bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in the structure of synaptic junctions during climbing fiber synaptogenesis
Authors: Landis Dennis M. D. , Payne H. Ross , Weinstein Lori A. 
Published: January 2005

AbstractSynaptogenesis between climbing fiber axons and Purkinje cells involves both an orderly translocation of synaptic junctions over the Purkinje cell surface and an elimination of all but one innervating axon. We used thin‐section and freeze‐fracture electron microscopic techniques to study structural changes in synaptic junctions during this interval of synapse translocation and elimination. In freeze‐fractured preparations, virtually all climbing fiber synaptic junctions with the perisomatic processes and somatic spines lacked the particle aggregates that characterized the extracellular half of the postsynaptic membrane of mature synaptic junctions with dendritic spines. Some climbing fiber junctions with the dendritic shaft in the second postnatal week were associated with such aggregates, despite the fact that these junctions are transient. Thus, during the interval when Purkinje cells initially were innervated by multiple climbing fibers, and subsequently denervated of all but one climbing fiber afferent per cell, only a few of the transient synaptic junctions on the cell body and proximal dendrites have associated particles. The presence of a particle aggregate at a synaptic junction does not appear to be correlated with the permanence of that junction and probably is not correlated with the capacity to support synaptic transmission. The particle aggregates might be indicative of relatively long‐lived junctions, or might occur only at junctions formed by the climbing fiber that will persist in synaptic contact with the mature Purkinje cell.
Excitatory amino acid treatment of the ventromedial globus pallidus enhances dopamine utilization in the prefrontal cortex of the rat via the thalamic mediodorsal nucleus
Authors: Jones M. W. , Kilpatrick I. C. , Phillipson O. T. 
Published: January 2005

AbstractInfusion of a low dose (5 μM) of the cell‐selective chemical excitant quisqualic acid (QUIS) into rostral ventromedial globus pallidus (GP) had no immediate effect on DA utilization (assessed as [DOPAC]:[DA] and [HVA]:[DA] ratios) in either the medial bank of the prefrontal cortex (FCx) or the agranular insular cortex (AgCx). In contrast, a larger dose (630 μM) of another excitant sodium ibotenate (IBO) produced an immediate bilaterally symmetrical increase in both indices of DA utilization in FCx. There was also a marked trend towards a bilateral increase in these indices of DA utilization in AgCx. In order to determine whether these effects on cortical DA utilization are mediated by a direct cortical route or via the thalamic mediodorsal nucleus (lateral division, MDL), infusions of IBO into GP were repeated in animals with a 1‐week‐old N‐methyl‐D‐aspartate lesion of MDL. The increase in DA utilization of FCx following infusion of IBO into GP was abolished, although the trend towards increased DA utilization in AgCx was still maintained. Since MDL innervates FCx but not AgCx and since we have previously shown that MDL lesions alone have no effect on DA utilization in either cortical region, the present results suggest that the changes in cortical DA utilization are probably mediated via MD. Thus in addition to the well‐documented control exerted by the thalamus over brain DA function, this has now been extended in the present study to include GP, which projects both directly and indirectly to the thalamus.
1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine‐Induced neurotoxicity in the rat: Characterization and age‐dependent effects
Authors: Jarvis Michael F. , Wagner George C. 
Published: January 2005

Abstract1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is a potent dopaminergic toxin that has been found to produce Parkinson's disease‐like symptoms in humans and monkeys. The neurotoxic effects of MPTP appear to be reduced in rodents where multiple dosing procedures are required to demonstrate long‐lasting neuronal deficits. In the present study, the neurotoxic effects of MPTP were further characterized in the rat. Following the repeated administration of MPTP, pronounced (60–80%) and dose‐dependent depletions of striatal dopamine and serotonin concentrations were found in the rat brain. Time‐course studies revealed that while striatal dopamine concentrations remained consistently reduced for at least 8 weeks following MPTP treatment, striatal serotonin depletions as well as MPTP‐induced monoamine depletions in other brain regions were transient in nature. Pretreatment with the MAO‐B inhibitor pargyline afforded a selective and complete protection of striatal dopamine levels without significantly affecting MPTP‐induced striatal serotonin depletions. Similarly, treatment with ascorbic acid was found to selectively attenuate MPTP‐induced dopamine depletions in rats. The neurotoxic effects of MPTP were also found to increase in the developing rat. No significant brain monoamine depletions were observed in neonatal rats following the repeated administration of MPTP. However, MPTP‐induced neurotoxicity progressively increased in older rats. The present results indicate that when appropriate treatment procedures are used, a pronounced, selective, age‐dependent, and long‐lasting MPTP‐induced reduction in striatal dopamine concentrations can be observed in the rat brain. The present results are discussed in references to the putative mechanisms and species differences of MPTP‐induced neurotoxicity.
Pargyline‐Sensitive selective accumulation of a radiolabeled MPTP analog in the primate cerebral cortex and basal ganglia
Authors: Efange S. M. N. , Kung H. F. , Mash D. C. , Jabir M. , Billings J. , Pablo J. , Dutta A. , Freshler A. 
Published: January 2005

AbstractThe distribution of radioiodinated N‐methyl‐4‐(4‐hyroxy‐3‐iodobenzyl)‐1,2,3,6‐tetrahydropyridine (MHTP), an analog of the reportedly nontoxic N‐methyl‐4‐benzyl‐1,2,3,6‐tetrahydropyridine, (4‐homo‐MPTP), has been studied in the primate. [123I]‐MHTP‐derived radioactivity exhibited a progressive accumulation and prolonged retention within the primateeye. Following injection, [123I]MHTP rapidly accumulated within the primate brain and was subssequently oxidized to a radiolabeled metabolite. The half‐life of [123I]MHTP‐derived radioactivity within the primate brain was 50 min. The highest concentrations of radioactivity were found in the caudate‐putamen and the frontal, temproal and cingulate cortices; the substantia nigra and inferior olivary nucleus were labeled with medium intensity. Very low concentrations of radiolabel were detected in the cerebellum and white matter, Selective accumulation of [125I]MHTP‐derived radioactivity within these structures was blocked by pretreatment with pargyline, suggesting that nonoamine oxidase B is involved in the bioactivation of radioiodinated MHTP.
Statistical analysis of dose‐response curves in extracellular electrophysiological studies of single neurons
Authors: Pitts David K. , Kelland Mark D. , Shen Roh‐Yu , Freeman Arthur S. , Chiodo Louis A. 
Published: January 2005

AbstractThe application of polynomial regression and the analysis of covariance (ANCOVA) to dose‐response (DR) data derived from extracellular electrophysiological studies of midbrain dopamine neurons and noradrenergic locus coeruleus neurons in vivo is demonstrated and discussed. Third‐order polyomial regression was found to be a better method for estimating ED50 values than probit analysis or linear regression. ANCOVA provides a more powerful statistical method than ANOVA for detecting significant differences in ED50 values or DR curves when a confounding variable such as basal discharge rate is present. The methods of analysis presented herein should be useful in the analysis of other types of neurons in electrophysiol studies.
Regultion of adrenergic receptors in intraocular hippocampal transplants: Role of Noradrenergic Innervation
Authors: Mynlieff Michelle , Curella Pamela , Zahniser Nancy R. , Gerhardt Greg A. , Seiger Ake , Dunwiddie Thomas V. 
Published: January 2005

AbstractHippocampal tissue transplanted into the anterior chamber of the eye offers a unique system in which development can be studied in the absensce of the noradrenergic innervation. This system was used to determine the extent to which noradrenergic innervation regulates the developement of adrenergic receptors. In addition to examining single denervated transplates, transplants grown with innervation from the superior cervical ganglia of the host rat or from locus coeruleus cotransplants were also examined to determine whether the source of norepinephrine and extent of innervation in oculo regulate the developement and density of adrenergic receptors. In vitro autoradiographic analysis of ligand binding to both α1‐ and β‐adrenergic receptors. In vitro autoradiographic analysis of ligand binding to both α1‐and β‐adrenergic receptors with 125‐I‐BE2254 and 125I‐pindolol, respectively, was used to charcterize aderenergic receptors in the intraocular transplants. Quantitative analysis of the receptors showed and up‐regulation of both α1‐ and β‐adrenergic receptors in tissue grown in the absence of norepinephrine, but in general there was not a high degree of correlation between norepinephrine content and receptor density. Although high‐performance liquid chromatography (HPLC) analysis of catecholamines revealed higher than normal amounts of norepinephrine in hippocampal transplants innervated by the superior cervical ganglia or a locus coeruleus cotransplant, the density of α1‐ and βreceptors was quite comparable with values found in the literature for normal adult hippocampus. These results suggest that the relationship between receptor number and density of innervation may differ significantly from what is observed in response to pharmacological manipultion of norepinephrne systems in the adult brain.
Electrophysiological identification of a pathway from the septal area to the medial amygdala: Sensitivity to estrogen and luteinzing hormone‐releasing hormone
Authors: Dudley Carol A. , Lee Yong , Moss Robert L. 
Published: January 2005

AbstractMedial amygdala neurons responsive to electrical stimulationof the medial septal area were electrophysiologically identified in ovariectomized, urethane‐anesthetized female rats. Peristimulus time histograms were collected and used to define the orthodromic response. The action of iontophoretically applied luteinzing hormone‐releasing hormone (LHRH) and an LHRH fragment, Ac‐LHRH5–10, on the activity of were identified as orthodromically responsive. Three types of orthodromic responses were observed: excitatory, inhibitory, and complex. Priming the animals with 5 μg estradiol benzoate (EB) 48 hr prior to recording had no effect on the overall number of neurons responding to septal area stimulation, but EB priming did significantly reduce the percentage of orthodromically excited neurons. The firing rate of the majority of amygdala neurons responsive to septal area stimularion was not affected by iontophoretically applied LHRH (59 of 76) or LHRH fragment (41 of 65). In some cases, application of LHRH (10 of 76) or Ac‐LHRH5‐10 (12 of 55) produced a change in neuronal firing that was similar in direction to the orthodromically evoked response. When applied during the collection of peristimulus time histograms, both peptides were also able to modulate the orthodromically evoked response (five of 18 cells tested with LHRH and three of 14 cells tesed with Ac‐LHRH5‐10). The results demonstrate a large projection from the septal area to the amygdala, one component of which is altered by estrogen priming. The findings suggest that LHRH released from septal neurons may act as a neurotransmitter and a neuromodulator in the medial amygdala; however, the large number of neurons unaffected by the decapeptide indicates that the role of LHRH at this synapse is subservient to that of another tranmitter (s).
Identification of a subpopulation of neuropeptide Y‐containing locus coeruleus neurons that project to the entorhinal cortex
Authors: Wilcox Barbara J. , Unnerstall James R. 
Published: January 2005

AbstractA Fundamental question important to the undersanding of the neuro‐chemical organization of the central nervous system focuses on the relationships between the differential phenotypic expression of multiple neurotransmitter markers in individual neuronal populations and the factors that regulate their expression. The first approach in studying this phenomenon is the determination of specifcic relationships between neuro‐chemically distinct neuronal subpopulations and their efferent targets. The pontine nucleus locus coeruleus (LC) provides a useful model for adressing this question since the projections of LC neurons are topographically organized and several neuropeptides are expressed along with noradrenergic markers in subsets of these neurons. In these studies, we have focused on defining the efferent targets of LC neurons that contain neuropeptide tyrosine (NPY)‐like immunoreactivity. The has been accomplished by injecting the retrograde fluorescent tracer fluorogold into specifec cortical and hippocampal targets in adult rats and identifying the proportion of retrogradely labeled LC neurons that are positive for NPY‐like immunoreactivity. In agreement with other investgators, no preferential cortical projections of NPY‐positive LC neurons were observed. However, when fluorogold injections included or were limited to the entorhinal cortex, a discrete cluster of round or ovoid neurons in the dorsomedial portion of the LC approximately 9.8 mm posterior to bregma were found to contain NPY‐like immunoreactivity. This observation demonstrates that some topographic organization of NPY‐containing LC neurons does exist. In fact, these data indicate that morphologic and topographic organisation exists even within neurochemically distinct subsets of neuronal populations.
Effect of short‐term serotonin depletion on the efficacy of serotonin neurotransmission: Electrophysiological Studies in the Rat central Nervous System
Authors: Chaput Yves , Lesieur Philippe , de Montigny Claude 
Published: January 2005

AbstractThe effects of short‐term serotonin (5‐HT) depletion by p‐chlorophenylalanine (PCPA) on the firing activity of dorsal raphe nucleus 5‐HT neurons, on the responsiveness of dorsal hippocampus pyramidal neurons to microiontophoretically applied 5‐HT and on the efficacy of the electrical stimulation of the ascending 5‐HT pathway in suppressing the firing activity of CA3 dorsal hippocampus pyramidal neurons were assessed in chloral hydrate‐anesthetized rats. PCPA (250 mg/kg/day i.p. for 2 days) reduced the 5‐HT content of the dorsal hippocampus by 90%. However, the number of spontaneously active 5‐HT neurons per microelectrode trajectory through the dorsal raphe or their average rate of firing was unaltered. The effect of afferent 5‐HT pathway stimulation was reduced in only 40% of treated rats, whereas the sensitivity of CA3 pyramidal neurons to microiontophoretic 5‐HT was not modified. The function of the terminal 5‐HT autoreceptor was assessed using methiothepin, an autoreceptor antagonist. Methiothepin (1 mg/kg, i.v.) significantly enhanced the efficacy of the stimulation in PCPA‐treated rats, although the degree of enhancement was much less than in controls. A greater reduction of the effectiveness of the stimulaiton was obtained by increasing the dose of PCPA (350 mg/kg/day i.p. for 2 days). This regimen reduced the 5‐HT content of the dorsal hippocampus by 95%. In these rats, the sensitivity of the terminal 5‐HT autoreceptor was assessed by increasing the frequency of the stimulation from 1 to 5 Hz. This procedure reduced to a similar extent the efficacy of the stimulation in treated and control rats, suggesting that the reduced effectiveness of the stimulation in treated and control rats, suggesting that the reduced effectiveness of methiothepin in enhancing 5‐HT synaptic transmission in PCPA‐treated rats is due to a lower degree of activation of the terminal 5‐HT autoreceptor. The present results showing that the 350 mg/kg/day regimen of PCPA, but not the 250 mg/kg/day regimen, reduced the efficacy of the stimulation of the ascending 5‐HT pathway suggest that a greater than 90% depletion is required to affect 5‐HT neurotransmission significantly. The reduced level of activation of terminal 5‐HT autoreceptors in rats treated with the lower dose of PCPA may facilitate the release of the remaining 5‐HT per stimulation‐triggered action potential, ensuring a virtually unaltered synaptic efficacy.
Tyrosine hydroxylase and galanin mRNA levels in locus coeruleus neurons are increased following reserpine administration
Authors: Austin Mark C. , Cottingham Sandra L. , Paul Steven M. , Crawley Jacqueline N. 
Published: January 2005

AbstractThe neuropeptide galanin coexists in 80–90% of the norepinephrine‐containing neurons in the locus coeruleus. In situ hybridization histochemistry was used to examine the effects of reserpine treatment or swim stress on tyrosine hydroxylase and galanin mRNA concentrations in locus coeruleus neurons. Reserpine administration significantly increased tyrosine hydroxylae and galanin mRNA levels in the locus coeruleus. The reserpine‐induced increase in tyrosine hydroxylase mRNA was significantly correlated with the reserpine‐induced increase in galanin mRNA. Three consecutive days of swim stress did not significantly alter either tyrosine hydroxylase or galanin mRNA concentration in the locus coeruleus. These data suggest that both tyrosine hydroxylase and galanin gene expression in locus coeruleus neurons may be regulated by a reserpine‐sensitive mechanism.
Transduction of the modulatory effect of catecholamines at the mammalian motor neuron terminal
Authors: Chen Hsinyo , Dryden William F. , Singh Yadhu N. 
Published: January 2005

AbstractMEPP frequency (f) was measured in mouse phrenic nerve hemidialphragm preprations during exposure to adrenoceptor agonist and antagonist drugs. Epinehprine, norepinephrine (NE), and phenylephrine caused a concentration‐dependent increase in frequency that was blocked by prazosin but yohimbine or nadolol. Isoproterenol had no effect on MEPP(f). The response to NE was not affected by prior incubatin of the tissues with pretussis toxin. The response was, however, reduced or abolished by prior exposure to drugs, the actions of which include protein kinase inhibition, and also to a calmodulin inhibitory concentration of W‐7. H‐7, an inhibitor of protein kinase C and of cyclic nucleotide‐dependent kinases, was ineffective. The response to NE was enahanced by 10 mM Li+. The data indicate the existence of a presynaptic α1‐adrenoceptor in the motor neuron terminal and suggest that modulation of transmitter release might be mediated by inositol triphosphate liberation, Ca2+ release into the cytosol and activation of a clamodulin‐dependent system.
The contribution of endogenous benzodiazepine receptor ligands to the pathogenesis of hepatic encephalopathy
Authors: Basile Anthony S. 
Published: January 2005

AbstractThe involment of the γ‐aminobutyric acidA (GABAA) receptor complex in the pathogenesis of hepatic encephalopathy (HE) was examined in galactosaminetreated rabbits with HE caused by fulminant hepatic failure. Radioligand binding to the constituent components of the GABAA receptor complex was unchanged in rabbits with HE. However, Partially purified extracts from encephalopathic rabbit brain were approximately three times more potent in inhibiting [3H] Ro 15‐1788 binding to benzodiazepine (BZ) receptors than extracts from control rabbits. The inhibition of radioligand binding to the BZ receptor produced by these extracts was competitive and reversible and was significantly enhanced by GABA. Further purification of these extracts by high‐performance liquid chromatography (HPLC) indicated that the inhibitory activity was localized in several peaks, some of which has retention times corresponding to 1,4‐benzodiazepine standards. The presence of diazepam in these extracts was confirmed using mass spectroscopy. Both mass spectoroscopic and radiametric techniques demonstrated that the concentration of diazepam in brain exstracts from encephalopathic rabbits was approximately 4 time greater than control extracts. These findings link the presence of BZ receptor agonists to the development of a neuropathological condition, therby providing a rational basis for the use of BZ receptor antagonists in the management of HE in man.
Excitatory amino acid antagonists protect mice against MPP+ seizures
Authors: Turski Lechoslaw , Stephens David N. 
Published: January 2005

AbstractAdminstration of 1‐methyl‐4‐phenyl‐pyridinium ion (MPP+) into the lateral ventricle of mice induced clonic convulsions and lethality in a dose‐ and age‐dependent manner. MPP+ failed to induce seizures in 4‐day‐old mice, and the convulsant response to MPP+ was enhanced in aged mice. The seizures triggered by MPP+ in adult mice were blocked by coadministration of L‐glutamate antagonists active at kainate/AMPA receptors such as α‐D‐glutamylaminomethylsulphonate and 2,3‐dihydroxy‐6‐nitro‐7‐sulphamoyl‐benzo[f]quinoxaline. The N‐methyl‐D‐asparate (NMDA) antagonist 2‐amino‐7‐phosphonoheptanoate, but not kynurenate, also protected mice against MPP+ convulsions. Similarly, the benzodiazepine midazolam and the adenosine A1 agonist 2‐chloroadenosine, but not antiepileptic drugs such as phenobarbital, trimethadione, ethosuximide, or acetazolamide, showed a protective efficacy against seizures. Additionally, the excitatory amino acid antagonists as well as phenobarbital, midazolam and 2‐chloradenosine protected mice against MPP+ lethality. These data suggest that convulsant action of MPP+ and its lethality in rodents may be mediated by excitatory amino acids.