摘要:

AbstractMore effective measures to control and replace the dopaminergic deficit of Parkinson's disease are being actively sought. One basic problem is how the striatal dopamine loss should be replaced in order to mimic most accurately the physiological state. Animal electrophysiology indicates that the dopaminergic nigrostriatal pathway has a dual tonic and phasic action. Intermittent dopaminergic stimulation is associated with behavioural hyposensitivity both in animal models and in patients with Parkinson's disease. Continuous dopaminergic stimulation provides a tonic background and improves some clinical problems but is also associated with tolerance. None of the available pharmacological approaches can restore the dopamine deficiency of Parkinson's disease to physiological levels. Continuous dopaminergic stimulation for<24 h, associated with small doses of levodopa or a short‐acting dopamine agonist, appears to be the best, albeit imperfect, therapeutic approach until other, more efficacious remedies are develope

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00584.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractSeventeen callosally projecting axons originating near the border between areas 17 and 18 in adult cats were anterogradely labelled with biocytin and reconstructed in 3‐D from serial sections. All axons terminated near the contralateral 17/18 border. However, they differed in their diameter, tangential and radial distributions, and overall geometry of terminal arbors. Diameters of reconstructed axons ranged between 0.45 and 2.25 μm. Most of the axons terminated in multiple terminal columns scattered over several square millimetres of cortex. Thus in general callosal connections are not organized according to simple, point‐to‐point spatial mapping rules. Usually terminal boutons were more numerous in supragranular layers; some were also found in infragranular layers, none in layer IV. However, a few axons were distributed only or mainly in layer IV, others included this layer in their termination. Thus, different callosal axons may selectively activate distinct cell populations. The geometry of terminal arbors defined two types of architecture, which were sometimes represented in the same axon: parallel architecture was characterized by branches of considerable length which supplied different columns or converged onto the same column; serial architecture was characterized by a tangentially running trunk or main branch with radial collaterals to the cortex. These architectures may relate to temporal aspects of inter‐hemispheric interactions. In conclusion, communication between corresponding areas of the two hemispheres appears to use channels with different morphological and probably functional pr

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00585.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractWe analysed the activation profiles obtained by simulating invasion of an orthodromic action potential in eleven anterogradely filled and serially reconstructed terminal arbors of callosal axons originating and terminating in areas 17 and 18 of the adult cat. This was done in order to understand how geometry relates to computational properties of axons. In the simulation, conduction from the callosal midline to the first bouton caused activation latencies of 0.9‐3.2 ms, compatible with published electrophysiological values. Activation latencies of the total set of terminal boutons varied across arbors between 0.3 and 2.7 ms. Arbors distributed boutons in tangentially segregated terminal columns spanning one or, more often, several layers. Individual columns of one axon were frequently activated synchronously or else within a few hundred microseconds of each other. Synchronous activation of spatially separate columns is achieved by: (i) long primary or secondary branches of similar calibre running nearly parallel to each other for several millimetres; (ii) variations in the calibre of branches serially fed to separate columns by the same primary or secondary branch; (iii) exchange of high‐order or preterminal branches across columns. The long, parallel branches blatantly violate principles of axonal economy. Simulated alterations of the axonal arbors indicate that similar spatiotemporal patterns of activity could, in principle, be obtained by less axon‐costly architectures. The structure of axonal arbors, therefore, may not be determined solely by the type of spatiotemporal activation profiles it achieves in the cortex but also by other constraints, in particular those imposed by developmental mecha

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00586.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe distributions of the mRNAs encoding thel‐glutamate transporters GLT1 and GLAST were examined in the rat brain byin situhybridization using35S‐labelled oligonucleotide probes. Probes directed to GLT1 produced dense labelling in the hippocampus, neocortex and neostriatum, and weak labelling in the cerebellum. In contrast, GLAST mRNA appeared to be greatly enriched in the cerebellum compared to other brain regions. While the intensity of the labelling for GLAST and GLT1 varied among different regions, their cellular distributions appeared to coincide inasmuch as both mRNAs were mainly expressed by glial cells. Labelling occurred,inter alia, in glial cells throughout the hippocampus, and in Golgi epithelial cells in the Purkinje cell layer of the cerebel

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00587.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractCa2+channel currents were recorded in undifferentiated human neuroblastoma (SH‐SY5Y) cells with the whole‐cell patch‐clamp technique, using 10 mM Ba2+as charge carrier. Currents were only evoked by depolarizations to ‐30 mV or more positive (holding potential ‐80 mV), inactivated partially during 200 ms depolarizing steps, and were abolished by 150 μMCd2+. Currents could be enhanced by Bay K‐8644 and partially inhibited by nifedipine, suggesting that they arose in part due to activation of L‐type Ca2+channels. Currents were also inhibited by the marine snail peptide ω‐conotoxin GVIA (ω‐CgTx). At a concentration of 10 nM inhibition by ω‐CgTx was reversible, but at higher concentrations blockade was always irreversible. Although current inhibition by nifedipine was maximal at 1μM, supramaximal concentrations reduced the inhibitory actions of ω‐CgTx in a concentration‐dependent manner. Ca2+channel currents evoked from a holding potential of ‐50 mV showed no inactivation during 200 ms depolarizations but declined in amplitude with successive depolarizing steps (0.2 Hz). Current amplitudes could be restored by returning the holding potential to ‐80 mV. Currents evoked from ‐50 mV were inhibited by nifedipine and ω‐CgTx to a similar degree as those evoked from ‐80 mV. Our results indicate that undifferentiated SH‐SY5Y cells possess L‐ and N‐type Ca2+channels which can be distinguished pharmacologically but cannot be separated by using depolarized holding potentials. Furthermore, these data suggest that nifedipine has a novel action to

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00588.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractIntracellular recording from CA1 neurons of the rat hippocampal slice preparation was used to examine the possibility of functional interactions between 5‐hydroxytryptamine (5‐HT) and thyrotropin releasing hormone (TRH), which act as cotransmitters in other areas of the central nervous system. 5‐HT (30 μM) elicited complex effects consisting of biphasic changes in membrane potential and a strong depression of the afterhyperpolarization (AHP) following a spike burst. TRH (10 μM) did not alter membrane potential or input conductance but it produced a partial block of the AHP. Under single‐electrode voltage clamp, 5‐HT and TRH both reduced the amplitude of voltage‐activated total K+currents. When the two substances were co‐applied, their actions were occluded. The voltage‐activated K+current remaining in Ca2+‐free solution lost its sensitivity to 5‐HT and TRH, suggesting that the K+current modulated by TRH and 5‐HT was Ca2+‐dependent, although TRH itself did not depress high‐threshold voltage‐activated Ca2+currents. When a relatively small concentration (5 μM) of 5‐HT was co‐applied with an equimolar amount of TRH, the degree of block of the spike AHP was the sum of the two individual effects of these drugs. It is suggested that in hippocampal pyramidal cells 5‐HT and TRH influenced neuronal excitability by depressing a Ca2+‐dependent K+current, a phenomenon perhaps mediated through a common

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00589.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractIntracellular recordings in rat hippocampal slices were used to examine how exogenous and endogenous cholinergic agonists modulate the firing pattern of intrinsically burst‐firing pyramidal cells. About 24% of CA1 pyramidal cells generated all‐or‐none, high‐frequency bursts of fast action potentials in response to intracellular injection of long positive current pulses. Application of carbachol (5 μM) converted burst firing in these neurons into regular trains of independent spikes. Acetylcholine (5 μM) exerted a similar effect, provided acetylcholine esterase activity was blocked with neostigmine (2 μM). Atropine (1 μM) reversed this cholinergic effect, indicating its mediation by muscarinic receptors. Cholinergic agonists also caused mild neuronal depolarization but the block of intrinsic burst firing was independent of this effect. Repetitive stimulation of cholinergic fibres in the presence of neostigmine (2 μM) evoked a slow cholinergic excitatory postsynaptic potential (EPSP) lasting about a minute. During the slow EPSP, burst firing could not be evoked by depolarizing pulses and the neurons fired in regular mode. These effects were prevented by pretreatment with atropine (1 μM). Exogenously applied cholinergic agonists and endogenously released acetylcholine also reduced spike frequency accommodation and suppressed the long‐duration afterhyperpolarization in burst‐firing pyramidal cells in an atropine‐sensitive manner. A membrane‐permeable cAMP analogue (8‐bromo‐cAMP; 1 mM) also reduced frequency accommodation and blocked the long‐duration afterhyperpolarization, but did not affect intrinsic burst firing at all. Taken together, the data show that muscarinic receptor stimulation transforms the stereotyped, phasic response of burst‐firing neurons into sti

