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1. |
NMDA‐dependent heterosynaptic long‐term depression in the dentate gyrus of anaesthetized rats |
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Synapse,
Volume 10,
Issue 1,
1992,
Page 1-6
Brian R. Christie,
Wickliffe C. Abraham,
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摘要:
AbstractThis report examines the inductive mechanism involved in long‐term heterosynaptic depression (LTD) in the dentate gyrus of anaesthetized rats. Associative and non‐associative stimulus protocols were implemented, using the ipsilateral medial and lateral perforant path inputs to the dentate gyrus as the test pathways. In all experiments, the medial perforant path (MPP) received the conditioning stimuli which consisted of eight stimulus trains of 2 s duration, spaced 1 minute apart. Within each train the stimuli occurred as a burst of 5 pulses at 100 Hz, repeated at 200 ms intervals. The lateral perforant path (LPP) served as the test pathway in all of the initial experiments. In the associative condition, it received single pulses equally spaced between the medial path bursts. In the non‐associative condition, no lateral path stimuli were given during the medial path trains, In both condition, the application of the conditioning stimuli resulted in a long‐term potentiation (LTP) of the medial path evoked responses (P<0.001), while the lateral path responses showed LTD (P0.05) An occlusion test also showed there to be no further decreases in synaptic efficacy with the associative paradigm after the lateral path synapses were saturated with non‐associative LTD. The N‐methyl‐D‐aspartate (NMDA) receptor antagonist CPP (3‐((+)‐2‐carboxypiperazin‐4‐yl)‐propyl‐1‐phosphonic acid; 10 mg/kg) blocked the appearance of LTP and LTD in both conditions, and in fact, the lateral path responses in the associative condition actually showed a significant degree of enhancement (P<0.001). This enhancement was also evidenced when the lateral path stimuli were administered alone without prior CPP administration (P<0.05). The results imply that one set of common mechanisms is utilized in the induction of LTD in the dentate gyrus, whether the medial and lateral paths are activated in an associ
ISSN:0887-4476
DOI:10.1002/syn.890100102
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1992
数据来源: WILEY
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2. |
Action of serotonin in the medial prefrontal cortex: Mediation by serotonin3‐like receptors |
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Synapse,
Volume 10,
Issue 1,
1992,
Page 7-15
Charles R. Ashby,
Emmeline Edwards,
Rex Y. Wang,
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摘要:
AbstractIn the present study, we investigated the effects of various serotonin (5‐HT) antagonists on 5‐HT's action on medial prefrontal cortical cells (mPFc) using the techniques of single cell recording and microintophoretic The microiontophoretic application of 5‐HT (10–80 nA) produced a current‐dependent suppression of mPFc cell firing and this effect was blocked by the selective 5‐HT3receptor antagonists (±)‐zacopride, ICS 205930 and granisetron at currents of 5–20 nA. Furthermore, the intravenous (i.v.) administration of (±)‐zacopride (5–50 μg/kg) markedly attenuates the suppressive action of 5‐HT on mPFc cell firing. In contrast, the microinotophoresis of 5‐HT1and 5‐HT2receptor antgonists such as (±)‐pindolol, spiperone, metergoline, and ritanserin (10–20 nA) failed to block 5‐HT's effect. In fact, in some cells, spiperone and ritanserin potentiated 5‐HT's action and prolonged neuronal recovery. In addition, the intravenous administration of either ritanserin (5–2,000 μg/kg) or metergoline (4–2,400 μg/kg) failed to alter 5‐HT's action. The electrical stimulation of the caudal linear raphe nucleus (CLi) suppressed the spontaneous activity of 83% of the mPFc cells tested by 45 ± 2%. This suppression was significantly attenuated by the iontophoresis of granisetron (2.5–5 nA) but not by the 5‐HT2and 5‐HT1Creceptor antagonist ritanserin or the relatively selective 5‐HT2receptor antagonist (+)‐MDL 11,939 (10–40 nA). However, the i.v. administration of ritanserin (0.5–1.5 mg/kg) or S‐zacopride (0.1 mg/kg) significantly blocked the suppression of mPFc cell firing produced by CLi stimulation. Overall, our results suggest that 5‐HT's physiological effect in the mPFc may be primarily mediated by its interaction with 5‐HT3‐like receptors and that ritanserin's blo
ISSN:0887-4476
DOI:10.1002/syn.890100103
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1992
数据来源: WILEY
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3. |
Compartmental distribution of cytochrome oxidase in the striatum of the rat |
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Synapse,
Volume 10,
Issue 1,
1992,
Page 16-24
Sarah J. Augood,
Piers C. Emson,
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摘要:
AbstractEndogenous cytochrome oxidase activity was investigated in the adult rat striatum at the light microscope level to see if it was distributed in accordance with the established striatal patch/matrix compartmentalisation. Striatal sections stained to visualise cytochrome oxidase activity were compared with serial sections stained to visualise tyrosine hydroxylase and calbindinD28k‐like immunoreactivity, established markers of the matrix compartment. The distribution of endogenous cytochrome oxidase activity was found to coincide with the immunocytochemical staining pattern seen for tyrosine hydroxylase and calbindinD28kwhereby areas of intense tyrosine hydroxylase and calbindinD28k‐like immunoreactivity (termed the matrix) corresponded to areas of intense cytochrome oxidase activity. Conversely, areas of less intense tyrosine hydroxylase and calbindinD28k‐like immunoreactivity (termed patches) corresponded to areas of low cytochrome oxidase activity. In addition, the distribution of two other oxidative enzymes involved in the regulation of mitochondrial respiration, succinic dehydrogenase and NADH‐diaphorase, was examined in the striatum and substantia nigra by using histochemical techniques. Both NADH‐diaphorase and succinic dehydrogenase histochemistry showed an uneven pattern of neuropil staining in the striatum. In the substantia nigra a few intensely stained cell bodies were seen in the dorsal‐lateral tip of the pars reticulata with both histochemical techniques. By using an anti‐cytochrome oxidase antibody an abundance of immunoreactive cell bodies and processes were seen in the substantia nigra, particularly in the dorso‐medial rim and dorsal tip of the pars reticulata. The substantia nigra pars lateralis contained many intensely stained cytochrome oxidase‐like immunoreactive cell bodies and processes. Our results demonstrate that the neurochemically distinct compartments of the adult rat striatum contain differential amounts of endogenous cytochrome oxidase activity suggesting that the matrix compartment is more metabolically active than the patch compartment. This difference in metabolic activity may reflect a difference in synaptic activity between the two stri
ISSN:0887-4476
DOI:10.1002/syn.890100104
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1992
数据来源: WILEY
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4. |
Electrophysiological profile of the new atypical neuroleptic, sertindole, on midbrain dopamine neurones in rats: Acute and repeated treatment |
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Synapse,
Volume 10,
Issue 1,
1992,
Page 25-33
Torben Skarsfeldt,
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摘要:
AbstractSertindole (Lundbeck code No. Lu 23‐174) (1‐[2‐[4‐[5‐chloro‐1‐(4‐fluorophenyl)‐1H‐indol‐3‐yl]‐1‐piperidinyl]ethyl]‐2‐ imidazolidinone) is a new potential neuroleptic compound.After 3 weeks of treatment sertindole shows an extreme selectivity to inhibit the number of spontaneously active dopaminergic (DA) neurones in ventral tegmental area (VTA) while leaving the number of active DA neurones in substantia nigra pars compacta (SNC) unaffected. Acute injection of apomorphine or baclofen reverse the inhibition of activity seen after repeated treatment with sertindole. This suggests that sertindole induces a depolarization inactivation of the DA neurones. The depolarization inactivation is reversible since normal activity of DA neurones is found in both SNC and VTA after two weeks withdrawal from repeated treatment with a low dose with sertindole. One or two weeks administration of a high dose of sertindole induced only minor effects on the DA neurones in VTA; i.e., in order to obtain the depolarization inactivation sertindole requires 3 weeks of treatment as has also been reported for other neuroleptics.Three weeks of treatment with clozapine induces a selective inhibition of the active DA neurones in VTA but at much higher doses than seen with sertindole, while haloperidol induces a non‐selective decrease of spontaneously active DA neurones in both areas.In acute electrophysiological experiments intraveneous (i.v.) administration of sertindole—in contrast to both clozapine and haloperidol—neither reverse d‐amphetamine‐ nor apomorphine‐induced inhibition of the firing frequencies of DA neurones in SNC or in VTA. In addition, sertindole does not—even in high doses—increase the firing frequency of DA neurones in SNC or VTA.In conclusion the study indicates that sertindole is a potential antipsychotic compound which should induce fewer extrapyramidal side
ISSN:0887-4476
DOI:10.1002/syn.890100105
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1992
数据来源: WILEY
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5. |
Cholinergic and GABAergic mediations of the effects of apomorphine on serotonin neurons |
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Synapse,
Volume 10,
Issue 1,
1992,
Page 34-43
H. Y. Chen,
Y. P. Lin,
E. H. Y. Lee,
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摘要:
AbstractApomorphine (APO) has been shown to elevate tryptophan, serotonin (5‐HT), and 5‐hydroxyindoleacetic acid (5‐HIAA) concentrations in the dorsal raphe (DR) and its corresponding projection site, the striatum, but not in the median raphe (MR) and its terminal area, the hippocampus. We have previously demonstrated that these effects are indirectly mediated through dopamine (DA) autoreceptors in the substantia nigra and possibly γ‐aminobutyric acid (GABA) neurons in or near the DR. In the present study, we have further found that the effects of APO on 5‐HT neurons are also mediated through both nicotinic and M1muscarinic cholinergic receptors as well as GABAAreceptors in the DR. This suggestion is based on the findings that both atropine and mecamylamine antagonized the effects of APO, while carbachol at a high dose exerted an effect opposite to that of APO. Besides, pirenzepine and bicuculline at low doses also antagonized, whereas saclofen did not alter the influence of APO on 5‐HT in the striatum. Bicuculline at a higher dose enhanced tryptophan and 5‐HT measures by itself. None of the drugs studied had a significant effect on tryptophan, 5‐HT, or 5‐HIAA in the hippocampus. These results together suggest that DA, ACh, and GABA neurons are all involved in the actions of APO on 5‐HT, while the direct synaptic relationships among these neurotransmitters and the precise anatomical locus for these interactions to occur are still unknown. It is possible that APO, by inhibiting DA neuron firing in the substantia nigra and through the GABA disinhibition mechanism, therefore indirectly activates 5‐HT neurons in the DR and the striatum. While the above neuronal firing model well explains the elevation of 5‐HIAA, the simultaneous increases of tryptophan and 5‐HT, especially tryptophan, may be more readily explained by a mechanism of tryptophan uptake upon APO administration. Further anatomical, biochemical, and electrophysiological studies are ongoing to test this hypothesis and to clarify the circuit and the anatomical locus (loci) for t
ISSN:0887-4476
DOI:10.1002/syn.890100106
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1992
数据来源: WILEY
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6. |
Multiple heteroreceptors on limbic thalamic axons: M2acetylcholine, serotonn1B, β2‐adrenoceptors, μ‐opioid, and neurotensin |
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Synapse,
Volume 10,
Issue 1,
1992,
Page 44-53
Brent A. Vogt,
Peter B. Crino,
Eugene L. Jensen,
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摘要:
AbstractLigand binding to many transmitter receptors is much higher in layer Ia of rat posterior cingulate cortex than it is in other layer, and this is where most axons from the anterior thalamus terminate. The present study explores the possibility that a number of receptors may be expressed on axons from limbic thalamic nuclei that terminate in layer Ia. Unilateral thalamic lesions were placed in rats and, 2 weeks later, five ligand binding protocols, coverslip autoradiography, and single grain counting techniques were used to qunatify binding in control and ablated hemispheres. Binding to the following receptor subtypes was analyzed: M2acetylcholine,3H‐oxotremorine‐M, or3H‐AF‐DX 116 with 50 nM pirenzepine; serotonin1B,125I‐(−)‐cyanopindolol with 30 μM isoproterenol; β2‐adrenoceptors,125I‐(−)‐cyanopindolol with 1 μM serotonin and 10 μM atenolol; μ‐opioid,3H‐Tyr‐D‐Ala‐Gly‐MePhe‐Gly‐ol; neurotensin,3H‐neurotensin. Thalamic lesions reduced binding in two laminar patterns. In one pattern, there was a major reduction in binding in most superficial layers with that in layer Ia ranging from 50 to 70% for binding to M2muscarinic and serotonin1Breceptors. Binding to β2‐adrenoceptors was also reduced in most superficial layers but to a lesser extent. In the second pattern, reductions were limited to layer I with losses in layer Ia of 20–30% for μ‐opioid and neurotensin receptors. In no instance was layer Ia binding completely abolished (i.e., postlesion peaks remained).Since the transmitters for each of the five receptors analyzed in this study are not synthesized by anterior or laterodorsal thalamic neurons, these receptors are heteroreceptors. The greatest postlesion reduction in M2binding was for AF‐DX 116 and so most M2heteroreceptors are of the “cardiac” subtype. Finally, the diverse population of heteroreceptors on limbic thalamic axons provides for presynaptic modulation by a wide range of transmitter systems and suggests that thalamoco
ISSN:0887-4476
DOI:10.1002/syn.890100107
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1992
数据来源: WILEY
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7. |
Local application of bicuculline potentiates NMDA‐receptor‐mediated sensory responses of brain noradrenergic neurons |
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Synapse,
Volume 10,
Issue 1,
1992,
Page 54-61
Ramin Shiekhattar,
Gary Aston‐Jones,
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摘要:
AbstractDirect application of bicuculline methiodide (BIC) to noradrenergic locus coeruleus (LC) neurons potently enhanced their sensory responsiveness. This increased responsiveness was due to the long‐lasting expression of a new, N‐methyl‐D‐aspartate (NMDA) receptor‐mediated component of the synaptic response. This enhancement only occurred when a high stimulus intensity was used to induce the sensory response. A similar increase in responsiveness was observed with stimulation of the nucleus paragigantocellularis (PGi), one of the major direct afferents to LC. This action of BIC was neither mimicked by picrotoxin, penicillin, or the GABA‐B antagonist, 2‐hydroxysaclofen, nor by agents that directly depolarize LC neurons. In addition, the inverse agoinst of the benzodiazepine receptor, methyl‐6,7‐dimethoxy‐4‐ethyl‐β‐carboline‐3‐carboxylate (DMCM), did not mimic this effect of BIC. The BIC‐potentiated response component was eliminated by direct application of the neurotransmitter γ‐aminobutyric acid (GABA). These results indicate that BIC, acting at a possibly novel site, unmasks NMDA receptors that can be activated by sensory stimuli. This may reflect a mechanism whereby interactions between two major neurotransmitter systems, excitatory amino acids (EAAs) and GABA, potently modula
ISSN:0887-4476
DOI:10.1002/syn.890100108
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1992
数据来源: WILEY
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8. |
Activators of protein kinase C increase the phosphorylation of the synapsins at sites phosphorylated by cAMP‐dependent and Ca2+/calmodulin‐dependent protein kinases in the rat hippocampal slice |
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Synapse,
Volume 10,
Issue 1,
1992,
Page 62-70
Michael D. Browning,
Ellen M. Dudek,
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摘要:
AbstractPrevious studies have shown that activators of protein kinase C (C kinase) produce synaptic potentiation in the hippocampus. For example, the C kinase activator phorbol dibutyrate has been shown to increase transmitter release in the hippocampus. In addition, a role for C kinase in long‐term potentiation has been proposed. A common assumption in such studies has been that substrates for C kinase were responsible for producing these forms of synaptic potentiation. However, we have recently shown that phorbol dibutyrate increased the phosphorylation of synapsin II (formerly protein III, Browning et al., 1987) in chromaffin cells (Haycock et al., 1988). Synapsin II is a synaptic vesicle‐associated phosphoprotein that is a very poor substrate for C kinase but an excellent substrate for cAMP‐dependent and Ca2+/calmodulin‐dependent protein kinase. We felt, therefore, that activation of C kinase might lead to activation of a kinase cascade. Thus effects of C kinase activation might be produced via the phosphorylation of proteins that arenotsubstrates for C kinase. In this report we test the hypothesis that activators of C kinase increase the phosphorylation of synapsin II and an homologous protein synapsin I. Our data indicate that PdBu produced dose‐dependent increases in the phosphorylation of synapsin I and synapsin II. We also performed phospho‐site analysis of synapsin I using limited proteolysis. These studies indicated that PdBu increased the phosphorylation of multiple sites on synapsin I. These sites have previously been shown to be phosphorylated by both cAMP‐dependent protein kinase and the multifunctional Ca2+/calmodulin‐dependent protein kinase II. The ability of C kinase activators to produce a net increase in the phosphorylation state of these sites on synapsin was confirmed by a “back phosphorylation assay” with exogenous cAMP‐ and Ca2+/calmodulin‐dependent protein kinases. Previous studies have provided direct evidence that synapsin I regulates neurotransmitter release at the squid giant synapse and that this effect is controlled by phosphorylation of synapsin I by Ca2+/calmodulin‐dependent protein kinase II. Accordingly we hypothesize that the phosphorylation of synapsin I and the related protein, synapsin II, may play an important role in mediating the increased transmitter release elicited by activators of C kinase. Moreover, we suggest that the role played by C kinase in long‐term potentiation may involve, in part, the phosp
ISSN:0887-4476
DOI:10.1002/syn.890100109
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1992
数据来源: WILEY
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9. |
Differential effects of amfonelic acid on the haloperidol‐ and clozapine‐induced increase in extracellular dopac in the nucleus accumbens and the striatum |
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Synapse,
Volume 10,
Issue 1,
1992,
Page 71-78
Robert Rivest,
Charles A. Marsden,
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摘要:
AbstractThis study compares the effects of the nonamphetamine stimulant amfonelic acid on the increase in extracellular 3,4‐dihydroxyphenylacetic acid (DOPAC) induced by haloperidol and clozapine in the nucleus accumbens and the striatum of anaesthetized rats. DOPAC was simultaneously recorded in both regions using differential pulse voltammetry with electrically pretreated carbon fibre electrodes. Amfonelic acid (2.5 mg/kg s.c.) did not alter basal striatal DOPAC but produced a significant reduction in extracellular DOPAC in the nucleus accumbens. Haloperidol (1 mg/kg s.c.) increased extracellular DOPAC in both regions. When amfonelic acid was injected 5 min before haloperidol, the increase in DOPAC was potentiated in both the nucleus accumbens and the striatum but with a greater effect in the striatum. Clozapine (30 mg/kg i.p.) increased extracellular DOPAC in both regions, an effect partially attenuated by amfonelic acid in both regions but to a greater extent in the striatum. When ritanserin (5 mg/kg i.p.), a serotonergic antagonist (5‐HT‐2), was co‐administered with haloperidol, the potentiation by amfonelic acid of the increase in extracellular DOPAC induced by haloperidol was attenuated in both the nucleus accumbens and the striatum. The present results confirm that amfonelic acid can be used to discriminate neurochemically between haloperidol and clozapine in vivo. The effects of amfonelic acid on the neuroleptic‐induced changes in extracellular DOPAC were greater in the striatum than the nucleus accumbens. These results further demonstrate that both neuroleptics increase dopamine metabolism in the two brain regions but by different mechanisms, supporting the view that the regulation of dopamine metabolism differs in the two regions. Furthermore, the interaction between amfonelic acid and clozapine suggests that the increase in dopamine metabolism induced by the atypical neuroleptic results from the blockade of both dopaminergic and nondopaminergic receptors and may include the sertonergic (5‐HT
ISSN:0887-4476
DOI:10.1002/syn.890100110
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1992
数据来源: WILEY
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10. |
Reduced tyrosine hydroxylase immunoreactivity in locus coeruleus of suicide victims |
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Synapse,
Volume 10,
Issue 1,
1992,
Page 79-82
Anat Biegon,
Sheila Fieldust,
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摘要:
AbstractAntibodies against tyrosine hydroxylase (TH, the rate‐limiting enzyme in norepinephrine synthesis) and dopamine β‐hydroxylase (DBH, the last enzyme in the synthesis) were used for immunohistochemical staining of human brain locus coeruleus sections, obtained postmortem form suicide victims and matched controls. Stain density over individual cells was quantified by a computerized, video‐camera‐based image analysis system. Mean stain density for TH was significantly lower (by about 30%) in the locus coeruleus of suicide victims. There was no difference between suicides and controls in DBH immunoreactivity or in the number of TH immunoreactive cells. Reduced TH availability, either genetically or environmentally determined, may contribute to the noradrenergic insufficiency postulated to occur in depression and the increased β‐adrenergic receptor concentrations observed in prefrontal cortex of suic
ISSN:0887-4476
DOI:10.1002/syn.890100111
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1992
数据来源: WILEY
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