摘要:

AbstractLong‐term potentiation (LTP) was studied in the hippocampal CA1 region of guinea‐pigs using a solution containing 0.1 mM magnesium and 10 μM of the non‐N‐methyl‐d‐aspartate (non‐NMDA) antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX), leaving an NMDA‐mediated field excitatory postsynaptic potential (EPSP). Brief high‐frequency afferent tetanization induced a substantial synapse‐specific potentiation of the NMDA EPSP with a time course closely resembling that previously described for LTP of the non‐NMDA‐mediated EPSP. This NMDA EPSP potentiation was occluded by prior induction of LTP in normal solution. Using a solution containing 0.1 mM magnesium and 1 μM CNQX, the EPSP was composed of both a non‐NMDA‐ and an NMDA‐mediated component which could be measured separately and in parallel. Manipulations that cause increased transmitter release, such as phorbol ester application and changes in stimulation frequency, enhanced the two measures nearly equally. Afferent tetanization induced an increase of both EPSP components, with a similar time course, the NMDA component showing a relative increase of about one‐third of that of the non‐NMDA one. These results suggest that, to the extent that LTP is based on an increased release of transmitter, the mechanism exhibits features distinct from tho

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00177.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractTo investigate the ability of mature regenerating retinal axons to form functional connections within central targets, severed axons were guided into the primary visual centres which subserve the pupillary constriction reflex in response to light. The ocular stump of the transected optic nerve of adult rats was connected by means of an autologous peripheral nerve graft with the pretectal region which contains the relay nucleus of pupillary constriction, the olivary pretectal nucleus. This nucleus is efferently connected with preganglionic neurons in the oculomotor nuclear complex which innervates parasympathetically the muscle constrictors of the iris. Six to sixteen weeks after optic nerve transection and peripheral nerve transplantation, brisk responses were observed in the pupils upon illumination of the transplanted eye. Recovery of the pupil responses indicated that retinal neurons used the peripheral nerve ‘bridge’ to access the pretectum, in which they established synaptic contacts in sufficient density and with appropriate specificity to reconstitute the function of the traumatically interrupted neuronal circui

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00178.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractDuring development, nerve growth factor (NGF) regulates the density and character of peripheral target innervation (Barde,Neuron,2, 1525–1534, 1989; Ritteret al., Soc. Neurosci. Abstr.,17, 546.2, 1991); its role in adult animals is less well defined. Here we have asked if the availability of growth factors such as NGF in peripheral tissues can influence the pattern of primary afferent connections in the CNS. Using osmotic minipumps, we raised the levels of NGF in rat skeletal musclein vivo, a tissue where the levels of this factor are normally very low (Korsching and Thoenen,Proc. Natl. Acad. Sci. USA,80, 3513–3516, 1983; Shelton and Reichardt,Proc. Natl. Acad. Sci. USA,81, 7951–7955, 1984; Goedertet al., Mol. Brain Res.,1, 85–92, 1986). After 2 weeks of treatment we asked if the sensory neurons innervating this tissue showed an altered strength and distribution of connections with dorsal horn neurons. The contralateral (vehicle‐treated) muscle, and totally untreated animals, served as controls. In normal and vehicle‐treated animals, electrical stimulation of muscle afferents excited relatively few neurons in the dorsal horn, and these generally showed only weak responses. In contrast, on the NGF‐treated side many more dorsal horn neurons in the lumbar enlargement of the spinal cord were excited by muscle afferents. The increased responsiveness could not be explained by a generalized increase in dorsal horn excitability, since spontaneous activity was not enhanced, nor by a change in A‐fibre‐mediated inhibitions from the treated afferents. Thus, these afferents appeared to establish new synaptic connections or strengthened previously weak ones as a result of increased neurotrophic factor availability. The data suggest that, in the adult rat, the levels of growth factors in peripheral targets may be used to regulate an appropriate degree of afferent connectivity within the centr

