摘要:

AbstractRhesus monkeys (Macaca mulatta) were trained to discriminate among many complex naturalistic scenes. The scenes were still frames from a cinema film. They were presented as the discriminative stimuli in a concurrent discrimination learning task in which each discriminative stimulus was presented on one trial each day. Learning of this task was severely impaired by fornix transection. The same animals were also deficient in a similar concurrent discrimination learning task, with each discriminative stimulus presented on one trial each day, but with objects, not complex scenes, as the stimulus material. The impairment in object discrimination learning in the present experiment is attributable to an interaction of object discrimination learning with scene discrimination learning, and can be understood as an effect of interference in long‐term memory. In contrast to these impairments in long‐term memory, a test of within‐session learning of complex scenes, in which the average interval between successive presentations of the same stimulus was<3 min, was performed without significant impairment by the fornix‐transected animals. These results show that long‐term memory for complex naturalistic scenes reveals analogues in the monkey of human episodic memory and its impairment i

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00886.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractTwo developmentally regulated isoforms of the inhibitory glycine receptor harbouring different α subunit variants, GlyRN(neonatal) and GlyRA(adult), have previously been identified in rodent spinal cord. Primary cultures of embyronic spinal neurons, however, express predominantly GlyRN. Here,N‐methyl‐d‐aspartate (NMDA) receptor antagonists were found to significantly increase glycine receptor levels in mouse spinal cord cultures. In the presence of 2‐amino‐5‐phosphonovalerate or MK‐801 (dizocilpine), both GlyRNand GlyRAcontents were elevated, as revealed by isoform‐selective immunoassays and amplification of corresponding α subunit transcripts by the polymerase chain reaction. This effect of NMDA receptor antagonists was restricted to a ‘sensitive’ period within the second week after plating. Apparently, NMDA receptor‐mediated glutamate neurotoxicity prevented GlyRAaccumulation under standard culture conditions. Our data indicate that neuronal maturation in cell culture depends on conditions which minimize cell death resulting from glutamate release

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00887.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractNorthern blot analysis was used to examine the effects of glucocorticoids on neurotrophin mRNA expression in the rat cerebral cortex and hippocampus. The results show that 3 days after adrenalectomy the mRNA levels for nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF) and neurotrophin‐3 (NT‐3) decreased significantly in both these regions. In adrenalectomized animals given dexamethasone replacement the mRNA levels for the three neurotrophins were restored to control levels. The effect of a single dose of dexamethasone (5 mg/kg) administered i p. to intact animals on the expression of neurotrophins was also examined. NGF and NT‐3 mRNAs showed a 2.5‐fold and a 1.4‐fold increase, respectively, during the first 4 h after the injection. The increase was followed by a decrease, with levels ‐50% of control 24 and 48 h after the injection. In contrast, the level of BDNF mRNA did not change during the first 10 h after the injection, but decreased to 70% of control 48 h after the injection. These data indicate that glucocorticoids regulate neurotrophin mRNA expression both in the cortex and in the hippocampus, and suggest further that the known effects of glucocorticoids on neuronal survival in the brain could be due to changes in the levels of neurotrophins

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00888.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractGlucocorticoid hormones are important regulators of brain development and ageing. Here we show that dexamethasone, a synthetic glucocorticoid, differentially affects the expression of nerve growth factor (NGF) in cultured neurons and astrocytes. Dexamethasone increased the levels of NGF mRNA in cultured hippocampal neurons in a time‐ and concentration‐dependent manner, whereas it down‐regulated the NGF mRNA levels in astrocytes. However, dexamethasone had no effect on the mRNA levels of brain‐derived neurotrophic factor in the hippocampal neurons. Aldosterone, a mineralocorticoid, in higher concentrations also up‐regulated NGF mRNA levels in the hippocampal neurons. Dexamethasone increased the levels of NGF mRNA in the rat hippocampusin vivo, but not to the same extent as observed with kainic acid, a glutamate receptor agonist. There is no apparent diurnal rhythm in the hippocampal NGF protein levels corresponding to circadian variations in the levels of glucocorticoid hormones in serum. The increase in NGF mRNA in the hippocampusin vivofollowing dexamethasone treatments may reflect the physiological response of hippocampal neurons to high glucocorticoid levels reached under conditions

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00889.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractThe effects of antagonists and agonists of the platelet‐activating factor (PAF) receptor on the formation of long‐term potentiation (LTP) were examined in slices of rat hippocampus. The antagonisttrans‐BTD (trans‐2,5‐bis‐(3,4,5‐trimethoxyphenyl)‐1,3‐dioxolane) at concentrations of 8–16 μM blocked LTP in field CA1 while the same concentration of a stereo isomer (cis‐BTD) with low affinity for PAF receptors was without effect. CV3988, an antagonist structurally related to PAF, also attenuated LTP. The blockade of LTP bytrans‐BTDwas partially reversed by simultaneous application of the non‐metabolizable receptor agonist carbamyl‐PAF. Trans‐BTD did not change the following physiological measures: (i) paired‐pulse facilitation, (ii) responses occurring during the short bursts given to induce LTP, (iii)N‐methyl‐d‐aspartate receptor‐mediated responses, and (iv) potentiation measured during the first minute after high‐frequency stimulation. It thus appears thattrans‐BTD interferes with LTP at some step after induction and initial expression. These results suggest that activation of PAF receptors contributes to the stabilization of LTP, possibly v

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00890.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractNitric oxide production in the cerebellum and induction of long‐term potentiation (LTP) in the hippocampus have some characteristics in common: both phenomena are induced by activation ofN‐methyl‐D‐aspartate receptors and both are highly dependent on calcium‐mediated processes. Here we provide evidence that endogenous nitric oxide production is necessary for synaptic plasticity in the CA1 hippocampus of the rat. LTP recorded in slices was blocked in a concentration‐dependent manner by the nitric oxide synthase inhibitors L‐NG‐nitroarginine and L‐NG‐nitroarginine methyl ester, but L‐NG‐monomethylarginine was only marginally active. Bathing the slices with haemoglobin, a protein that scavenges nitric oxide, also resulted in a concentration‐dependent blockade of LTP. Nitric oxide released locally from hydroxylamine produced a stable potentiation of synaptic transmission that was not additive with LTP induced by high‐frequency stimulation. These results are fully consistent with the presumed retrograde messenger

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00891.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractIn mouse striatal neurons in primary culture, the maximal increase in intracellular cyclic guanosine monophosphate level evoked byN‐methyl‐d‐aspartic acid (NMDA) receptor activation was twice that induced by kainate, KCI and ionomycin. Quisqualate was almost inactive. All responses were mediated by nitric oxide (NO) production since they were blocked by haemoglobin (a NO scavenger) and byL‐NG‐monomethylarginine andL‐NGnitroarginine, the effects of both arginine analogues being reversed by an excess of L‐arginine. Several results indicate that NMDA receptors stimulate a specific NO synthase activity. This specifically NMDA‐activated NO synthase was blocked by nanomolar concentrations ofL‐NGnitroarginine, whereas the responses evoked by other agents, including kainate, KCI and ionomycin, were only blocked by micromolar concentrations of this NO synthase inhibitor. The NMDA response could not be totally reproduced by an increase in cytosolic calcium (Ca2+) alone. In contrast, in the presence of staurosporine, an inhibitor of protein kinases C (PKC), as well as after desensitization of PKC induced by long‐term treatment with the phorbol ester, phorbol‐12, 13‐dibutyrate, NMDA‐stimulated NO production was selectively reduced, reaching the level evoked by kainate or Ca2+increase. In conclusion, our results suggest that in striatal neurons, NMDA selectively stimulates a NO synthase activity which is inhibited by low concentrations ofL‐NGnitroarginine, throug

