bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of the release of 5‐hydroxytryptamine in the median raphe nucleus of the rat by catecholaminergic afferents
Authors: Adell Albert , Artigas Francesc 
Published: March 2003

AbstractThe present study was conducted in order to examine the influence of catecholaminergic afferents on the release of serotonin in the median raphe nucleus in vivo. To this aim, selective dopamine D1 and D2, and α1‐ and α2‐adrenergic agonists and antagonists were administered locally (1, 10 and 100 μm) through a dialysis probe implanted in the median raphe nucleus of freely moving rats. The D1 and D2 agonists, (±)‐1‐phenyl‐2,3,4,5‐tetrahydro‐(1H)‐3‐benzazepine‐7,8‐diol (SKF‐38393) and quinpirole, respectively, and the D1 and D2 antagonists,
r‐(+)‐7‐chloro‐8‐hydroxy‐3‐methyl‐1‐phenyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine (SCH‐23390) and raclopride, respectively, did not alter the release of serotonin in the median raphe nucleus. The α1‐adrenoceptor agonist phenylephrine did not modify the release of serotonin in this nucleus, although an increased release was observed when the more potent α1‐adrenoceptor agonist cirazoline was used. In contrast, the α1‐adrenoceptor antagonist prazosin reduced the release of 5‐hydroxytryptamine (5‐HT) in a concentration‐dependent manner. The release of 5‐HT was also reduced by the α2‐adrenoceptor agonist clonidine and increased by the α2‐adrenoceptor antagonist 2‐methoxy‐idazoxan (RX821002). These results indicate that the release of serotonin in the median raphe nucleus does not appear to be regulated by dopaminergic afferents through the activation of dopamine D1 or D2 receptors. On the contrary, it is suggested that endogenous noradrenaline exerts a direct tonic stimulatory control on the release of serotonin through α1‐adrenoceptors, and an indirect tonic inhibitory influence through α2‐adrenoceptors located probably in noradrenergic nerve terminals within the median raphe nucleus.
Hu‐Bcl‐2 transgenic mice with supernumerary neurons exhibit timing impairment in a complex motor task
Authors: Rondi‐Reig Laure , Lohof Ann , Dubreuil Yolande Lemaigre , Delhaye‐Bouchaud Nicole , Martinou Jean‐Claude , Caston Jean , Mariani Jean 
Published: March 2003

AbstractProgrammed neuronal cell death is common during development, and is thought to be important in the elimination of errors in axonal projection, cell position and sculpting of neuronal circuits. However, the potential importance of programmed cell death for complex behaviour in the adult animal has never been addressed. We studied motor abilities in a strain of transgenic mice with neuronal overexpression of the human Bcl‐2 protein, which have supernumerary neurons due to reduced developmental cell death. Our results show that these mice have a clear deficiency in fine timing of motor coordination without impairment of basic motor functions. This is the first indication that altered developmental cell death and the consequent neuronal surplus can impair complex behaviour in the adult animal.
Acute application of NGF increases the firing rate of aged rat basal forebrain neurons
Authors: Albeck D. S. , Bäckman C. , Veng L. , Friden P. , Rose G. M. , Granholm A. ‐C. E. 
Published: March 2003

AbstractNerve growth factor (NGF) has been widely used in animal models to ameliorate age‐related neurodegeneration, but it cannot cross the blood–brain barrier (BBB). NGF conjugated to an antibody against the transferrin receptor (OX‐26) crosses the BBB and affects the biochemistry and morphology of NGF‐deprived basal forebrain neurons. The rapid actions of NGF, including electrophysiological effects on these neurons, are not well understood. In the present study, two model systems in which basal forebrain neurons either respond dysfunctionally to NGF (aged rats) or do not have access to target‐derived NGF (intraocular transplants of forebrain neurons) were tested. One group of transplanted and one group of aged animals received unconjugated OX‐26 and NGF comixture as a control, while other groups received replacement NGF in the form of OX‐26–NGF conjugate during the 3 months preceding the electrophysiological recording session. Neurons from animals in both the transplanted and aged control groups showed a significant increase in firing rate in response to acute NGF application, while none of the conjugate‐treated groups or young intact rats showed any response. After the recordings, forebrain transplants and aged brains were immunocytochemically stained for the low‐affinity NGF receptor. All conjugate treatment groups showed significantly greater staining intensity compared to controls. These data from both transplants and aged rats in situ indicate that NGF‐deprived basal forebrain neurons respond to acute NGF with an increased firing rate. This novel finding may have importance even for long‐term biological effects of this trophic factor in the basal forebrain.
Neuroendocrine responses to an emotional stressor: evidence for involvement of the medial but not the central amygdala
Authors: Dayas C. V. , Buller K. M. , Day T. A. 
Published: March 2003

AbstractThe amygdala plays a pivotal role in the generation of appropriate responses to emotional stimuli. In the case of emotional stressors, these responses include activation of the hypothalamic–pituitary–adrenal (HPA) axis. This effect is generally held to depend upon the central nucleus of the amygdala, but recent evidence suggests a role for the medial nucleus. In the present study, c‐fos expression, amygdala lesion and retrograde tracing experiments were performed on adult rats in order to re‐evaluate the role of the central as opposed to the medial amygdala in generating neuroendocrine responses to an emotional stressor. Brief restraint (15 min) was used as a representative emotional stressor and was found to elicit c‐fos expression much more strongly in the medial than central nucleus of the amygdala; relatively few Fos‐positive cells were seen in other amygdala nuclei. Subsequent experiments showed that ibotenic acid lesions of the medial amygdala, but not the central amygdala, greatly reduced restraint‐induced activation of cells of the medial paraventricular nucleus, the site of the tuberoinfundibular corticotropin‐releasing factor cells that constitute the apex of the HPA axis. Medial amygdala lesions also reduced the activation of supraoptic and paraventricular nucleus oxytocinergic neurosecretory cells that commonly accompanies stress‐induced HPA axis activation in rodents. To assess whether the role of the medial amygdala in the control of neuroendocrine cell responses to emotional stress might involve a direct projection to such cells, retrograde tracing of amygdala projections to the paraventricular nucleus was performed in combination with Fos immunolabelling. This showed that although some medial amygdala cells activated by exposure to an emotional stressor project directly to the paraventricular nucleus, the number is very small. These findings provide the first direct evidence that it is the medial rather than the central amygdala that is critical to hypothalamic neuroendocrine cell responses during an emotional response, and also provide the first evidence that the amygdala governs oxytocin as well as HPA axis responses to an emotional stressor.
Regionalization of Fos immunostaining in rat accessory olfactory bulb when the vomeronasal organ was exposed to urine
Authors: Inamura Kouhei , Kashiwayanagi Makoto , Kurihara Kenzo 
Published: March 2003

AbstractThe distribution of Fos‐immunoreactive (Fos‐ir) cells in the accessory olfactory bulb (AOB) of rats following vomeronasal organ exposure to urine was studied. Following exposure to male and female Wistar rat urine, Fos‐ir cells were found in the mitral/tufted cell layer, granule cell layer and periglomerular cell layer of the AOB of female Wistar rat, with the highest number in the granule cell layer. Exposure to water or removal of the vomeronasal organ suppressed the expression of Fos‐ir cells. These results suggest that female Wistar rats specifically detect urinary substances derived from male or female Wistar rats via the vomeronasal organ. Exposure of the vomeronasal organ of female Wistar rats to male Wistar urine induced the appearance of many more Fos‐ir cells in all layers of the AOB than exposure to female Wistar urine. As for the mitral/tufted cell layer, the density of Fos‐ir cells in the rostral portion (Gi2α‐positive) of all regions of the AOB was about twice as high as that in the caudal portion when male urine was given. The distribution pattern of Fos‐ir cells in response to female urine was not identical to that in response to male urine. That is, the density of Fos‐ir cells in the caudal portion was slightly larger than that in the rostral portion in the lateral region, while in other regions the density in the rostral portion was higher than that in the caudal portion. It is likely that information from different pheromones is transmitted to the higher brain regions through the different regions of the AOB.
Horizontal cells of the rabbit retina are non‐selectively connected to the cones
Authors: Hack Iris , Peichl Leo 
Published: March 2003

AbstractMammalian horizontal cells have generally been assumed to be spectrally non‐selective in their cone contacts until recently, when specific contacts have been found for some species. The rabbit retina is frequently studied as a representative of dichromatic mammalian retinae. These are the reasons for elucidating the connections of the two types of horizontal cells (A‐HCs and B‐HCs) with the green‐sensitive and blue‐sensitive cones of the rabbit retina. Individual A‐HCs and B‐HCs were revealed by Lucifer Yellow injections, the total cone population overlying them was stained using peanut agglutinin, and the blue cones among these were identified by the antiserum JH 455 against blue cone opsin. Both A‐HCs and B‐HCs indiscriminately contact the two cone types available. This holds for the green cone‐dominated dorsal retina and the blue cone‐dominated ventral retina. No evidence was found for a third, potentially blue cone‐selective, horizontal cell type [postulated by Famiglietti, E. V. (1990) Brain Res., 535, 174–179].
Stretch‐activated cation channels of leech neurons: characterization and role in neurite outgrowth
Authors: Calabrese B. , Manzi S. , Pellegrini M. , Pellegrino M. 
Published: March 2003

AbstractThe goal of this study was to characterize the stretch‐activated ion channels (SACs) of adult identified neurons of the leech Hirudo medicinalis and to test the role of SACs in neurite outgrowth of isolated cells. Using cell‐attached patch recording, we established that SACs are densely distributed in the growth cone membrane of cultured neurons. In excised patches, we found that these channels are permeable to Ca2+, as well as to monovalent cations. The channels are blocked by the extracellular application of gadolinium (Gd3+), amiloride and gentamicin. Amiloride and gentamicin, respectively, induce a partial and complete voltage‐dependent block. Time‐lapse video recordings of neurite outgrowth from single cultured neurons were used to study the effects of blocking SACs with gentamicin. Within 20 h of plating in the presence of the aminoglycoside, the total length of neuronal arborization was significantly greater than that measured in its absence. The amount of assembled axon per unitary surface area remained constant over 40 h and did not differ significantly with or without gentamicin. Our findings show that SACs of leech neurons admit Ca2+, are densely distributed in the growth cone membrane and exhibit typical pharmacological features of mechanotransducer ion channels. In addition, our data suggest that these cation channels participate in the early interaction between growing neurites and culture substrate.
Optic flow illusion and single neuron behaviour reconciled by a population model
Authors: Lappe Markus , Duffy Charles J. 
Published: March 2003

AbstractRadial patterns of optic flow contain a centre of expansion that indicates the observer’s direction of self‐movement. When the radial pattern is viewed with transparently overlapping unidirectional motion, the centre of expansion appears to shift in the direction of the unidirectional motion [Duffy, C.J. & Wurtz, R.H. (1993) Vision Res., 33, 1481–1490]. Neurons in the medial superior temporal (MST) area of monkey cerebral cortex are thought to mediate optic flow analysis, but they do not shift their responses to parallel the illusion created by transparent overlap. The population‐based model of optic flow analysis proposed by Lappe and Rauschecker replicates the illusory shift observed in perceptual studies [Lappe, M. & Rauschecker, J.P. (1995) Vision Res., 35, 1619–1631]. We analysed the behaviour of constituent neurons in the model, to gain insight into neuronal mechanisms underlying the illusion. Single model neurons did not show the illusory shift but rather graded variations of their response specificity. The shift required the aggregate response of the population. We compared the model’s predictions about the behaviour of single neurons with the responses recorded from area MST. The predicted distribution of overlap effects agreed with that observed in area MST. The success of the population‐based model in predicting the illusion and the neuronal behaviour suggests that area MST uses the graded responses of single neurons to create a population response that supports optic flow perception.
Release of endogenous dopamine in cultured mesencephalic neurons: influence of dopaminergic agonists and glucocorticoid antagonists
Authors: Rougé‐Pont Françoise , Abrous Djoher Nora , Le Moal Michel , Piazza Pier Vincenzo 
Published: March 2003

AbstractSeveral electrochemical techniques allow the measurement of dopamine release in freely moving animals and brain slices. In this report, we applied one of these techniques, coulometry, coupled to high‐performance liquid chromatography (HPLC), to the study of dopamine release in primary cultures of embryonic mesencephalic dopaminergic neurons. Between day 9 and 33 of culture, concentrations of dopamine, above the detection threshold, were found in the incubation buffer (Krebs ringer buffer, KRB). Concentrations of dopamine in the incubation buffer reflected neuronal release as they were: (i) positively correlated with the number of tyrosine hydroxylase‐positive dopamine neurons in the culture; (ii) tetrodotoxin (TTX) sensitive and Ca2+ dependent; (iii) increased by a depolarizing stimulus, e.g. K+ (20 m
m), or by the indirect dopamine agonists amphetamine and cocaine; (iv) decreased by a hyperpolarizing stimulus, e.g. the dopamine D2‐like receptor agonist quinpirole. Dopamine release in this model was also sensitive to the manipulation of glucocorticoids, potent modulators of dopamine release in vivo. Long‐term treatment of the cell cultures with RU 39305, a selective antagonist of glucocorticoid receptors (GR), but not with spironolactone, a selective antagonist of mineralocorticoid receptors (MR), dose‐dependently decreased K+‐stimulated dopamine release. In conclusion, these results demonstrate an in vitro model that allows the studying of the release of endogenous dopamine in cell cultures and the effects of glucocorticoid hormones on the release dynamics.
Native human neocortex release‐regulating dopamine D2 type autoreceptors are dopamine D2 subtype
Authors: Fedele Ernesto , Fontana Giovanni , Munari Claudio , Cossu Massimo , Raiteri Maurizio 
Published: March 2003

AbstractDopamine (DA) autoreceptors expressed at DA nerve terminals regulate DA release. Considerable evidence has indicated that, in rodents, these autoreceptors belong to the D2 type of the DA receptor family, which, in turn, comprises the D2, D3 and D4 subtypes. We investigated here, for the first time, the subclassification of native human DA autoreceptors by studying the release of [3H]DA evoked by electrical stimulation in fresh human neocortical slices. The results have been compared with those obtained in three animal systems: rat neocortical and striatal slices and rat mesencephalic neuronal cultures. In human neocortical slices, the D2/D3 receptor agonist quinpirole (1 n
m–10 μm) inhibited tritium release with a calculated EC50 of 17 n
m and a maximal inhibition of ≈ 75% reached at 1 μm. In the presence of the D2/D3 receptor antagonist (–)‐sulpiride (0.1 and 1 μm), the concentration–response curve of quinpirole was shifted to the right, and the apparent pA2 mean value was 8.5 (8.14–8.77); on the other hand, the inhibitory effects of quinpirole were not affected by the D3 receptor‐selective antagonist [7‐N,N‐dipropylamino‐5,6,7,8‐tetrahydro‐naphtho(2,3b) dihydro,2,3‐furane] (S 14297) and the D4 receptor‐selective antagonist 3‐(4‐[4‐chlorophenyl]piperazin‐1‐yl)‐methyl‐1H‐pyrrolo [2,3‐b]pyridine (L‐745,870) (0.01–1 μm in each case). Superimposable results have been obtained when the release was elicited from rat striatal slices or dopamine mesencephalic neurons in culture, whereas quantitative differences emerged in the case of rat cortical slices. It is concluded that in human brain, as well as in rat brain, the release of DA in the terminal region of midbrain dopaminergic neurons is regulated through autoreceptors of the D2 subtype.
Reduced hippocampal LTP in mice lacking a presynaptic protein: complexin II
Authors: Takahashi Sei‐ichi , Ujihara Hisamitsu , Huang Guang‐Zhe , Yagyu Ken‐ichi , Sanbo Makoto , Kaba Hideto , Yagi Takeshi 
Published: March 2003

AbstractThe SNAP receptor (SNARE) complex is a core complex specialized for synaptic vesicle exocytosis, and the binding of SNAPs to the complex is an essential step for neurotransmitter release. Complexin I and II have been identified as SNARE‐complex‐associated proteins. Importantly, complexins compete with α‐SNAP for binding to the complex, suggesting that complexins may modulate neurotransmitter release process. To examine this possibility and to understand the physiological function of complexins, we generated complexin II knockout mice. The complexin‐II‐deficient mice (–/–) were viable and fertile, and appeared normal. Electrophysiological recordings in the mutant hippocampus showed that ordinary synaptic transmission and paired‐pulse facilitation, a form of short‐term synaptic plasticity, were normal. However, long‐term potentiation (LTP) in both CA1 and CA3 regions was impaired, suggesting that complexin II may not be essential for synaptic vesicle exocytosis, but it does have a role in the establishment of hippocampal LTP.
Calpain activation and inhibition in organotypic rat hippocampal slice cultures deprived of oxygen and glucose
Authors: Brana C. , Benham C. D. , Sundstrom L. E. 
Published: March 2003