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00179.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractDifferent classes of potassium (K+) outward current activated by depolarization were characterized in relay neurons acutely isolated from the rat lateral geniculate nucleus (LGN), using the whole‐cell version of the patch‐clamp technique. A fast‐transient current (IA), activated at around –70 mV, declined rapidly with a voltage‐dependent time constant (τ= 6 ms at + 45 mV), was 50% steady‐state inactivated at –70 mV, and rapidly recovered from inactivation with a monoexponential time course (τ= 21 ms). IAwas blocked by 4‐aminopyridine (4‐AP, 2–8 mM) and was relatively insensitive to tetraethylammonium (TEA, 2–10 mM). After elimination of IAby a conditioning prepulse (30 ms to –50 mV), a slow‐transient K+current could be studied in isolation, and was separated into three components, IKm, IKsand a calcium (Ca2+)‐dependent current, IK[Ca]. The slow‐transient current was not consistently affected by 4‐AP (up to 8 mM), while TEA (2–10 mM) predominantly blocked IKsand IK[Ca]. The component IKmpersisted in a solution containing TEA and 4‐AP, activated at around –55 mV, declined monoexponentially during maintained depolarization (τ= 98 ms at +45 mV), was 50% inactivated at –39 mV, and recovered with τ= 128 ms from inactivation. IKsactivated at a similar threshold, but declined much slower with τ= 2662 ms at +45 mV. Steady‐state inactivation of IKswas half‐maximal at –49 mV, and recovery from inactivation occurred relatively fast with τ= 116 ms. From these data and additional current‐clamp recordings it is concluded that the K+currents, due to their wide range of kinetics and dependence on membrane voltage or internal Ca2+concentration, are capable of cooperatively controlling the firing threshold and of shaping the different states

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00180.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractAction potentials generated by voltage‐dependent Ca2+conductances were studied at 25°C with the perforated‐patch technique, in freshly dispersed adult rat sensory neurons perfused with Na‐free solutions containing tetraethylammonium. Brief depolarizing currents from membrane potentials negative to –75 mV always elicited long (>100 ms) plateau spikes which had different thresholds in different neurons: a low threshold around –60/–50 mV and a high‐threshold at –30/–20 mV. Stimulations from potentials positive to –55 mV, on the contrary, elicited spikes originating only in the high threshold region and sensitive to 25 μM Cd2+, designated high‐threshold spikes. In neurons which showed spikes with low threshold, addition of 25 μM Cd2+disclosed a smaller and shorter regenerative response, the low‐threshold spike. Moreover, the classical ‘anode‐break’ stimulation from –50/–60 mV uncovered isolated low‐threshold spikes, indicating a time‐ and voltage‐dependent de‐inactivating process. From the properties of the low (LVA) and high (HVA) voltage‐activated Ca2+currents, recorded under the same extracellular conditions, a Hodgkin–Huxley model was derived and used to reconstruct all the features of the recorded spikes. The model was also able to simulate experimental blocking of LVA channels by amiloride, modulation of HVA channels by baclofen and induced oscillatory firing. This agreement between the behaviour of recorded spikes and their mathematical description led us to conclude that the LVA and HVA Ca2+currents underlie the low‐ and high‐threshold Ca2+spikes, respectively. Furthermore, our data suggest that complex behaviour known to be typical of central nervous system n

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00181.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractThe protein complex promotingin vitroterminal differentiation of cerebellar granule cells has been isolated from rabbit serum. We designate the complex the neurite outgrowth and adhesion complex (NOAC). The apparent molecular weight, evaluated by gel filtration, is 80–100 kDa. Rat cerebellar granule cells cultured in NOAC exhibit much lower glial cell contamination and survive, in their differentiated state, much longer than in 10% foetal calf serum. While they bind tetanus toxin, express specific antigens such as synapsin l, synaptophisin and A2B5, and release [3H]d‐aspartate in a fashion similar to that shown by cells cultured in foetal calf serum, they show a 60% reduction in the total number of kainate binding sites. Excitatory amino acid (EAA)‐triggered and depolarization‐stimulated calcium influx, measured in the presence of different agonists, is 50–80% lower in NOAC‐cultured cells. NOAC cells are resistant to excitotoxic stimuli carried by EAAs or by depolarizing treatments with 50 mM KCI or 6 μM veratridine. The marked resistance of NOAC‐cultured neurons to EAAs can be attributed to decreased calcium entry through EAA‐coupled and voltage‐gated calcium channels and possibly to other, as yet unidentified, phenotypic properties of these cells. These findings demonstrate that rabbit serum contains one or more polypeptide(s) endowed with the properties of promotingin vitrosurvival and differentiation of rat cerebellar granule cells and of conferring an EAA