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00892.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractThe mechanism by which nerve ‐ muscle contacts are reduced during postnatal development of the rat soleus muscle was investigated using electrophysiological methods. Between days 7 and 9 after birth, soleus muscle fibres lose 0.19–0.24 terminals per muscle fibre within 24 h. A much more rapid loss of contacts is seen when muscles are exposedin vitroto acetylcholine (10−3g/ml). In this case 0.67–0.87 terminals per muscle fibre lose contact within 2 h. The loss of neuromuscular contacts induced by acetylcholine can be reduced by preincubating the muscles in solutions containing acetoxymethyl ester of 1,2‐bis(2‐amino‐phenoxylethane‐N,N1;N1‐tetraacetic acid (BAPTA‐AM), a Ca2+chelating agent that enters cells and reduces the Ca2+transients inside the cell. Treatment of muscles with nifedipine, which blocks dihydropyridine‐sensitive (L‐type) Ca2+channels, also reduced the acetylcholinesterase‐induced loss of neuromuscular contacts. The results indicate that transient increases in Ca2+inside nerve terminals contribute to loss of neuromuscular contacts, and that these increases occur by Ca2+entr

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00893.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractLevels of messenger RNA (mRNA) encoding glutamic acid decarboxylase (GAD) and preproenkephalin (PPE) were measured by Northern blot andin situhybridization analyses in the striatum of the rat, after chronic injections of two neuroleptics, sulpiride and haloperidol. The Northern blot analysis showed that the chronic injection of sulpiride at high doses (80 mg/kg, twice a day, 14 days) increased striatal GAD and PPE mRNA levels by 120% and 78% respectively, when compared to vehicle‐injected rats. Haloperidol injections at relatively low doses (1 mg/kg, once a day, 14 days) produced parallel increases in GAD (40%) and PPE (52%) mRNA levels. Afterin situhybridization densitometric measurements were performed on autoradiograms from rats treated with sulpiride, haloperidol or vehicle. The distribution of GAD and PPE mRNA signals in control rats was homogeneous along the rostrocaudal extension of the striatum. A similar increase was found along this axis after sulpiride (20%) and haloperidol (30%) treatments. The cellular observation of hybridization signals showed that grain density for GAD mRNA was increased in a majority of striatal cells after both treatments. By contrast, the PPE mRNA hybridization signal only increased in a subpopulation of neurons. The effects of such treatments were also analysed by measuring GAD activity in the striatum and in its output structures, the globus pallidus and the substantia nigra. After the administration of sulpiride, GAD activity was not modified in the striatum but increased in the globus pallidus (by 17%). After haloperidol treatment, GAD activity was increased in the globus pallidus (20%) and the substantia nigra (17%). It is concluded that the interruption of dopaminergic transmission, more precisely the D2receptor blockade, promotes in striatopallidal neurons an increase in GAD mRNA accompanied by an increase in GAD activity and PPE mRNA. A possible regulation of GAD mRNA and GAD activity in striatonigral neurons is also discusse

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00894.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

AbstractWe have derived two monoclonal antibodies, MF‐1 and MF‐2, which both recognize the same 58‐kD antigen. Light and electron microscopic immunocytochemistry showed that this antigen is highly expressed in the large mossy fibre terminals innervating the proximal portion of the apical dendrites of pyramidal neurons in hippocampal field CA3. Staining was seen in the adult hippocampus in rats and mice, and in a post mortem human sample. Comparison with the Timm stain showed that the antibodies recognize mossy fibres from all parts of the adult dentate gyrus except for the tip of the infrapyramidal blade (the latest part of the dentate gyrus to develop). The MF antigen is expressed by mature terminals, and is not detected immunohistochemically in developing hippocampal mossy terminals until the end of the first postnatal week (i.e. later than the Timm‐positive material). It was also found in host mossy fibre terminals innervating embryonic CA3 pyramids transplanted into adult hosts, but not in areas of the graft containing transplanted CA1 pyramids. These results indicate that this previously undescribed, late‐developing antigen provides a useful specific marker for the mossy fibre projection in both the normal hippocampus and in situations of experimentally manipulated con

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1992.tb00895.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY