bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation by adenosine of both muscarinic M1‐facilitation and M2‐inhibition of [3H]‐acetylcholine release from the rat motor nerve terminals
Authors: Oliveira Laura , Timóteo M. Alexandrina , Correia‐de‐Sá Paulo 
Published: March 2003

AbstractThe crosstalk between adenosine and muscarinic autoreceptors regulating evoked [3H]‐acetylcholine ([3H]‐ACh) release was investigated on rat phrenic nerve‐hemidiaphragm preparations. Motor nerve terminals possess facilitatory M1 and inhibitory M2 autoreceptors that can be activated by McN‐A‐343 (1–30 µm) and oxotremorine (0.3–100 µm), respectively. The muscarinic receptor antagonist, dicyclomine (3 nm−10 µm), caused a biphasic (inhibitory/facilitatory) effect, indicating that M1‐facilitation prevails during 5 Hz stimulation trains. Concomitant activation of AF–DX 116‐sensitive M2 receptors was partially attenuated, as pretreatment with M1 antagonists, muscarinic toxin 7 (MT‐7, 0.1 nm) and pirenzepine (1 nm), significantly enhanced inhibition by oxotremorine. Activation of A2A‐adenosine receptors with CGS 21680C (2 nm) (i) potentiated oxotremorine inhibition, and (ii) shifted McN‐A‐343‐induced facilitation into a small inhibitory effect. Conversely, the A1‐receptor agonist, R‐N6‐phenylisopropyl adenosine (R‐PIA, 100 nm), attenuated the inhibitory effect of oxotremorine, without changing facilitation by McN‐A‐343. Synergism between A2A and M2 receptors is regulated by a reciprocal interaction with facilitatory M1 receptors, which may be prevented by pirenzepine (1 nm). During 50 Hz‐bursts, facilitation (M1) of [3H]‐ACh release by McN‐A‐343 disappeared, while the inhibitory (M2) effect of oxotremorine became predominant. This muscarinic shift results from the interplay with A2A receptors, as it was precluded by the selective A2A receptor antagonist, ZM 241385 (10 nm). In conclusion, when the muscarinic M1 positive feedback loop is fully operative, negative regulation of ACh release is mediated by adenosine A1 receptors. During high frequency bursts, tonic activation of A2A receptors promotes M2 autoinhibition by braking the M1 receptor operated counteraction.
Posterior parietal cortex control of reach‐to‐grasp movements in humans
Authors: Chapman Heidi , Gavrilescu Maria , Wang Hong , Kean Michael , Egan Gary , Castiello Umberto 
Published: March 2003

AbstractThe aim of the present study was to ascertain the neural correlates for the integration of visual information with the control of the reach‐to‐grasp action in the healthy human brain. Nine adult subjects (18–38 years; four females and five males) were scanned using functional magnetic resonance imaging while reaching‐to‐grasp a three‐dimensional target. Results demonstrated differential activation of the parietal cortices according to the number of potential targets to be taken into account before movement initiation and the variability of target location. Comparing conditions where a target object that can appear at an unpredictable location with conditions where the target object appears at a predictable location revealed activations in the left superior parietal lobule, the left parieto‐occipital sulcus and the right intraparietal sulcus. Results are discussed in terms of visual selective attention and action planning.
Variations in cell density in the ganglion cell layer of the retina as a function of ocular pigmentation
Authors: Donatien Philippe , Aigner Bernhard , Jeffery Glen 
Published: March 2003

AbstractOcular melanin regulates retinal development, including cell density gradients in the central retina, a region essential for normal visual acuity. In albinos this region is underdeveloped and peak cell numbers are reduced. It is not known whether there is a dosage relationship between pigmentation and the degree of this underdevelopment, as studies of the retinal effects of albinism have commonly used rodents. These have poorly developed central regions even in the wild type. Rabbits, however, have a unique, highly specialized, visual streak in the central retina where cell density gradients are very steep and these are reduced in albinos. Here, cell densities in the ganglion cell layer of separate groups of rabbits, with different levels of ocular pigmentation and known mutations of the tyrosinase gene coding sequence, were examined. These revealed reductions in peak cell densities and/or in the regions over which high cell densities were maintained in all hypopigmented phenotypes. There was no dosage relationship between levels of pigmentation and deficits in the ganglion cell layer as animals with relatively small reductions in retinal pigment had deficits comparable to those found in albinos. The greatest variability between pigmentation phenotypes was between the two completely unpigmented strains. Consequently, although pigment may regulate the development of the central retina, this study failed to show that it does so in a dose‐dependent manner.
Reminder effects – reconsolidation or retrieval deficit? Pharmacological dissection with protein synthesis inhibitors following reminder for a passive‐avoidance task in young chicks
Authors: Anokhin Konstantin V. , Tiunova Anna A. , Rose Steven P. R. 
Published: March 2003

AbstractIt is generally accepted that memory formation involves an irreversible passage via labile phases to the stable form of ‘long‐term memory’ impervious to amnestic agents such as protein synthesis inhibitors. However, recent experiments demonstrate that reactivation of memory by way of a reminder renders it labile to such inhibitors, suggesting that such retrieval is followed by a so‐called reconsolidation process similar or identical in its cellular and molecular correlates to that occurring during the initial consolidation. We compared the effects of the protein synthesis inhibitor anisomycin and the glycoprotein synthesis inhibitor 2‐deoxygalactose on the temporal dynamics and pharmacological sensitivity of initial consolidation and memory expression following a reminder in a one‐trial passive‐avoidance task in day‐old chicks. This comparison revealed three differences between the action of the inhibitors on newly formed compared with reactivated memory. First, the recall deficit after the reminder was temporary, whilst the amnesia following inhibitor treatment during training was stable. Second, the sensitive period for the effect of anisomycin was shorter in the reminder than in the training situation. Third, the effective dose for either inhibitor for reminder‐associated amnesia was several times lower than for amnesia developing after training. Thus though like initial consolidation, memory expression at delayed periods following reminder depends on protein and glycoprotein synthesis, the differences between the temporal and pharmacological dynamics in the two situations point to the distinct character of the molecular processes involved in postreminder effects.
The contribution of the intrinsic excitability of vestibular nucleus neurons to recovery from vestibular damage
Authors: Darlington Cynthia L. , Dutia Mayank B. , Smith Paul F. 
Published: March 2003

AbstractDamage to the peripheral vestibular system results in a syndrome of ocular motor and postural abnormalities that partially and gradually abate over time in a process known as ‘vestibular compensation’. The first, rapid, phase of compensation has been associated with a recovery of spontaneous resting activity in the ipsilateral vestibular nucleus complex (VNC), as a consequence of neuronal and synaptic plasticity. Increasing evidence suggests that normal VNC neurons in labyrinthine‐intact animals, as well as ipsilateral VNC neurons following unilateral vestibular deafferentation (UVD), rely to some extent on intrinsic pacemaker activity provided by voltage‐dependent conductances for their resting activity. Modification of this intrinsic pacemaker activity may underlie the recovery of resting activity that occurs in ipsilateral VNC neurons following UVD. This review summarizes and critically evaluates the ‘intrinsic mechanism hypothesis’, identifying discrepancies amongst the current evidence and suggesting experiments that may test it further.
Specific expression of the cell cycle regulation proteins, GADD34 and PCNA, in the peri‐infarct zone after focal cerebral ischaemia in the rat
Authors: Imai H. , Harland J. , McCulloch J. , Graham D.I. , Brown S.M. , Macrae I.M. 
Published: March 2003

AbstractCell cycle proteins play key roles in cell survival or death under pathological conditions. Expression of growth arrest and DNA damage‐inducible protein, GADD34 and proliferating cell nuclear antigen (PCNA) have been investigated in the core and peri‐infarct zone at 2 and 24 h after middle cerebral artery occlusion (MCAO). At these times after MCAO, numerous GADD34‐positive cells were present, particularly in the peri‐infarct zone (e.g. 24 ± 4 and 52 ± 6 immunopositive cells/0.25 mm2 at 2 and 24 h, respectively, in cortex). PCNA‐immunopositive cells were barely detectable in the peri‐infarct zone at 2 h; however, numerous PCNA‐immunopositive cells were present in this zone by 24 h (0.7 ± 0.3 and 10.6 ± 1.5 immunopositive cells/0.25 mm2, respectively) as well as in the adjacent cortex and in the contralateral cingulate cortex. Most GADD34‐immunopositive cells coexpressed the neuronal marker Neu‐N with a smaller number coexpressing the microglial marker, Mrf‐1. Evidence of morphologically ‘abnormal’ and ‘normal’ GADD34 immunopositive neurons was found within the peri‐infarct zone. The majority of PCNA immunopositive cells were Mrf‐1 positive with a smaller number Neu‐N positive. Double‐labelling revealed colocalization of GADD34 and PCNA in some cells within the peri‐infarct zone and in the ependymal cells lining the ventricles. The presence of GADD34 and PCNA in a key anatomical location pertinent to the evolving ischaemic lesion indicates that GADD34, either alone or in combination with PCNA, has the potential to influence cell survival in ischaemically compromised tissue.
A point mutant of GAP‐43 induces enhanced short‐term and long‐term hippocampal plasticity
Authors: Hulo S. , Alberi S. , Laux T. , Muller D. , Caroni P. 
Published: March 2003

AbstractThe growth‐associated protein GAP‐43 (or neuromodulin or B‐50) plays a critical role during development in mechanisms of axonal growth and formation of synaptic networks. At later times, GAP‐43 has also been implicated in the regulation of synaptic transmission and properties of plasticity such as long‐term potentiation. In a molecular approach, we have analyzed transgenic mice overexpressing different mutated forms of GAP‐43 or deficient in GAP‐43 to investigate the role of the molecule in short‐term and long‐term plasticity. We report that overexpression of a mutated form of GAP‐43 that mimics constitutively phosphorylated GAP‐43 results in an enhancement of long‐term potentiation in CA1 hippocampal slices. This effect is specific, because LTP was affected neither in transgenic mice overexpressing mutated forms of non‐phosphorylatable GAP‐43 nor in GAP‐43 deficient mice. The increased LTP observed in transgenic mice expressing a constitutively phosphorylated GAP‐43 was associated with an increased paired‐pulse facilitation as well as an increased summation of responses during high frequency bursts. These results indicate that, while GAP‐43 is not necessary for LTP induction, its phosphorylation may regulate presynaptic properties, thereby affecting synaptic plasticity and the induction of LTP.
Involvement of Cajal–Retzius cells in robust and layer‐specific regeneration of the entorhino‐hippocampal pathways
Authors: Del Río José A. , Solé Marta , Borrell Víctor , Martínez Albert , Soriano Eduardo 
Published: March 2003

AbstractSevered adult CNS axons can extend over long distances when a permissive ‘milieu’, such as grafted Schwann cells or ensheathing cells, is provided. Moreover, functional blocking of endogenous inhibitory factors, such as Nogo‐A or proteoglycans, enhances the regeneration of axotomized neurons. Here we examine whether guidance cues available during the development of axonal pathways could also potentiate the regeneration of lesioned adult circuits. The Cajal–Retzius cells in the hippocampus are transient pioneer neurons that guide entorhino‐hippocampal afferents to their target layers. By using an in vitro model of axotomy of the entorhino‐hippocampal pathway we show that Cajal–Retzius cells triggered the regeneration of the axotomized entorhino‐hippocampal pathway. Furthermore, the regrowth induced by Cajal–Retzius cells was robust and its pattern was indistinguishable from that of the unlesioned entorhino‐hippocampal pathway. Thus, regenerating axons regrew in a layer‐specific fashion towards the appropriate target layers, making synaptic contacts with target pyramidal neurons. Interestingly, the ability of lesioned entorhinal axons to regrow was maintained for at least 9 days after axotomy. These results show that the growth‐promoting cells controlling the development of neural circuits will be a relevant approach to promoting the regeneration of lesioned adult CNS pathways.
The influence of selective lesions to components of the hippocampal system on the orientating response, habituation and latent inhibition
Authors: Oswald C. J. P. , Yee B. K. , Rawlins J. N. P. , Bannerman D. B. , Good M. , Honey R. C. 
Published: March 2003

AbstractThe contribution that components of the hippocampal system in the rat make to the modulation of attention or stimulus processing was assessed using several simple behavioural assays: the orienting response (OR) to a novel stimulus, the subsequent habituation and dishabituation of this OR, and the latent inhibition effect that typically results from repeated exposure to a stimulus. Excitotoxic lesions of components of the hippocampal system produce dissociable effects on the OR, habituation and latent inhibition: lesions of the entorhinal cortex have no effect on the OR or changes in the OR during exposure to a stimulus, but disrupt latent inhibition; lesions of the subiculum disrupt the OR but not latent inhibition; and lesions of the hippocampus disrupt the OR and latent inhibition. These effects have important implications for our understanding of habituation and latent inhibition, and the neural mechanisms involved in attentional modulation.
Multiple zonal projections of the nucleus reticularis tegmenti pontis to the cerebellar cortex of the rat
Authors: Serapide M. F. , Parenti R. , Pantò M. R. , Zappalà A. , Cicirata F. 
Published: March 2003

AbstractCompartmentalization (alternating labelled and unlabelled stripes) of mossy fibre terminals was found in the cerebellar cortex after iontophoretic injections of biotinylated dextran amine into discrete regions of the nucleus reticularis tegmenti pontis (NRTP). The zonal pattern was only observed when volumes of nuclear tissue ranging from 4.5 × 106 to 17.66 × 106 µm3 were impregnated. Up to nine compartments (i.e. up to five stripes separated by four interstripes) were found in crus I and in vermal lobule VI. Up to seven compartments (four stripes and three interstripes) were found in crus II; up to five compartments (three stripes and two interstripes) were identified in the lobulus simplex, the paraflocculus and vermal lobules IV, V and VII; up to three compartments (two stripes and one interstripe) were identified in the paramedian lobule and, finally, up to two compartments (one stripe and one interstripe) were identified in the copula pyramidis, in the flocculus and in vermal lobules II, III, VIII and IX. The projections of the NRTP are arranged according to a divergent/convergent projection pattern. From single injections in the NRTP, projections were traced to a set of cortical stripes widely distributed over the cerebellar cortex. The set of stripes labelled from different regions of the NRTP partially overlapped but complete overlap was never found. This finding revealed that the topographic combination of the projections of the NRTP to the cerebellar cortex is specific for each region of the NRTP. Finally, the projections to single cortical areas were arranged according to a pattern of compartmentalization that is specific for each cortical area, independent of the site of injection in the NRTP and of the number of stripes evident in the cortex.
Genomic responses of the brain to ischemic stroke, intracerebral haemorrhage, kainate seizures, hypoglycemia, and hypoxia
Authors: Tang Yang , Lu Aigang , Aronow Bruce J. , Wagner Kenneth R. , Sharp Frank R. 
Published: March 2003

AbstractRNA expression profiles in rat brain were examined 24 h after ischemic stroke, intracerebral haemorrhage, kainate‐induced seizures, insulin‐induced hypoglycemia, and hypoxia and compared to sham‐ or untouched controls. Rat oligonucleotide microarrays were used to compare expression of over 8000 transcripts from three subjects in each group (n = 27). Of the somewhat less than 4000 transcripts called ‘present’ in normal or treated cortex, 5–10% of these were up‐regulated 24 h after ischemia (415), haemorrhage (205), kainate (187), and hypoglycemia (302) with relatively few genes induced by 6 h of moderate (8% oxygen) hypoxia (15). Of the genes induced 24 h after ischemia, haemorrhage, and hypoglycemia, approximately half were unique for each condition suggesting unique components of the responses to each of the injuries. A significant component of the responses involved immune‐process related genes likely to represent responses to dying neurons, glia and vessels in ischemia; to blood elements in haemorrhage; and to the selectively vulnerable neurons that die after hypoglycemia. All of the genes induced by kainate were also induced either by ischemia, haemorrhage or hypoglycemia. This strongly supports the concept that excitotoxicity not only plays an important role in ischemia, but is an important mechanism of brain injury after intracerebral haemorrhage and hypoglycemia. In contrast, there was only a single gene that was down‐regulated by all of the injury conditions suggesting there is not a common gene down‐regulation response to injury.
Effect of systemic nitroglycerin on CGRP and 5‐HT afferents to rat caudal spinal trigeminal nucleus and its modulation by estrogen
Authors: Pardutz A. , Multon S. , Malgrange B. , Parducz A. , Vecsei L. , Schoenen J. 
Published: March 2003

AbstractSystemic administration of nitroglycerin, a nitric oxide donor, triggers in migraine patients a delayed attack of unknown mechanism. After puberty migraine is more prevalent in women. Attacks can be triggered by abrupt falls in plasma estrogen levels, which accounts in part for sexual dimorphism, but lacks an established neurobiological explanation. We studied the effect of nitroglycerin on the innervated area of calcitonin gene‐related peptide (CGRP) and serotonin‐immunoreactive afferents to the superficial laminae of the spinal portion of trigeminal nucleus caudalis, and its modulation by estrogen. In male rats, nitroglycerin produced after 4 h a significant decrease of the area innervated by CGRP‐immunoreactive afferents and an increase of that covered by serotonin‐immunoreactive fibres. These effects were not observed in the superficial laminae of thoracic dorsal horns. The effect of nitroglycerin was similar in ovariectomized females. In estradiol‐treated ovariectomized females the area in the spinal portion of trigeminal nucleus caudalis laminae I–II covered by CGRP‐immunoreactive fibres was lower and that of serotonin‐immunoreactive fibres was higher than in males and for both transmitters not significantly changed after nitroglycerin. The bouton size of CGRP profiles was smaller in estradiol‐treated ovariectomized females, whereas after nitroglycerin it decreased significantly but only in males and ovariectomized females. Nitroglycerin, i.e. nitric oxide, is thus able to differentially influence afferent fibres in the superficial laminae of rat spinal trigeminal nucleus caudalis. Estradiol modulates the basal expression of these transmitters and blocks the nitroglycerin effect. These data may contribute to understanding the mechanisms by which estrogens influence migraine severity and the triggering of attacks by nitric oxide.
Expression and distribution of metabotropic GABA receptor subtypes GABABR1 and GABABR2 during rat neocortical development
Authors: López‐Bendito G. , Shigemoto R. , Kulik A. , Paulsen O. , Fairén A. , Luján R. 
Published: March 2003

AbstractTo understand the possible contribution of metabotropic γ‐aminobutyric acid receptors (GABABR) in cortical development, we investigated the expression pattern and the cellular and subcellular localization of the GABABR1 and GABABR2 subtypes in the rat neocortex from embryonic day 14 (E14) to adulthood. At the light microscopic level, both GABABR1 and GABABR2 were detected as early as E14. During prenatal development, both subtypes were expressed highly in the cortical plate. Using double immunofluorescence, GABABR1 colocalized with GABABR2 in neurons of the marginal zone and subplate, indicating that these proteins are coexpressed and could be forming functional GABABRs during prenatal development in vivo. In contrast, only GABABR1 but not GABABR2 was detected in the tangentially migratory cells in the lower intermediate zone. During postnatal development, immunoreactivity for GABABR1 and GABABR2 was distributed mainly in pyramidal cells. Discrete GABABR1‐immunopositive cell bodies of interneurons were present throughout the neocortex. In addition, GABABR1 but not GABABR2 was found in identified Cajal‐Retzius cells in layer I. At the electron microscopic level, immunoreactivity for GABABR1 and GABABR2 was found in dendritic spines and dendritic shafts at extrasynaptic and perisynaptic sites throughout postnatal development. We further demonstrated the presynaptic localization of GABABR1 and GABABR2, as well as the association of the receptors with asymmetrical synaptic junctions. These results indicate potentially important roles for the GABABRs in the regulation of migratory processes during corticogenesis and in the modulation of synaptic transmission during early development of cortical circuitry.
Direct measurement of local raised subplasmalemmal calcium concentrations in growth cones advancing on an N‐cadherin substrate
Authors: Chadborn Neil , Eickholt Britta , Doherty Patrick , Bolsover Stephen 
Published: March 2003

AbstractWe have used the membrane‐localized calcium probe fura‐piperazine‐C12H25 (FFP‐18) to examine cytosolic calcium concentrations in a volume close to the plasmalemma. Although promotion of axon outgrowth by cell adhesion molecules requires extracellular calcium and is correlated with an opening of plasmalemmal channels, conventional indicators cannot detect a change in the calcium concentration in such stimulated growth cones. We have examined calcium signalling in chick retinal ganglion cell growth cones extending along stripes of N‐cadherin. Subplasmalemmal calcium concentrations, reported by FFP‐18, were significantly higher in these growth cones than in neighbouring growth cones on either fibronectin or polylysine. In contrast, the bulk cytosolic calcium concentration throughout the growth cone, as measured by Fura‐2, was identical in growth cones on and off the N‐cadherin stripes. Our results suggest that guidance cues can use extremely local calcium signals to control pathfinding decisions.