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00590.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe behavioural effects of an early period of monocular deprivation can be extremely profound. However, it is possible to achieve a high degree of recovery, even to normal levels of visual acuity, by prompt imposition of certain regimes of part‐time reverse occlusion where the initially non‐deprived eye is occluded for only part of each day in order to allow a daily period of binocular visual exposure. In this paper we report on the depth perception of five monocularly deprived cats that had recovered normal visual acuity in both eyes following imposition of certain of the above occlusion regimes. Although three of the animals exhibited five‐to sevenfold superiority of binocular over monocular depth thresholds, subsequent tests made on two of the animals revealed that they were unable to make stereoscopic discriminations with random‐dot stereograms. Despite the recovery of normal visual acuity in both eyes, we conclude that these animals recover at best only local ste

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00591.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe monoclonal antibody (mAb) PC3.1 recognizes a subset of neurons distributed in the infragranular layers of the lateral neocortex of the rat. Immunoaffinity chromatography with mAb PC3.1 showed that this antibody specifically binds a peptide epitope on a 29 kDa protein named latexin. To study the molecular details of the protein, we isolated four independent cDNA clones for latexin from cDNA libraries of the rat cerebral cortex and whole brain using the amino acid sequences of latexin fragments. Analysis of these cDNA clones showed that the predicted primary structure of latexin consists of 223 amino acids, and has no strict homology to any sequences so far known. Western and Northern blots demonstrated that the latexin and its mRNA were expressed predominantly in neural tissues with some expression in non‐neural tissues. The gene that encodes latexin in the rat appeared to have homologues in other mammalian species and in the chick.In situhybridization showed that latexin mRNA is synthesized in a subset of neurons in the lateral but not the dorsal neocortex, and that the distribution profile of these neurons is quite similar to that of neurons expressing latexin. These results indicate that latexin is a novel class of neuronal protein which represents intracortical regionality, and suggest that the regional specification of the neocortex involves selective parcellation of neurons which express a particular gen

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00592.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractStudies of the early development of the mammalian cerebral cortex have revealed that the earliest generated neurons that form the primordial plexiform layer (also called preplate or marginal zone) distribute among layer I and layer VII (subplate). By means of bromodeoxyuridine labelling of cells becoming postmitotic, we have found evidence that, in the rat, an additional group of neurons of the primordial plexiform layer remains in the close vicinity of the ventricular zone. This finding, in line with the proposal by Marín‐Padilla (Z Anat. Entwicklungsgesch.,134, 117‐145, 1971), implies that the primordial plexiform layer suffers a tripartition after the formation of the cortical plate and of the intermediate zone (the latter soon becomes the embryonic white matter). Thus, primordial plexiform layer derivatives are in layer I, layer VII (subplate) and in the lower part of the embryonic white matter. This early generated neuronal population is also revealed with an antibody that recognizes the larger (67 kDa) isoform of glutamic acid decarboxylase (Kaufmanet al., Science,232, 1138‐1140, 1986). This is in accord with the earlier finding of a GABA‐containing cell population showing a similar spatiotemporal distribution. The early generated neurons of the embryonic white matter migrate tangentially and, in early postnatal animals, are found as interstitial cells in the medial regions of the subcortical white matter and at the midline in the corpus callosum. At caudal levels, similar cells invade the subpyramidal strata of the developing hippocampus. This tangential migration might explain the tangential dispersion of neural cell clones described in recent studies of cell lineage in the cerebra

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00593.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY