate that CRH release from the cerebral cortex and the hypothalamus are under different regulatory mechanism(s). Furthermore, they indicate that the release of CRH in various cortical regions may be regulated differentially by the same neur

ISSN:0887-4476    

DOI:10.1002/syn.890100409

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

年代:1992

数据来源: WILEY

摘要:

AbstractWe have utilized intracellular recording techniques to investigate the cholinoceptivity of rat medial vestibular nucleus (MVN) neurons in a submerged brain slice preparation. Exogenous application of the mixed cholinergic agonists, acetylcholine (ACh) or carbachol (CCh), produced predominantly membrane depolarization, induction of action potential firing, and decreased input resistance. Application of the selective muscarinic receptor agonist muscarine (MUSC), or the selective nicotinic receptor agonists nicotine (NIC) or 1,1‐dimethyl‐4‐phenylpiperazinium (DMPP) also produced membrane depolarizations. The MUSC‐induced depolarization was accompanied by decreased conductance, while an increase in conductance appeared to underlie the NIC‐ and DMPP‐induced depolarizations. The muscarinic and nicotinic receptor mediated depolarizations persisted in tetrodotoxin and/or low Ca2+/high Mg2+containing media, suggesting direct postsynaptic receptor activation. The MUSC‐induced depolarization could be reversibly blocked by the selective muscarinic‐receptor antagonist, atropine, while the DMPP‐induced depolarization could be reversibly suppressed by the selective ganglionic nicotinicreceptor antagonist, mecamylamine. Some neurons exhibited a transient membrane hyperpolarization during the depolarizing response to CCh or MUSC application. This transient inhibition could be reversibly blocked by the γ‐aminobutyric acid (GABA) antagonist, bicuculline, suggesting that the underlying hyperpolarization results indirectly from the endogenous release of GABA acting at GABA receptors. This study confirms the cholinoceptivity of MVN neurons and establishes that individual MVN cells possess muscarinic as well as nicotinic receptors. The data provide support for a prominent role of cholinergic mechanisms in the direct and indirect regulation of the excitab

ISSN:0887-4476    

DOI:10.1002/syn.890100410

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

年代:1992

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890100401

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

年代:1992

数据来源: WILEY