摘要:

AbstractRecent research has indicated that synaptic curvature is an important and potentially critical plastic feature of the synapse. Alterations in synaptic shape are related to synaptic function, being found both during maturation and in adulthood following neuronal activation. In this paper we review the evidence supporting synaptic shape as a plastic feature of synaptic structure. We also propose several mechanisms which might underlie these changes in shape. Finally, we suggest the possible functional role of alterations in synaptic curvature, including its potential in altering synaptic transmission efficacy.

ISSN:0887-4476    

DOI:10.1002/syn.890030102

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

年代:1989

数据来源: WILEY

摘要:

AbstractIn immunocytochemical studies, a polyclonal antiserotonin antibody was used to visualize fibers within the cingulate cortex of young and aged rhesus monkeys. Intricate and distinct patterns of serotoninergic processes were seen in anterior and posterior segments of cingulate cortex (Brodmann areas 24 and 23). In these regions of cortex, many multivaricose serotonin‐immunoreactive axonal swellings were identified, and some of these immunostained neurites were associated with deposits of amyloid. These observations suggest that serotoninergic processes are involved in the formation of senile plaques in neocortex of aged macaque

ISSN:0887-4476    

DOI:10.1002/syn.890030103

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

年代:1989

数据来源: WILEY

摘要:

AbstractRecent evidence demonstrates that controlled visual stimuli cause the generation, in the primary visual cortex of rhesus monkey cells, of large numbers of very precisely replicating copies of complex patterns of discharge consisting of three or more spikes, the patterns of which presumedly code for specific qualities of the stimuli presented. We present evidence that the copies of precisely replicating triplets of spikes, generally not exceeding 100 ms in duration, occur in close time proximity to many copies of highly precise “ghost” doublets. These doublets are defined as patterns consisting of two pulses, with precise separations in time, specifically those that would be generated if any one of the pulses making up a given replicating triplet were missing. In striking contrast, nonreplicating triplets (also present in these records)–that is, triplets made up of intervals that are not present in replicating triplet–arenotaccompanied by such ghost doublets. The persistence (memory) of capacity to produce such ghost doublets decays according to two independent kinetic rules. The first of these results in the disappearance of such doublets within about 0.1 s as measured by two independent methods, whereas the second disappears only after several minutes or longer. These results provide strong evidence consistent with the notion that at least some parts of the brain transmit, store representations of, and retrieve qualitative information through the use of a code consisting of specific patterns of nerve discharges

ISSN:0887-4476    

DOI:10.1002/syn.890030104

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

年代:1989

数据来源: WILEY

摘要:

AbstractSingle‐unit electrophysiological recording techniques were used to sample the basal activity of antidromically identified nigrostriatal and mesoaccumbens dopamine (NSDA and MADA, respectively) neurons and to examine the responsiveness of these cells to dopamine agonist‐induced inhibition of cell firing rate in either chloral hydrate‐anesthetized or paralyzed rats. Paralyzed rats exhibited a greater percentage of burst‐firing cells (69%) than did anesthetized animals (37%). Furthermore, paralyzed rats were less sensitive to the mixed D1/D2 DA receptor agonist apomorphine and the selective D2 DA receptor agonist quinpirole. However, significantly higher doses of d‐amphetamine were required in paralyzed animals only with respect to inhibiting MADA neurons. The abilities of apomorphine and quinpirole to inhibit NSDA cell firing were rate‐dependent in both anesthetized and paralyzed rats, whereas d‐amphetamine‐induced inhibition was rate dependent only in anesthetized animals. In contrast, apomorphine‐ and quinpirole‐induced inhibition of MADA neurons were rate‐dependent only in anesthetized rats, whereas d‐amphetamine‐induced inhibition was rate‐dependent only in paralyzed animals. These results suggest that general anesthesia exerts subtle effects on the basal activity and pharmacological responsiveness o

ISSN:0887-4476    

DOI:10.1002/syn.890030105

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

年代:1989

数据来源: WILEY

摘要:

AbstractWe previously found that quinolinic acid striatal excitotoxin lesions result in a relative sparing of somatostatin and neuropeptide Y neurons. In the present study we examined dose‐response effects of excitotoxins acting at the three subtypes of glutamate receptors: N‐methyl‐D‐aspartate (AA1), quisqualate (AA2), and kainic acid (AA3). Concentrations of both somatostatin‐like immunoreactivity (SLI) and neuropeptide a Y‐like immunoreactivity (NPYLI) were compared with those of substance P‐like immunoreactivity (SPLI) and GABA. Kainic acid (AA3), quisqualic acid (AA2), and AMPA (AA2) resulted in dose‐dependent reductions in all four neurochemical markers examined, while N‐methyl‐D,L‐aspartate (AA1) and quinolinic acid (AA1) resulted in relative sparing of SLI and NPYLI. At doses of each excitotoxin which resulted in comparable 50% reductions in both GABA and SPLI only N‐methyl‐D,L‐aspartate and quinolinic acid had no significant effect on concentrations of SLI and NPYLI. The relative sparing of somatostatin‐neuropeptide Y neurons was confirmed histologically by using histochemical staining for NADPH‐diaphorase neurons combined with either Nissl stains, or immunohistochemical staining for enkephalin. Lessions with N‐methyl‐D‐aspartate agonists resulted in preferential sparing of NADPH‐diaphorase neurons while these neurons were more vulnerable than other neurons to kainic acid or AMPA. Choline acetyltransferase neurons were relatively spared, as compared with other neurons, by agents acting at all three glutamate receptor subtypes. N‐methyl‐D,L‐aspartate lesions were blocked with MK‐801, while there was no effect on quisqualic acid or kainic acid lesions. The relative sparing of somatostatin‐neuropeptide Y neurons following striatal excitotoxin lesions with N‐methyl‐D‐aspartate (AA1) agonists probably reflects a paucity of AA1 receptors on these neurons. Since these neurons are also spared in Huntington's disease, excitotoxins acting at the N‐methyl‐D‐aspartate (AA1)

ISSN:0887-4476    

DOI:10.1002/syn.890030106

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe effects of cocaine on dopamine (DA) neurotransmission were evaluated by in vivo microdialysis in the striatum of halothane‐anesthetized rats. Intravenous cocaine produced a dose‐dependent, transient increase of the extracellular concentration of DA, with a peak response within 10 min and a return to control level by 30 min. The sharp DA response pattern was abolished in a calcium‐free environment, indicating that DA release enhanced by cocaine originates from a vesicular storage pool. Continuous administration of cocaine (via the perfusion medium) directly into the nigrostriatal terminal region also produced a dose‐dependent increase in DA release. Low concentrations (10−5M and 10−6M) of cocaine maintained DA at a constant stable level, consistent with the effects observed after potent DA uptake inhibitory agents (e.g., nomifensine and Lu19005). However, continuous exposure to high concentrations (<10−4M) induced a transient elevation of DA within 20 min, following which DA decreased to a stable but high level; this decrease might reflect tolerance to the effect of cocaine. Administration of cocaine (10−3M) into the substantia nigra did not change striatal DA release. The local striatal action of cocaine was less potent than amphetamine in elevating DA overflow and in its effect on DA metabolism. These findings suggest that the fast transient enhancement of DA by intravenous cocaine is most likely a consequence of the transient presence of cocaine in the terminal region, correlating with the well‐known rapid pharmacokinetic and behavioral as

ISSN:0887-4476    

DOI:10.1002/syn.890030107

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

年代:1989

数据来源: WILEY

摘要:

AbstractBrain reward systems are thought to be involved in the reinforcing effect of both cocaine and opiates. In vitro receptor autoradiography was used to determine the effect of chronic, continuous cocaine exposure of 2 weeks duration on [3H]naloxone binding in various regions of rat brain. Although cocaine action in the central nervous system is usually associated with altered dopamine function, we observed that opiate receptor density as labeled by [3H]naloxone was altered by chronic cocaine exposure in critical brain reward regions, including the nucleus accumbens, ventral pallidum, and lateral hypothalamus. Endogenous opioid activity at opiate receptors in these critical regions may be associated with the reinforcement induced by both cocaine and opiates.

ISSN:0887-4476    

DOI:10.1002/syn.890030108

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

年代:1989

数据来源: WILEY

摘要:

AbstractHigh‐affinity, specific3H‐5‐hydroxytryptamine (5‐HT) binding was analyzed in membrane homogenates of human frontal cortex, caudate, and globus pallidus. 5‐HT1Aand 5‐HT1Cbinding sites were pharmacologically blocked using 100 nM 8‐hydroxy‐N,N‐dipropyl‐2‐aminotetralin (8‐OH‐DPAT) and 100 nM mesulergine, respectively. The majority of 5‐HT1sites remained in each of the three brain regions under these conditions. The pattern of nucleotide interactions with these binding sites (GppNHp = GTP = GDP>GMP = adenine nucleotides) suggests a possible linkage to a G protein. RU 24969 competition studies confirmed the absence of 5‐HT1Bbinding sites in human cortex, caudate, and globus pallidus. Drug interactions with putative 5‐HT1Dbinding sites in bovine caudate membranes correlated significantly with their affinities for human membrane recognition sites labeled by3H‐5‐HT in the presence of 100 nM 8‐OH‐DPAT + 100 nM mesulergine. We conclude that the majority of3H‐5‐HT‐labeled recognition sites in human cortex, caudate, and

ISSN:0887-4476    

DOI:10.1002/syn.890030109

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

年代:1989

数据来源: WILEY

摘要:

AbstractTo examine mechanisms that might be responsible for limiting transmission at excitatory synapses in hippocampus, we analyzed the relationship between extracellular calcium concentrations (1‐6 mM) and postsynaptic responses in field CA1 of hippocampal slices using low stimulation intensities and a paired‐pulse paradigm. Three effects were observedOne, the relationship between calcium levels and the slope (or amplitude) of the postsynaptic response was described by a sigmoidal function with an asymptote at about 4 mM. Double reciprocal pilots relating calcium concentration to the initial slope of EPSPs provided evidence for the cooperativity expected between calcium ions and transmitter release.Two, both the rise time and half‐decay time of the postsynaptic responses were reduced with increasing calcium concentrations. These effects of calcium were more pronounced on the first response elicited by paired‐pulse stimulation and were considerably attenuated by 2 μM bicuculline, indicating that feed‐forward inhibition was positively related to calcium concentration and differentially activated by repetitive stimulation. However, inhibition was not responsible for the asymptotic relationship observed between calcium and response size.Three, while increasing the calcium concentration beyond 4 mM did not further affect the initial slope of excitatory postsynaptic potentials (EPSPs), paired‐pulse facilitation and 4‐aminopyridine were still effective in increasing response size. These results suggest (1)that neither the number of postsynaptic receptors nor the number of transmitter quanta available for release were limiting transmission as a function of the calcium concentration; and (2)that calcium entry into presynaptic terminals was likely to represent the limiting step under the c

ISSN:0887-4476    

DOI:10.1002/syn.890030110

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe effects of chronic blockade of D‐1, D‐2, or both subtypes of dopamine receptors on the densities and properties of the D‐1 and D‐2 subtypes of dopamine receptors were measured in rat brain. Animals were treated with 14 daily injections (i.p.) of the D‐1‐selective antagonist SCH‐23390, the D‐2‐selective antagonist sulpiride, the nonselective antagonist fluphenazine, or vehicle. Serial 32‐μm horizontal sections that included the caudate putamen were cut and alternately assigned to assays for D‐1 or D‐2 receptors. D‐1 receptors were labeled with3H‐SKF‐83566 or3H‐SCH‐23390, and D‐2 receptors were labeled with3H‐spiroperidol. Scatchard analysis was performed on the saturation data measured in the head of the caudate putamen to obtain estimates of receptor density. As expected, administration of the D‐1‐selective ligand SCH‐23390 resulted in an increase in the density of D‐1 receptors by approximately 47% and had no significant effect on the density of D‐2 receptors. Similarly, administration of the D‐2‐selective ligand sulpiride resulted in an increase in the density of D‐2 receptors by 25% and had no significant effect on the density of D‐1 receptors. Thus the subtypes of dopamine receptors appear to be independently regulated after selective blockade. In contrast to the effects observed with selective antagonists, the results obtained with fluphenazine were more complex. Administration of the relatively nonselective antagonist fluphenazine resulted in an increase in the density of D‐2 receptors by 51% but had no significant effect on the density of D‐1 receptors. One explanation for this result is that up‐regulation of D‐2 receptors inhibits the regulation of D‐1 receptors, suggesting that the regulation of subtypes of dopamine receptors is not entirely independent. In support of this hypothesis, coadministration of sulpiride with SCH‐23390 attenuated the ability of SCH‐23390 to up‐regulate D‐1 receptors. To determine whether this phenomenon is observed in other brain regions, a second group of animals was chronically treated with selective and nonselective antagonists as described above, and coronal sections were cut at multiple levels of the brain. Receptors were labeled with a single concentration of either3H‐SCH‐23390 or3H‐spiroperidol, and the binding of the radioligands in 19 discrete brain regions was measured. The effects of these treatments on D‐1 and D‐2 receptors in

ISSN:0887-4476    

DOI:10.1002/syn.890030111

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

年代:1989

数据来源: WILEY