AbstractIt has been suggested that, after ischaemia, activation of proteases such as calpains could be involved in cytoskeletal degradation leading to neuronal cell death. In vivo, calpain inhibitors at high doses have been shown to reduce ischaemic damage and traumatic brain injury, however, the relationship between calpain activation and cell death remains unclear. We have investigated the role of calpain activation in a model of ischaemia based on organotypic hippocampal slice cultures using the appearance of spectrin breakdown products (BDPs) as a measure of calpain I activation. Calpain I activity was detected on Western blot immediately after a 1‐h exposure to ischaemia. Up to 4 h post ischaemia, BDPs were found mainly in the CA1 region and appeared before uptake of the vital dye propidium iodide (PI). 24 h after the insult, BDPs were detected extensively in CA1 and CA3 pyramidal cells, all of which was PI‐positive. However, there were many more PI‐positive cells that did not have BDPs, indicating that the appearance of BDPs does not necessarily accompany ischaemic cell death. Inhibition of BDP formation by the broad‐spectrum protease inhibitor leupeptin was not accompanied by any neuroprotective effects. The more specific and more cell‐permeant calpain inhibitor MDL 28170 had a clear neuroprotective effect when added after the ischaemic insult. In contrast, when MDL 28170 was present throughout the entire pre‐ and post‐incubation phases, PI labelling actually increased, indicating a toxic effect. These results suggest that calpain activation is not always associated with cell death and that, while inhibition of calpains can be neuroprotective under some conditions, it may not always lead to beneficial outcomes in ischaemia.
Inhibition of glial scarring in the injured rat brain by a recombinant human monoclonal antibody to transforming growth factor‐β2
Authors: Logan Ann , Green Jonathan , Hunter Allison , Jackson Ronald , Berry Martin 
Published: March 2003

AbstractThe transforming growth factor‐βs (TGF‐βs) are potent fibrogenic factors implicated in numerous central nervous system (CNS) pathologies in which fibrosis and neural dysfunction are causally associated. In this study, we aim to limit the fibrogenic process in a model of CNS scarring using a recombinant human monoclonal antibody, derived from phage display libraries and specific to the active form of the TGF‐β2 isoform. The implicit inference of the work was that, as such antibodies are potential pharmacological agents for the treatment of human CNS fibrotic diseases, validation of efficacy in a mammalian animal model is a first step towards this end. Treatment of cerebral wounds with the anti‐TGF‐β2 antibody led to a marked attenuation of all aspects of CNS scarring, including matrix deposition, formation of an accessory glial‐limiting membrane, inflammation and angiogenesis. For example, in the wound, levels of: (i) the connective tissue components fibronectin, laminin and chondroitin sulphate proteoglycan; and (ii) wound‐responsive cells including astrocytes and macrophages/microglia, were markedly reduced. Our findings suggest that such synthetic anti‐fibrotic TGF‐β antibodies are potentially applicable to a number of human CNS fibrotic diseases to arrest the deposition of excessive extracellular matrix components, and maintain and/or restore functional integrity.
Postnatal development of GABAB receptor‐mediated modulation of voltage‐activated Ca2+ currents in mouse brain‐stem neurons
Authors: Zhang W. , Elsen F. , Barnbrock A. , Richter D. W. 
Published: March 2003

AbstractGABAB receptors modulate respiratory rhythm generation in adult mammals. However, little is currently known of their functional significance during postnatal development. In the present investigation, the effects of GABAB receptor activation on voltage‐activated Ca2+ currents were examined in rhythmically active neurons of the pre‐Bötzinger complex (PBC). Both low‐ (LVA) and high‐voltage‐activated (HVA) Ca2+ currents were present from the first postnatal day (P1). The density of LVA Ca2+ currents increased during the first week, whilst the density of HVA Ca2+ currents increased after the first week. In the second postnatal week, the HVA Ca2+ currents were composed of L‐ (47 ± 10%) and N‐type (21 ± 8%) currents plus a ‘residual’ current, whilst there were no N‐type currents detectable in the first few days. The GABAB receptor agonist baclofen (30 μm) increased LVA Ca2+ currents (30 ± 11%) at P1–P3, but it decreased the currents (35 ± 11%) at P7–P15 without changing its time course. At all ages, baclofen (30 μm) decreased the HVA Ca2+ currents by ≈ 54%. Threshold of baclofen effects on both LVA and HVA Ca2+ currents was 5 μm at P1–P3 and lower than 1 μm at P7–P15. The effect of baclofen was abolished in the presence of the GABAB receptor antagonist CGP 55845A (50 n
m). We conclude that both LVA and HVA Ca2+ currents increased postnatally. The GABAB receptor‐mediated modulation of these currents undergo marked developmental changes during the first two postnatal weeks, which may contribute essentially to modulation of respiratory rhythm generation.