bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct demonstration of interactions between substance P immunoreactive terminals and tyrosine hydroxylase immunoreactive neurons in the substantia nigra of the rat: An ultrastructural study
Authors: Mahalik Thomas J. 
Published: January 2005

AbstractThe results of many anatomical, physiological, and pharmacological studies suggest that substance P‐containing neurons of the striatum project to the substantia nigra, and that substance P influences the activity of dopaminergic nigrostriatal neurons. The purpose of the present ultrastructural study was to employ dual immunocytochemical labeling to determine the morphological basis for the observed actions of substance P on nigral dopaminergic neurons.Substance P‐like and tyrosine hydroxylase‐like immunoreactivities were localized simultaneously at the ultrastructural level in the substantia nigra of the rat. A double label method was utilized which relied on a combination of the peroxidase‐antiperoxidase method (Sternberger, 1979) for substance P, and immunogold or silver enhanced immunogold labeling for tyrosine hydroxylase.The present results indicate that tyrosine hydroxylase immunoreactive (THLI) dendrites in the substantia nigra receive synaptic input from terminals exhibiting substance P‐like immunoreactivity. These findings support the idea that substance P is a major neurotransmitter in the striatonigral loop, and suggest that striatal substance P neurons act directly upon nigral dopaminergic cells.
Single Ca2+ entry and transmitter release systems at the neuromuscular synapse
Authors: Guan Y.‐Y. , Quastel D. M. J. , Saint D. A. 
Published: January 2005

AbstractThe possibility that there exists more than one voltage‐gated Ca2+ channel system subserving quantal release of neurotransmitter at nerve endings was examined by measuring the sensitivity of quantal release to agents that block Ca2+ or Ba2+ entry, namely Cd2+, Mg2+, neomycin, and bekanamycin. The results show equal effectiveness vs. release evoked by presynaptic action potentials, brief intense presynaptic depolarizations, or prolonged relatively mild depolarizations, from which it is concluded that the same channel system is involved in each case. In the presence of Ba2+ and no Ca2+ there occur essentially normal (but small) endplate potentials (epps), while in the presence of Ba2+ epp amplitude and frequency of miniature epps co‐modulate with stimulation frequency in a manner which corresponds to a residual Ba2+ model for augmentation. It is therefore also concluded that a single transmitter release system is responsible for normal phasic release and the asynchronous release that is mediated by Ba2+.
Immunocytochemical evidence for substance P and serotonin input to medullary bulbospinal adrenergic neurons
Authors: Nicholas Anthony P. , Hancock Michael B. 
Published: January 2005

AbstractUsing two‐color immunoperoxidase staining combined with the retrograde transport of horseradish peroxidase injected into the rostral thoracic spinal cord, substance P‐immunoreactive (SPI) and serotonin‐immunoreactive (5HTI) variocosities have been observed in contiguity with medullary bulbospinal phenylethanolamine N‐methyl transferase‐immunoreactive (PNMTI) neurons of the C1, C2, and C3 cell groups. Since PNMTI terminals in the spinal cord are concentrated among sympathetic preganglionic neurons (SPGN) in the intermediolateral cell column, the close anatomical associations shown in the present study indicate that substance P‐ and serotonin‐containing pathways in the medulla likely affect activity of SPGN via adrenergic bulbospinal neurons.
Physiological correlates of responses to gamma‐aminobutyric acid (GABA) recorded from rat visual cortical neurons in vitro
Authors: Scharfman Helen E. , Sarvey John M. 
Published: January 2005

AbstractResponses to focal application of gamma‐aminobutyric acid (GABA) were compared to synaptic potentials elicited by afferent stimulation of rat visual cortical neurons, using a slice preparation and conventional intracellular recording techniques. GABA produced three types of responses: a brief hyperpolarization (mean reversal potential, −72 mV), brief depolarization (mean reversal potential, −50 mV), or a prolonged hyperpolarization (mean reversal potential, −80 mV). Synaptic potentials included simple or complex EPSPs and EPSPs followed by mono‐ or biphasic IPSPs. A comparison of the characteristics of the GABA responses and synaptic potentials indicated that GABA may mediate both phases of the IPSP in these cells. Our results suggest that despite differences in the circuitry of the visual cortex as opposed to other neocortical and allocortical (hippocampal) areas (Mountcastle and Poggio, 1968; Colonnier and Rossignol, 1969; Creutzfeldt, 1978; Kuhlenbeck, 1978), the inhibitory control of cortical pyramidal and nonpyramidal neurons by GABA is quite similar.
Changes in miniature end‐plate currents due to high potassium and calcium at the frog neuromuscular junction
Authors: Glavinovic M. I. 
Published: January 2005

AbstractElevation of extracellular potassium concentration ([K+]0) in cutaneous pectoris neuromuscular junction from 2 to 20 mM slowly increased the variability of the amplitudes of miniature end‐plate currents (AMEPC‐s), (coefficient of variation of AMEPC‐s increased by 73%). Mean AMEPC‐s, however, decreased but not markedly (by 14%). Comparable MEPC changes were observed when [K+] was raised in the presence of choline chloride (50 μM), arguing that MEPC changes were not primarily due to a lower and less uniform vesicular filling. Channel kinetics were not altered by high [K+]O, since the time constant of decay of miniature end‐plate currents (TMEPC‐s) did not change. Acetylcholine clearance from the synaptic cleft, however, appeared to be faster in high [K+ O since with cholinesterase blocked throughout, TMEPC‐s were shortened. The changes of spontaneous quantal discharge induced by high [K+]0] can be almost entirely explained by altered spatial distribution of vesicular release if, as recent reports suggest, at high [K+],0, exocytosis appears randomly not only at but also in between the active zones. However, relatively greater frequency of large MEPCs suggests that in high [K+]0 some, and possibly all, quanta are filled above normal levels.High [Ca2+]0 appears to counteract, although not always completely, all changes in spontaneous quantal secretion induced by high [K+]0. It is possible that high [Ca2+]0 reverses the changes in the spatial distribution of vesicular release induced by high [K+]0. However, high [Ca2+]0 also leads to other pre‐ and postsynaptic changes.
Adaptive changes of β‐adrenergic receptors after neonatal locus coeruleus lesion: Regulation of serotoninergic unit activity
Authors: Lanfumey Laurence , Adrien Joëlle 
Published: January 2005

AbstractSpontaneous activity of 5‐hydroxytryptamine (5‐HT) neurons in the dorsal raphe nucleus (DRN) was recorded in adult rats that had undergone a bilateral locus coeruleus (LC) lesion during the neonatal period. The susceptibility of this neuronal firing to β‐adrenergic manipulation was tested. Microiontophoretic application of the β‐blockers d,l‐propranolol and acebutolol inhibited the firing of DRN cells in lesioned rats but not in control animals. This effect was specific to β‐receptors since the effects of pharmacological manipulation of other receptors—5‐HT, γ‐aminobutyric acid (GABA), γ‐adrenoceptors— were identical in lesioned and control animals. The present data demonstrate that a neonatal noradrenergic lesion allowed the persistence of a β‐regulation of DRN neuronal firing, which in young rats is normally only transient.
Presence of ghost doublets of coded neuronal patterns: Relation to synaptic memory storage
Authors: Strehler Bernard L. , Lestienne Remy 
Published: January 2005

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–are not accompanied 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 in time.
Modelling afferent connectivity, postsynaptic plasticity, and signal discrimination
Authors: Chover Joshua 
Published: January 2005

AbstractWe model a small system of hypothetical neurons having ongoing afferent input (“stimulus”) short‐term refraction/inhibition, and brief‐latency intercellular excitatory feedback loops. We incorporate postsynaptic plasticity: synapses onto a given cell are grouped into dendritic “neighborhoods” wherein sufficiently large local postsynaptic potentials sums cause proportional changes in local synaptic efficacy. The efficacies record multiple cell‐to‐cell and time‐to‐time correlations. The efficacy patterns fall into several classes, for each of which there is a stereotypical relationship leading from “steady‐state” stimuli to corresponding sets of possible “responses” (periodic firing patterns). We examine the system's ability to discriminate between stimuli via firing patterns and to retain information during change of efficacies. There is an optimal region for efficacy configurations inside of which discrimination is good and outside of which the system can be inactive, particularly forgetful, of perseverative. We find that stimulus discrimination is enhanced by divergence and convergence in the pattern of afferent input. Perseverative firing patterns, invoked or suppressed by cotransmitters, can play a role in associative activities of the network.
Review: Cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: A novel experimental model of intractable epilepsy
Authors: Turski Lechoslaw , Ikonomidou Chrysanthy , Turski Waldemar A. , Bortolotto Zuner A. , Cavalheiro Esper A. 
Published: January 2005

AbstractHigh‐dose treatment with pilocarpine hydrochloride, a cholinergic muscarinic agonist, induces seizures in rodents following systemic or intracerebral administration. Pilocarpine seizures are characterized by a sequential development of behavioral patterns and electrographic activity. Hypoactivity, tremor, scratching, head bobbing, and myoclonic movements of the limbs progress to recurrent myoclonic convulsions with rearing, salivation, and falling, and status epilepticus. The sustained convulsions induced by pilocarpine are followed by widespread damage to the forebrain. The amygdala, thalamus, olfactory cortex, hippocampus, neocortex, and substantia nigra are the most sensitive regions to epilepsy‐related damage following convulsions produced by pilocarpine. Spontaneous seizures are observed in the long‐term period following the administration of convulsant doses of pilocarpine.Developmental studies show age‐dependent differences in the response of rats to pilocarpine. Seizures are first noted in 7–12 day‐old rats, and the adult pattern of behavioral and electroencephalographic sequelae of pilocarpine is seen in 15–21‐day‐old rats. During the third week of life the rats show an increased susceptibility to the convulsant action of pilocarpine relative to older and younger animals. The developmental progress of the convulsive response to pilocarpine does not correlate with evolution of the brain damage. The adult pattern of the damage is seen after a delay of 1–2 weeks in comparison with the evolution of seizures and status epilepticus. The susceptibility to seizures induced by pilocarpine increases in rats aged over 4 months.The basal ganglia curtail the generation and spread of seizures induced by pilocarpine. The caudate putamen, the substantia nigra, and the entopeduncular nucleus govern the propagation of pilocarpine‐induced seizures.The antiepileptic drugs diazepam, clonazepam, phenobarbital, valproate, and trimethadione protect against pilocarpine‐induced convulsions, while diphenylhydantoin and carbamazepine are ineffective. Ethosuximide and acetazolamide increase the suspectibility to convulsant action of pilocarpine. Lithium, morphine, and aminophylline also increase the susceptibility of rats to pilocarpine seizures.The pilocarpine seizure model may be of value in designing new therapeutic approaches to epilepsy.
Phorbol‐12,13‐dibutyrate antagonizes while forskolin potentiates the presynaptic autoreceptor‐mediated inhibition of [3H]‐5‐hydroxytryptamine release in rat hypothalamic slices
Authors: Ramdine R. , Galzin A.‐M. , Langer S. Z. 
Published: January 2005

AbstractIn superfused rat hypothalamic slices prelabeled with [3H]‐5‐hydroxytryptamine ([3H]‐5‐HT), the 5‐HT autoreceptor agonists 5‐methoxytryptamine and RU 24969 inhibited in a concentration‐dependent manner the electrically evoked release of [3H]‐5‐HT. Exposure to phorbol‐12,13‐dibutyrate increased in a concentration‐dependent manner the stimulation‐evoked overflow of [3H]‐5‐HT and shifted to the right the 5‐methoxytryptamine inhibition curve. Exposure to forskolin, a potent activator of adenylate cyclase, increased the stimulation‐evoked [3H]‐5‐HT overflow and shifted to the left the 5‐methoxytryptamine or RU 24969 inhibitory curves on transmitter release. A similar interaction was observed in the presence of 1‐isobutyl,3‐methylxanthine (IBMX), a phosphodiesterase inhibitor, or 8‐bromo‐cyclic AMP and the serotonin autoreceptor agonist 5‐methoxytryptamine. In the presence of phorbol‐12,13‐dibutyrate or forskolin, the enhancing effect of the 5‐HT autoreceptor antagonist methiothepin on the stimulation‐evoked [3H]‐5‐HT overflow was significantly less pronounced than in the absence of these compounds. These results indicate that the presynaptic 5‐HT autoreceptors that modulate the release of [3H]‐5‐HT in rat hypothalamic slices may be coupled to the phosphoinositide cycle and protein kinase C‐dependent mechanisms. In addition, the increase in intracellular level of cyclic AMP by forskolin, IBMX, and 8‐bromo‐cyclic AMP potentiates the inhibitory effects of the autoreceptor agonist 5‐methoxytryptamine on [3H]‐5‐HT release, although the mechanism of the interaction remains to be elucidated.
Frequency and amplitude gradients of spontaneous release along the length of the frog neuromuscular junction
Authors: Robitaille R. , Tremblay J. P. 
Published: January 2005

AbstractExperiments were done at the neuromuscular junctions (NMJs) of the cutaneous pectoris muscle of the frog to test the validity of the “spatial decay method” which uses simultaneous recording with two intracellular electrodes, each located in the muscle fiber near a distal end of the terminal. The miniature endplate potential (MEPP) peak amplitude recorded by each electrode is used to calculate the position of the release site producing it as well as its initial amplitude in front of its release site. The validity of the method was tested with a third focal electrode located between the two intracellular electrodes, at about 60–100 μm from one of the intracellular electrodes. the probability of spontaneous transmitter release was not uniform along the NMJ either in low or in normal Ca2+ + concentration. The release sites located in the region close to the first point of contact between the axon and the muscle fibre, usually close to the center of the NMJ, were spontaneously more active than the distal release sites. The degree of the steepness of proximodistal release gradients varied among different junctions. The less active regions tended to produce smaller MEPPs than did the more active ones. In fact, a correlation was found between the logarithm of MEPP frequency in a given region and the mean corrected MEPP amplitude in that region. These results also show that MEPP frequency was modulated to a greater extent than MEPP amplitude along the frog nerve terminal. The proximodistal gradient in MEPP frequency may be related to corresponding gradients in density and length of release sites along the junction, whereas MEPP amplitude gradients may be related to gradients in the length of release sites and/or postjunctional folds.
D1 receptor activation enhances sciatic nerve stimulation‐induced inhibition of nigrostriatal dopamine neurons
Authors: Kelland Mark D. , Freeman Arthur S. , Chiodo Louis A. 
Published: January 2005

AbstractNigrostriatal dopamine (NSDA) neurons have been hypothesized to play an important regulatory role in neostriatal sensorimotor integration. In order to provide further information on the nature of sensory modulation of NSDA cells, we have examined the pharmacology of the responsiveness of these neurons to peripheral nerve stimulation. The selective D1 dopamine receptor agonist SKF 38393 enhanced the normal inhibition of NSDA neurons produced by electrical stimulation of the sciatic nerve. The SKF 38393‐induced enhancement, but not the basal stimulation‐induced inhibition itself, was blocked by prior hemitransection of the forebrain and was reversed by the selective D1 antagonist SCH 23390 but not by the selective D2 antagonist 1‐sulpiride. SCH 23390 alone, however, exerted no effect on this inhibition. The selective D1 receptor agonist fenoldopam, which does not cross the blood‐brain barrier, also failed to alter the response to sciatic nerve stimulation (i.v. administration). Thus, central D1 receptors (rostral to the midbrain) appear to be involved in a system which mediates phasic control over sensory modulation of NSDA neuronal activity.
Dopamine transporter: Solubilization from dog caudate nucleus
Authors: Lew Robert , Grigoriadis Dimitri E. , Sharkey John , Kuhar Michael J. 
Published: January 2005

Abstract3H‐GBR 12935 was used to label the digitonin‐solubilized dopamine transporter from dog caudate nucleus. Specific binding to soluble fractions was observed in dog caudate but was absent in rat cerebellum. Binding to the solubilized transporter sites was saturable and of high affinity (Bmax = 2.57 ± 0.60 pmol/mg protein, KD = 23.42 ± 2.24 nM, n = 4). Heating or addition of trypsin abolished specific binding in the soluble fractions. In competition studies, soluble 3H‐GBR 12935 binding was inhibited by mazindol, GBR 12909, nomifensine, dimethocaine, dopamine, (−) cocaine, and (+) cocaine in a manner typical of binding to the dopamine transporter. As expected, tomoxetine and citalopram, inhibitors of norepinephrine and serotonin uptake, respectively, were weak competitors of 3H‐GBR 12935 binding.
Cholinergic modulation of frequency receptive fields in auditory cortex: I. Frequency‐specific effects of muscarinic agonists
Authors: McKenna Thomas M. , Ashe John H. , Weinberger Norman M. 
Published: January 2005

AbstractPreviously we reported that acetylcholine (ACh) and acetyl‐beta‐methacholine (MCh) modify responses of neurons in auditory cortex to individual frequencies. The purpose of this study was to determine whether muscarinic agonists produce frequency‐specific alterations or general changes in cellular responses. Frequency‐specific modifications would be evident in alterations of frequency receptive fields (FRF) that differed across frequencies while general effects would be seen as changes that were more or less the same over frequencies. Responses of single neurons to designated sets of tones were recorded in the auditory cortex of chronically prepared awake cats before, during, and following ejection of ACh or MCh by iontophoresis or micropressure using multibarrel micropipettes. Frequency receptive fields were determined by presenting isointensity tones across a range of frequencies including the cell's best frequency (BF) to tone onset. FRF for “off” and “sustained (through)” responses were also determined quantitatively. The effects of ACh and MCh were predominantly frequency‐specific (77%, 39/51 cells); general changes (19%, 10/51) and no effects (4%, 2/51) were less likely. Frequency‐specific effects involved both facilitation and reduction of the same response component to different frequencies within the same neuron. For responses to tone onset (but not “through” and “off” responses), agonists were more likely to produce a decrease at the BF while simultaneously increasing responses to other frequencies. Agonists could increase or decrease frequency selectivity. Effects of agonists could be blocked by atropine, suggesting involvement of muscarinic receptors.
Quantitative autoradiographic distribution of [3H]AF‐DX 116 muscarinic‐M2 receptor binding sites in rat brain
Authors: Regenold William , Araujo Dalia M. , Quirion Remi 
Published: January 2005

AbstractThe distribution of muscarinic‐M2 receptors in rat brain was investigated by in vitro autoradiography using [3H]AF‐DX 116, a putative probe for the muscarinic‐M2 receptor subtype. Incubation of rat brain coronal sections with 10 nM [3H]AF‐DX 116 showed highest binding site densities in discrete areas such as the superior colliculus and certain thalamic and brainstem nuclei, similar to the distribution reported for [2H]acetylcholine/M2 sites. [3H]AF‐DX 116 site densities were markedly lower in forebrain areas such as cortex, striatum, and hippocampus, in contrast to the distribution seen for [3H]pirenzepine‐M1 binding sites, which were concentrated in these forebrain areas; however, differential patterns of labeling were observed for the two muscarinic‐M2 probes, [3H]AF‐DX 116 and [3H]acetylcholine, in the hippocampal formation. Although [3H]AF‐DX 116 binding was broadly distributed in multiple subfields of the hippocampus, [3H]acetylcholine binding was discretely distributed in a manner resembling that of acetylcholinesterase staining. This suggests the existence of muscarinic‐M2 subtypes in the CNS, especially in the hippocampal formation.
Substantia nigra 6‐hydroxydopamine lesions alter dopaminergic synaptic markers in the nucleus basalis magnocellularis and striatum of rats
Authors: Geula Changiz , Slevin John T. 
Published: January 2005

AbstractRecent findings have demonstrated the existence of dopaminergic (DA) markers in the nbM of the human brain and a reduction of these markers in both the nbM and the striatum of patients suffering from Alzheimer's disease (AD). To investigate the source of the DA synaptic markers found in the nbM, rats received unilateral 6‐OHDA lesions of the substantia nigra pars compacta (SNc). The SNc lesions caused signigificant reductions in DA and DOPAC but not HVA in the nbM and the striaum; 3H‐sulpiride binding to D2 receptors ipsilateral to the SNc lesion was significantly increased in the stratum (16%), consistent with denervation supersensitivity, but single‐point analysis showed no significant changes in the nbM. These data suggest that the decreases in DA and 3H‐spiperone binding levels observed in the nbM of AD patients may be due to partial destruction of DA nbM afferent projections from the brainstem.