bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precise matching of olivo‐cortical divergence and cortico‐nuclear convergence between somatotopically corresponding areas in the medial C1 and medial C3 zones of the paravermal cerebellum
Authors: Apps R. , Garwicz M. 
Published: March 2003

AbstractThe paravermal cerebellar cortex contains three spatially separate zones (the C1, C3 and Y zones) which form a functionally coupled system involved in the control of voluntary limb movements. A series of ‘modules’ has been postulated, each defined by a set of olivary neurons with similar receptive fields, the cortical microzones innervated by these neurons and the group of deep cerebellar nuclear neurons upon which the microzones converge. A key feature of this modular organization is a correspondence between cortical input and output, irrespective of the zonal identity of the microzone. This was tested directly using a combined electrophysiological and bi‐directional tracer technique in barbiturate‐anaesthetized cats. During an initial operation, small injections of a mix of retrograde and anterograde tracer material (red beads combined with Fluoro‐Ruby or green beads combined with biotinylated dextran amine or Fluoro‐Emerald) were made into areas of the medial C1 and medial C3 zones in cerebellar lobule V characterized by olivo‐cerebellar input from the ventral forelimb. The inferior olive and the deep cerebellar nuclei were then scrutinized for retrogradely labelled cells and anterogradely labelled axon terminals, respectively. For individual experiments, the degree of C1–C3 zone terminal field overlap in the nucleus interpositus anterior was plotted as a function of either the regional overlap of single‐labelled cells or the proportion of double‐labelled cells in the dorsal accessory olive. The results were highly positively correlated, indicating that cortico‐nuclear convergence between parts of the two zones is in close proportion to the corresponding olivo‐cerebellar divergence, entirely consistent with the modular hypothesis.
Different spatiotemporal expression of DOC2 genes in the developing rat brain argues for an additional, nonsynaptic role of DOC2B in early development
Authors: Korteweg Niki , Denekamp Francien A. , Verhage Matthijs , Burbach J. Peter H. 
Published: March 2003

AbstractDOC2A and DOC2B are two homologous genes implicated in synaptic vesicle exocytosis. Their complementary, nonoverlapping expression patterns in adult rat brain suggest that they exert similar functions in different neurons. We have analysed the expression pattern of the two genes in the developing rat brain by in situ hybridization. Unexpectedly, we found no parallel expression of the two genes during development. DOC2B mRNA was highly expressed as early as embryonic day 12 (E12) throughout the neuroepithelium, long before synaptic transmission is functional, and the expression remained abundant from E12 onwards. In contrast, faint expression of DOC2A transcripts was first detected at E17 in ventral brain areas, and it extended gradually to other brain structures in the sequence of their ontology, i.e. structures that had formed first also expressed DOC2A first. At postnatal day 3, both genes were highly expressed throughout the brain. This overlapping expression diverged to the complementary distribution of the adult brain. The temporal and spatial differences in expression point to a functional divergence between these homologous genes during brain development: the pattern of DOC2A is consistent with its proposed synaptic function, whereas that of DOC2B suggests an additional, nonsynaptic role in proliferating cells.
Clonidine blocks stress‐induced reinstatement of heroin seeking in rats: an effect independent of locus coeruleus noradrenergic neurons
Authors: Shaham Yavin , Highfield David , Delfs Jill , Leung Shirley , Stewart Jane 
Published: March 2003

AbstractUsing a reinstatement procedure, it has been shown that intermittent footshock stress reliably reinstates extinguished drug‐taking behaviour in rats. Here we studied the role of noradrenaline (NE), one of the main brain neurotransmitters involved in responses to stress, in reinstatement of heroin seeking. We first determined the effect of clonidine, an alpha‐2 adrenergic receptor agonist that decreases NE cell firing and release, on stress‐induced reinstatement of heroin seeking. Rats were trained to self‐administer heroin (0.1 mg/kg per infusion, IV, three 3‐h sessions per day) for 9–10 days. Extinction sessions were given for up to 11 days during which saline was substituted for the drug. Tests for reinstatement were then conducted after exposure to intermittent footshock (5, 15 and 30 min, 0.5 mA). During testing, clonidine was injected systemically (10–40 μg/kg, i.p.) or directly into the lateral or fourth ventricles (1–3 μg). Clonidine (1–2 μg per site) or its charged analogue, 2‐[2,6‐diethylphenylamino]‐2‐imidazole (ST‐91, 0.5–1 μg per site), was also injected bilaterally into the locus coeruleus (LC), the main noradrenergic cell group in the brain. Clonidine blocked stress‐induced reinstatement of drug seeking when injected systemically or into the cerebral ventricles. In contrast, neither clonidine nor ST‐91 consistently altered stress‐induced reinstatement when injected into the locus coeruleus. We therefore studied the effect of lesions of the lateral tegmental NE neurons on stress‐induced reinstatement. 6‐Hydroxydopamine (6‐OHDA) lesions performed after training for heroin self‐administration had no effect on extinction of heroin‐taking behaviour, but significantly attenuated reinstatement induced by intermittent footshock. These data suggest that: (i) clonidine prevents stress‐induced relapse to heroin seeking by its action on neurons other than those of the locus coeruleus; and (ii) activation of the lateral tegmental NE neurons contributes to stress‐induced reinstatement of heroin seeking.
Age‐related impairment in LTP is accompanied by enhanced activity of stress‐activated protein kinases: analysis of underlying mechanisms
Authors: O'Donnell Eamonn , Vereker Emily , Lynch M. A. 
Published: March 2003

AbstractThe age‐related impairment in long‐term potentiation in the rat dentate gyrus is coupled with an increase in the proinflammatory cytokine, interleukin‐1β (IL‐1β). It is possible that this increase in IL‐1β might be a consequence of the age‐related increase in reactive oxygen species production in hippocampal tissue. In this study we set out to identify the underlying cause of the age‐related increase in reactive oxygen species production and to establish whether any consequences of such a change might impact on the ability of aged rats to sustain long‐term potentiation (LTP). We report that there was an age‐related increase in the activity of superoxide dismutase but no parallel increases in activities of glutathione peroxidase or catalase, while age‐related decreases in the concentration of the scavengers, vitamins E and C and glutathione were also observed. We propose that these compromises in antioxidative strategies may result in an increase in reactive oxygen species production. The data described indicate that IL‐1β and H2O2 increase the activity of two stress‐activated mitogen‐activated protein kinases, c‐Jun NH2‐terminal kinase (JNK) and p38 in vitro, while age‐related increases in both kinases were observed. We propose that the endogenous increase in these parameters which occurs with age induces the increase in activity of the stress‐activated kinases, which in turn impacts on the ability of the aged rat to sustain LTP.
Evolution of changes in neuronal activity in the subthalamic nucleus of rats with unilateral lesion of the substantia nigra assessed by metabolic and electrophysiological measurements
Authors: Vila M. , Périer C. , Féger J. , Yelnik J. , Faucheux B. , Ruberg M. , Raisman‐Vozari R. , Agid Y. , Hirsch E. C. 
Published: March 2003

AbstractCellular expression of cytochrome oxidase subunit I (COI) mRNA has recently been used as a metabolic marker for neuronal activity to study the functional changes in the subthalamic nucleus (STN) in parkinsonism. The previous experimental studies have been performed when the pathological state was stabilized at a maximal level. In order to determine the evolution of changes in neuronal activity in the STN after nigrostriatal denervation, we analysed by in situ hybridization the cellular expression of COI mRNA in the subthalamic neurons at different times, from 6 h to 14 days, after unilateral intranigral microinjection of 6‐hydroxydopamine (6‐OHDA) in rats. In parallel, the time‐dependent changes of the unit neuronal activity of subthalamic neurons have been recorded. Levels of COI mRNA increased by 41% in subthalamic neurons from 24 h after 6‐OHDA intoxication, to 14 days (+26%). Similarly, electrical activity started to increase slightly 24 h after lesion (+20%) and remained significantly higher at 14 days after the lesion (+189%). Changes in neuronal mean discharge rate were associated with changes in the pattern of spiking activity, from a regular firing pattern to an irregular one with a high bursting activity. These results show that: (i) the hyperactivity of the STN represents a very early phenomenon in the physiopathology of parkinsonian syndromes; and (ii) that changes in COI mRNA expression slightly precede changes in electrical neuronal activity.
Metabotropic glutamate receptors and blockade of glial Krebs cycle depress glycinergic synaptic currents of mouse hypoglossal motoneurons
Authors: Hülsmann Swen , Oku Yoshitaka , Zhang Weiqi , Richter Diethelm W. 
Published: March 2003

AbstractMetabotropic glutamate receptors are known to depress synaptic transmission by inhibiting transmitter release from presynaptic nerve terminals. This study reports the effects of presynaptic metabotropic glutamate receptor activation on inhibitory synaptic transmission in hypoglossal motoneurons in brainstem slice preparations of neonatal mice. Whole‐cell patch‐clamp recordings were performed on hypoglossal motoneurons of 2–6‐day‐old mice. Monosynaptic glycinergic currents were elicited by electrical stimulation of the nucleus of Roller. Application of the specific metabotropic glutamate receptor agonists (±)‐1‐aminocyclopentane‐trans‐1,3,dicarboxylic acid (t‐ACPD), (2 s,2′r,3′r)‐2‐(2′,3′‐dicarboxylcyclopropyl)‐glycine (DCG‐IV) or l‐2‐amino‐4‐phosphonobutyric acid (L‐AP4) depressed stimulus‐evoked glycinergic inhibitory postsynaptic currents (IPSCs) by an average of 39.5, 59.4 and 39.2%, respectively. In the presence of t‐ACPD, glycinergic miniature IPSCs were reduced in frequency but not in amplitude, which is indicative of a presynaptic mechanism. A similar reduction of IPSC amplitude was observed in the presence of elevated extracellular glutamate or during application of d,l‐threo‐hydroxyaspartate (THA), a blocker of glutamate transport, respectively. The data suggest that uptake of glutamate, which is predominately carried out by glial cells, can prevent spill‐over of glutamate and activation of metabotropic glutamate receptors. A reduction of IPSCs was also observed following application of monofluoroacetic acid, a substance acting specifically on glial cells. Our results suggest that glial regulation of extracellular glutamate uptake can prevent spill‐over of glutamate, and glutamatergic depression of glycinergic inhibition in hypoglossal motoneurons.
Different forms of LTD in the CA1 region of the hippocampus: role of age and stimulus protocol
Authors: Kemp Nicola , McQueen Jane , Faulkes Suzanna , Bashir Zafar I. 
Published: March 2003

AbstractIn this study, we have investigated the developmental range over which different stimulus protocols induce long‐term depression (LTD). Low‐frequency stimulation (LFS; 900 stimuli, 1 Hz) produced LTD in hippocampal slices from rats younger than ∼ 40 days old, but not in animals aged between ∼ 40 days and 16 weeks. We demonstrate, however, that different stimulus protocols can result in LTD in the adult hippocampus. Whilst one paired‐pulse low‐frequency stimulus protocol [PP‐LFS; 50 ms paired‐pulse interval (PPI), 900 pairs of stimuli] produced N‐methyl‐ d‐aspartate (NMDA) receptor‐independent LTD, another PP‐LFS protocol (200 ms PPI; 900 pairs) produced NMDA receptor‐dependent LTD. Furthermore, the saturation of NMDA receptor‐dependent LTD did not prevent the induction of further NMDA receptor‐independent LTD. This lack of occlusion suggests that different mechanisms of expression may underlie each of the above forms of LTD in the adult hippocampus. In contrast to the adult hippocampus, NMDA receptor‐dependent LTD was induced by both LFS and PP‐LFS (50 ms PPI) in slices from young animals (12–20 days). Although they share a common induction mechanism, LTD induced by PP‐LFS may be expressed through other mechanisms in addition to those underlying LFS‐induced LTD in the young hippocampus. In conclusion, the results in this study demonstrate that mechanisms of long‐term synaptic depression within the hippocampus can alter radically with development of the central nervous system and with the use of different induction protocols.
The architecture of the colour centre in the human visual brain: new results and a review *
Authors: Bartels A. , Zeki S. 
Published: March 2003

AbstractWe have used the technique of functional magnetic resonance imaging (fMRI) and a variety of colour paradigms to activate the human brain regions selective for colour. We show here that the region defined previously [Lueck et al. (1989) Nature, 340, 386–389; Zeki et al. (1991) J. Neurosci., 11, 641–649; McKeefry & Zeki (1997) Brain, 120, 2229–2242] as the human colour centre consists of two subdivisions, a posterior one, which we call V4 and an anterior one, which we refer to as V4α, the two together being part of the V4‐complex. The posterior area is retinotopically organized while the anterior is not. We discuss our new findings in the context of previous studies of the cortical colour processing system in humans and monkeys. Our new insight into the organization of the colour centre in the human brain may also account for the variability in both severity and degree of recovery from lesions producing cerebral colour blindness (achromatopsia).
Reversible protein kinase C activation in PC12 cells: effect of NGF treatment
Authors: Dupont Jean‐Luc , Janoshazi Agnes , Bellahcene Mohamed , Mykita Serge , De Barry Jean 
Published: March 2003

AbstractAlthough protein kinase C (PKC) is a key enzyme in the signal transduction process, there is little information on the mechanism leading to PKC activation in living cells. Using a new fluorescence imaging method, we studied this mechanism and correlated PKC conformational changes with intracellular Ca2+ concentration. PC12 cells were simultaneously loaded with Fura‐2‐AM and Fim‐1, two fluorescent probes, which recognize Ca2+ and PKC, respectively. KCl and carbachol (an agonist to muscarinic receptors) applications induced dose‐dependent increases of fluorescence for both probes. Both Ca2+ and PKC responses were observed within seconds following KCl or carbachol application, and were reversible upon stimulus withdrawal. PKC activation kinetics was slightly more rapid than the Ca2+ response after KCl application. After nerve growth factor (NGF) treatment of the cells, the amplitude of the KCl‐induced PKC responses was larger indicating an increase in the activated PKC‐pool in these cells. This difference between control and NGF‐treated cells was not observed following carbachol application, suggesting the involvement of different PKC pools. While the Ca2+ response uniformly occurred in the cytosol, the PKC response displayed a patch pattern with higher intensities in the peripheral zone near the plasma membrane. This heterogeneous distribution of PKC activation sites was similar to the immunocytological localization of Ca2+‐dependent and independent PKC isoforms, which suggested that at least several PKC isoforms interacted with intracellular elements. Upon repeated stimulation, the PKC response rapidly desensitized.
Scale‐invariant superiority of foveal vision in perceptual categorization
Authors: Jüttner Martin , Rentschler Ingo 
Published: March 2003

AbstractThe recognition of objects is exceedingly difficult in indirect view. This complication cannot be explained in terms of retino‐cortical magnification, as size scaling fails to establish position invariance both for character recognition [Strasburger, H. & Rentschler, I. (1996) Eur. J. Neurosci., 8 1787–1791] and pattern classification [Jüttner, M. & Rentschler, I. (1996) Vision Res., 36, 1007–1021]. Thus we compared, for two tasks of discrimination learning and category learning with respect to a common set of grey‐level patterns, how humans perform in foveal and extrafoveal vision. Observers learnt to discriminate (size‐scaled) images equally well in foveal and extrafoveal view, whereas they displayed profound deficiencies in extrafoveal category learning for the same patterns. From the behavioural learning data, internal representations of the learning signals were reconstructed by means of computer simulations. For foveal view, these representations were found to be veridical to their physical counterparts for both learning tasks. For extrafoveal view, they were severely distorted for category learning but not for discrimination learning. A variance reduction of the pattern classes by a factor of 100 reduced the dissociation between extrafoveal categorization and discrimination but did not remove it. These observations suggest a scale‐invariant superiority of foveal vision for learning object categories. This implies a high degree of space variance of visual cognition which is vastly underestimated by classical measures of visual performance, e.g. acuity, visual field and contrast sensitivity.
A novel carboxypeptidase B that processes native β‐amyloid precursor protein is present in human hippocampus
Authors: Matsumoto Akira , Itoh Kyoko , Matsumoto Reiko 
Published: March 2003

AbstractThe processing of β‐amyloid precursor protein (APP) and generation of β‐amyloid (Aβ) are associated with the pathophysiology of Alzheimer's disease (AD). As the proteases responsible for the process in the human brain have yet to be clarified, we have searched for activities capable of cleaving native brain APP in the human hippocampus. A 40‐kDa protein with proteolytic activity that degrades native brain APP in vitro was purified and characterized; molecular analysis identified it as a novel protease belonging to the carboxypeptidase B (CPB) family. PC12 cells overexpressing the cDNA encoding this protease generate a major 12‐kDa β‐amyloid‐bearing peptide in cytosol, a peptide which has also been detected in a cell‐free system using purified brain APP as substrate. Although the protease is homologous to plasma CPB synthesized in liver, it has specific domains such as C‐terminal 14 amino acid residues. Western analysis, cDNA‐cloning process and Northern analysis suggested a brain‐specific expression of this protease. An immunohistochemical study showed that the protease is expressed in various neuronal perikarya, including those of pyramidal neurons of the hippocampus and ependymal‐choroid plexus cells, and in a portion of the microglia of normal brains. In brains of patients with sporadic AD, there is decreased neuronal expression of the protease, and clusters of microglia with protease immunoreactivity associated with its extracellular deposition are detected. These findings suggest that brain CPB has a physiological function in APP processing and may have significance in AD pathophysiology.
Comparison of the selectivity of postsynaptic potentials and spike responses in cat visual cortex
Authors: Volgushev Maxim , Pernberg Joachim , Eysel Ulf T. 
Published: March 2003

AbstractIntracellular recordings were made from neurons in the cat visual cortex (area 17) to compare the orientation and direction selectivities of the output of a cell with those of the input the cell receives. The input to a cell was estimated from the PSPs (postsynaptic potentials) evoked by visual stimulation, and the output estimated from the number of spikes generated during the same responses. For the whole sample, selectivity of the output of cells was significantly higher than selectivity of their input. Upon PSP to spike transformation, the selectivity index was, on average, doubled. However, the degree of the selectivity improvement in individual cells was very different, varying from cases in which highly selective output was created from a poorly selective input and thus selectivity was greatly improved, to little or no improvement in other neurons. The improvement of selectivity was not correlated with resting membrane potential, threshold for action potential generation, background discharge rate or amplitude of optimal PSP response. Further, no systematic difference was found between simple and complex cells in the input–output relations, indicating that the ‘tip of the iceberg’ effect on shaping the response selectivity was cell specific, but not cell type specific. This supports the notion that multiple mechanisms are responsible for generation of the response selectivity, and that the contribution of any particular mechanism may vary from one cell to the other. The heterogeneity of the input–output relations in visual cortical cells could indicate different functions of cells in the cortical network; some cells are creating selectivity de novo, the function of other neurons probably being repetition and amplification of the selected signal and arrangement of the output of a whole column.
Substantia nigra pars reticulata units in 6‐hydroxydopamine‐lesioned rats: responses to striatal D2 dopamine receptor stimulation and subthalamic lesions
Authors: Tseng Kuei Y. , Riquelme Luis A. , Belforte Juan E. , Pazo Jorge H. , Murer M. Gustavo 
Published: March 2003

AbstractIn order to increase our understanding of Parkinson's disease pathophysiology, we studied the effects of intrastriatally administered selective dopamine receptor agonists on single units from the substantia nigra pars reticulata of 6‐hydroxydopamine (6‐OHDA)‐lesioned rats with or without an additional subthalamic nucleus lesion. Nigral pars reticulata units of 6‐OHDA‐lesioned rats were classified into two types, showing regular and bursting discharge patterns, respectively (‘non‐burst’ and ‘burst’ units). Non‐burst and burst units showed distinct responses to intrastriatal quinpirole (the former were excited and burst units inhibited). Furthermore, subthalamic nucleus lesions significantly decreased the number of nigral units showing a spontaneous bursting pattern, and reduced the proportion of units that responded to quinpirole. In contrast, subthalamic lesions did not alter the proportion of nigral units that responded to SKF38393, although the lesions changed some response features, e.g. response type and magnitude. Burst analysis showed that quinpirole did not modify the discharge pattern of burst units, whereas SKF38393 produced a shift to regular firing in 62% of the burst units tested. In conjunction, our results support that: (i) the subthalamic nucleus has an important influence on output nuclei firing pattern; (ii) striatal D2 receptors have a strong influence on nigral firing rate, and a less relevant role in controlling firing pattern; (iii) burst and non‐burst units differ in their response to selective stimulation of striatal dopamine receptors; (iv) the effects of striatal D2 receptors on nigral units are mainly, though not exclusively, mediated by the subthalamic nucleus; and (v) nigral responses to SKF38393 involve the subthalamic nucleus.