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00182.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractThe effect of phorbol esters on the light‐evoked responses of horizontal cells were studied in the turtle eyecup preparation. Phorbol esters caused a reduction in receptive field size and a significant decrease in the amplitude of responses to annular and full‐field illumination; however, they caused only minor changes in responses to small spots in the receptive field centre. The dark membrane potential was not affected. The results suggest that phorbol esters may affect both coupling resistance and membrane resistance in horizontal cells. The effects of phorbol esters were blocked by the protein kinase C inhibitor staurosporine, and inactive phorbol ester had no effect, making it very likely that the phorbol ester effects were mediated through activation of protein kinase C. The above effects of the phorbol esters were considerably reduced by the dopamine antagonists haloperidol and fluphenazine, suggesting that they were in part mediated by release of dopam

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00183.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractExperiments were performed in barbiturate‐anaesthetized, spinalized cats to investigate the effect of calcitonin gene‐related peptide (CGRP) on the spatial distribution of immunoreactive substance P (ir‐SP) in the spinal cord released by electrical nerve stimulation and noxious mechanical stimuli. The presence of ir‐SP was assessed with microprobes bearing C‐terminus‐directed antibodies to SP. CGRP was microinjected into the grey matter of the spinal cord near microprobe insertion sites at depths of 2500, 2000, 1500 and 1000 μm using minute amounts (in total 0.2–0.5 μl) of Ringer solution containing CGRP at a concentration of 10−5or 10−3M. In the untreated cord electrical stimulation of the tibial nerve (suprathreshold for all C fibres) elicited release of ir‐SP which was centred in and around the lamina II. After microinjection of CGRP, stimulation‐associated ir‐SP was detected in a region extending from the cord surface down to the ventral horn. This pattern was similar to that observed after the microinjection of synthetic peptidase inhibitors (Dugganet al., Brain Res.,579, 261–269, 1992). The large expansion of sites accessed by ir‐SP was time‐dependent, reaching a maximal effect within 10–40 min after microinjection of CGRP, and reversal was observed in subsequent probes. A similar expansion of the regions accessed by ir‐SP after microinjection of CGRP was also observed when release of ir‐SP was evoked by noxious mechanical stimulation of the toes. These results indicate that one important function of CGRP in the spinal cord may be the control of the intraspinal sites and neuronal circuits accessed by released substance P, possibly by inhibition of endopeptidase

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00184.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractIn vivoandin vitrotechniques were utilized to examine the influence of a protein synthesis blocker, cycloheximide (CHX), on the damaging effects of anoxia in the rat. CHX administered 1 h before transient (30 min) forebrain ischaemia increased the survival of animals, decreased body weight loss and reduced the occurrence of delayed degeneration in the CA1 pyramidal region. The same dose of CHX injected 1 h after ischaemia induced status epilepticus, a decrease in survival rate, and did not reduce weight loss or CA1 damage in any of the surviving rats. Electrophysiological techniques were then used to determine the effects of various periods of anoxia and aglycaemia (AA) on CA1 field excitatory postsynaptic potentials (EPSPs) in hippocampal slices incubated in the presence or absence of CHX. In CHX‐treated slices, recuperation of EPSP amplitude (45±16%) was significantly greater than in control slices (9±9%) following an AA episode of 3 min 45 s. No difference was seen in the percent recuperation of EPSPs in the control and CHX‐treated slices after shorter or longer episodes of AA. From these studies, it appears that CHX protects against the damaging effect of ischaemiain vivoor AAin

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00185.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractIncorporation of [35S]methionine into proteins and two‐dimensional gel autoradiograms was used to characterize early post‐anoxia–aglycaemia protein synthesis in the CA1 area of rat hippocampal slices maintainedin vitro.We have compared the effects of 3–4 min and 5–10 min insults, since the former but not the latter produces a reversible block of synaptic transmission (see companion paper). An insult of between 3 min 30 s and 4 min induces a transient increase in the labelled proteins during the first hour of reoxygenation, as compared to control. The increase in protein synthesis is conspicuous for several proteins, including actin, α‐tubulin and heat‐shock proteins (hsp70c and hsp90), as determined by immunoblotting. In the case of α‐tubulin, we show within situhybridization and polymerase chain reaction procedures that the increase in protein synthesis is associated with a marked increase in the expression of the corresponding messenger RNAs. The results demonstrate that, in addition to regulatory proteins such as hsps, the synthesis of several polypeptides, including those associated with the cytoskeleton, is altered

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00186.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY