bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Orientation Preference Maps in Area 18 of Kitten Visual Cortex
Authors: Gödecke Lmke , Kim Dae‐Shik , Bonhoeffer Tobias , Singer Wolf 
Published: April 2006

AbstractWe investigated the development of orientation preference maps in the visual cortex of kittens by repeated optical imaging from the same animal. Orientation maps became detectable for the first time around postnatal day (P) 17 and improved continuously in strength until P30, the time at which their appearance became adult‐like. During this developmental period the overall geometry of the maps remained unchanged, suggesting that the layout of the orientation map is specified prior to P17. Hence, before the visual cortex becomes susceptible to experience‐dependent modifications its functional architecture is largely specified. This suggests that the initial development and layout of orientation preference maps are determined by intrinsic processes that are independent of visual experience. This conclusion is further supported by the result that orientation maps were well expressed at P24 in binocularly deprived kittens. Because the appearance of the first orientation‐selective neurons and the subsequent development of orientation preference maps correlated well with the time course of the expression and refinement of clustered horizontal connections, we propose that these connections might contribute to the specification of orientation preference maps.
Up‐regulation of Bax Protein in Degenerating Retinal Ganglion Cells Precedes Apoptotic Cell Death after Optic Nerve Lesion in the Rat
Authors: Isenmann Stefan , Wahl Claudia , Krajewski Stanislaw , Reed John C. , Bähr Mathias 
Published: April 2006

AbstractRetrograde degeneration of retinal ganglion cells as a consequence of optic nerve lesion has been shown to fulfil the criteria of apoptosis. In the present study, we investigated the time course of ganglion cell apoptosis following intraorbital crushing of the optic nerve in adult rats using morphological criteria and applying a terminal transferase technique (TUNEL) for in situ detection of DNA strand breaks. In addition, we examined expression patterns of the anti‐apoptotic proteins Bcl‐2 and Bcl‐X and the cell death‐promoting protein Bax in retinae after crushing the optic nerve. Apoptotic nuclei were detected in the ganglion cell layer in the first 3 weeks after optic nerve crush, with a peak after 6 days. Bcl‐2 and Bcl‐X proteins were expressed in ganglion cells at low levels. Expression of Bcl‐2 decreased further during the days following crush. Bcl‐X expression was initially increased, followed by a decline over the following days. In contrast, Bax protein, which was expressed in most ganglion cells at moderate baseline levels, was sharply increased as early as 30 min after crush, reached peak levels after 3 days, and remained up‐regulated for at least 1 week thereafter. Double labelling for Bax and TUNEL in retinal sections, however, did not reveal colocalization of the two signals in individual retinal ganglion cells, consistent with the idea that increases in Bax precede apoptosis after optic nerve lesion. Thus, retinal ganglion cell death might be prevented by ablation of Bax protein in these cells, or by up‐regulation of Bax‐antagonists such as Bcl‐2 or Bcl‐X.
Chronic Loss of Glucocorticoids Following Adrenalectomy Down‐regulates the Expression of Glucocorticoid Receptor mRNA in the Rat Forebrain
Authors: Hu Zhongting , Yuri Kazunari , Morimoto Masafumi , Ozawa Hitoshi , Kawata Mitsuhiro 
Published: April 2006

AbstractIn the negative feedback model, loss of endogenous glucocorticoids up‐regulates the expression of glucocorticoid receptor mRNA. To elucidate further the effect of chronic lack of glucocorticoids on the expression of glucocorticoid receptor mRNA and protein, in situ hybridization and immunohistochemical methods were used to examine the long‐term alteration of glucocorticoid receptor mRNA and its immunoreactivity in the forebrain of adrenalectomized rats. Constant lack of glucocorticoids resulted in marked decrease in the expression of glucocorticoid receptor mRNA and disappearance of glucocorticoid receptor immunoreactivity in many forebrain structures. In particular, in the suprapyramidal blade of the hippocampal granule cell layer and cerebral cortex, many cells showed almost no glucocorticoid receptor mRNA signals. These results suggest that long‐term loss of endogenous glucocorticoids down‐regulates the levels of glucocorticoid receptor mRNA, leading to reduction in the synthesis of glucocorticoid receptors in the rat forebrain. Therefore, the presence of endogenous glucocorticoids is vital to the continued expression of glucocorticoid receptor mRNA.
Spatial View Cells in the Primate Hippocampus
Authors: Rolls Edmund T. , Robertson Robert G. , Georges‐François Pierre 
Published: April 2006

AbstractHippocampal function was analysed by making recordings in rhesus monkeys actively walking in the laboratory. In a sample of 352 cells recorded in the hippocampus and parahippocampal cortex, a population of ‘spatial view’ cells was found to respond when the monkey looked at a part of the environment. The responses of these hippocampal neurons (i) occur to a view of space ‘out there’, not to the place where the monkey is, (ii) depend on where the monkey is looking, as shown by measuring eye position, (iii) do not encode head direction, and (iv) provide a spatial representation that is allocentric, i.e. in world coordinates. This representation of space ‘out there’ would be an appropriate part of a primate memory system involved in memories of where in an environment an object was seen, and more generally in the memory of particular events or episodes, for which a spatial component normally provides part of the context.
Critical Role for M3 Muscarinic Receptors in Paradoxical Sleep Generation in the Cat
Authors: Sakai Kazuya , Onoe Hirotaka 
Published: April 2006

AbstractIn the cat, microdialysis application of 200 μM carbachol to the peri‐locus coeruleus a (peri‐LCα) of the mediodorsal pontine tegmentum produced a marked (≤5–fold) increase in paradoxical sleep. This effect was blocked by 5–50 μM 4–diphenylacetoxy‐N‐methylpiperidine methiodide (4–DAMP), an M1/M3‐selective muscarinic receptor antagonist. In contrast, the effect was not reversed by methoctramine, an M2‐selective antagonist, or pirenzepine, an M1‐selective antagonist, even at concentrations as high as 500 μM. In addition, unilateral application of 5 μM 4–DAMP alone to the peri‐LCa induced both a >60% decrease in paradoxical sleep and a state of paradoxical sleep without atonia, whereas 50 μM pirenzepine and 500 μM methoctramine had no effect. Our findings are further evidence for the important role played by the peri‐LCα and demonstrate a critical role for M3 muscarinic cholinergic receptors in the generation of paradoxical sleep.
Persistent Excitability Changes in the Piriform Cortex of the Isolated Guinea‐pig Brain after Transient Exposure to Bicuculline
Authors: Forti Matteo , Biella Gerardo , Caccia Silvio , de Curtis Marco 
Published: April 2006

AbstractThe development of long‐lasting excitability changes after a single intracerebral injection1 of bicuculline (1 mM) in a restricted region of the anterior piriform cortex was studied by means of simultaneous, intra‐ and extracellular recordings in the isolated guinea‐pig brain preparation maintained in vitro by arterial perfusion. The transitory disinhibition induced by bicuculline revealed transient afterdischarges that were followed˜ by the activation of a synaptic potential mediated by the recurrent propagation of the focal epileptiform activity along cortico‐cortical associative fibres. The epileptiform associative potential persisted for the duration of the1 experiment. Both the induction and the long‐term expression of the epileptiform associative potential were dependent on the activation of glutamatergic receptors of the NMDA type, as demonstrated by perfusion with the NMDA receptor antagonist 2–aminopentanoic acid (AP5) (100 μM). After bicuculline washout, piriform cortex neurons responded to afferent stimulation with a burst discharge superimposed on a paroxysmal depolarizing potential. The early component of the burst was mediated by a Ca2+‐dependent, non‐synaptic potential located at the proiimal apical dendrites and soma of layer 11–111 cells, since (i) it was abolished by membrane hyperpolarization, (ii) it was not affected by AP5, (iii) it was correlated with a current sink in layer II, as demonstrated by current source density analysis of field potential laminar profiles, and (iv) it was abolished by cadmium (2–5 mM) applied lbcally in layer II. The late component of the burst response (i) coincided in time with the extracellular epileptiform hssociative potential, (ii) increased linearly in amplitude during membrane hyperpolarization, (iii) was blocked by AP5, and (iv) was correlated with an extracellular sink in layer Ib, where the associative fibres contact the distal apical dendrites of piriform cortex neurons. The results presented here indicate that a transient focal disinhibition promotes persistent intrinsic and synaptic excitability changes in piriform cortex neurons. These changes may be responsible for the propagation of epileptiform activity and for the induction of secondary epileptogenesis.
An Evolutionarily Conserved Region in the Second lntron of the Human Nestin Gene Directs Gene Exmession to CNS Progenitor Cells and to Early Neural Ciest Cells
Authors: Lothian Carina , Lendahl Urban 
Published: April 2006

AbstractCentral nervous system (CNS) progenitor cells transiently proliferate in the embryonic neural tube and give rise to neurons and glial cells. A characteristic feature of the CNS progenitor cells is expression of the intermediate filament nestin and it was previously shown that the rat nestin second intron functions as an enhancer, directing gene expression to CNS progenitor cells. In this report we characterize the nestin enhancer in further detail. Cloning and sequence analysis of the rat and human nestin second introns revealed local domains of high sequence similarity in the 3′ portion of the introns. Transgenic mice were generated with the most conserved 714 bp in the 3′ portion of the intron, or with the complete, 1852 bp, human second intron, coupled to the reporter gene lacZ. The two constructs gave a very similar nestin‐like expression pattern, indicating that the important control elements reside in the 714 bp element. Expression was observed starting in embryonic day (E)7.5 neural plate, and at E10.5 CNS progenitor cells throughout the neural tube expressed lacZ. At E12.5, lacZ expression was more restricted and confined to proliferating regions in the neural tube. An interesting difference, compared to the rat nestin second intron, was that the human intron at E10.5 mediated lacZ expression also in early migrating neural crest cells, which is a site of endogenous nestin expression. In conclusion, these data show that a relatively short, evolutionarily conserved region is sufficient to control gene expression in CNS progenitor cells, but that the same region differs between rodents and primates in its capacity to control expression in neural crest cells.
Neuronal GDNF Expression in the Adult Rat Nervous System Identified By In Situ Hybridization
Authors: Pochon N. A.‐M. , Menoud A. , Tseng J. L. , Zurn A. D. , Aebischer P. 
Published: April 2006

AbstractGlial cell line‐derived neurotrophic factor (GDNF) is a potent neurotrophic factor which has been purified on the basis of its ability to promote the survival of dopaminergic neurons in vitro. GDNF has subsequently been cloned and its sequence shown to be distantly related to transforming growth factor‐β (TGF‐β). To identify GDNF expressing cells in the adult rat brain, in situ hybridization using a digoxygenin (DIG)‐labelled riboprobe has been performed. Our results show that GDNF mRNA is mainly expressed in neurons and that its synthesis is not restricted to dopaminergic areas. It is widely expressed in the cortex, the hippocampus, the striatum, the substantia nigra, the thalamus, the cerebellum and the spinal cord. Neuronal GDNF expression varies among brain regions as determined by the intensity of the in situ signal. Double labelling of the substantia nigra using tyrosine hydroxylase immunohistochemistry, associated with GDNF in situ hybridization, show that the majority of dopaminergic neurons express GDNF. The widespread expression of GDNF throughout the adult brain suggests that its administration in Parkinson's disease should be restricted to the altered structures, in order to avoid possible deleterious side effects.
Increased Presynaptic Protein Kinase C Activity and Glutamate Release in Rats with a Prenatally Induced Hippocampal Lesion
Authors: Di Luca M. , Caputi A. , Cattabeni F. , De Graan P. N. E. , Gispen W. H. , Raiteri M. , Fassio A. , Schmid G. , Bonanno G. 
Published: April 2006

AbstractWe have previously shown that protein kinase C (PKC) activity is up‐regulated in nerve terminals of animals that have been subjected to targeted cellular ablation of cortical and hippocampal neurons by treatment with methylazoxymethanol (MAM), which results in impaired long‐term potentiation (LTP) and cognitive deficit. In this study we investigated the consequences of increased membrane‐bound PKC in the regulation of release of glutamate, the major excitatory transmitter involved in LTP. We show that nerve terminals of MAM‐treated rats show higher PKC activity, as monitored by the in situ phosphorylation of B‐50/GAP‐43, in both basal and phorbol ester‐stimulated conditions. In these animals, hippocampal nerve endings release a greater amount of glutamate than those of controls, both in basal conditions and when synaptosomes are stimulated with KCI or 3,4–diaminopyridine. The potentiation observed in MAM‐treated rats was counteracted by the PKC blocker H‐7 and the clostridial tetanus toxin. On the contrary, GABA release was not significantly up‐regulated, either in basal or in depolarization‐evoked conditions. Therefore our data show that the increase in synaptosomal PKC activity is paralleled by increased glutamate but not GABA release in this animal model. Whether this reflects specific up‐regulation of membrane PKC activity in glutamatergic terminals or an alteration in the regulation of glutamate release remains to be determined.
Tenascin‐C Synthesis and Influence on Axonal Growth During Rat Cortical Development
Authors: Götz Magdalena , Bolz Jürgen , Joester Angret , Faissner Andreas 
Published: April 2006

AbstractSeveral putative guidance molecules are restricted to the marginal and subplate zones, the major fibre tracts in the developing cortex. It is presently unknown how their distribution is achieved and how these molecules affect neurite extension. Tenascin‐C is of particular interest in this context, because it may either promote or deflect growing axons depending on its mode of presentation. Therefore, the cellular origin of tenascin‐C in the developing rat cortex and its effects on the extension of cortical afferents and efferents were examined. Tenascin‐C protein is first restricted to the marginal and subplate zones and spreads later into the developing grey matter, in close correlation with afferent innervation. In situ hybridization showed that tenascin‐C mRNA is first confined to the ventricular zone, at some distance from the location of the protein, while at later stages tenascin‐C‐synthesizing cells become scattered throughout the cortical thickness, concomitant with the spread of the protein. In order to assess its function, monoclonal antibodies directed against different domains of tenascin‐C were used in quantitative axonal outgrowth assay. These perturbation experiments suggested that distinct tenascin‐C fibronectin type 111 repeats sustain the growth of thalamic and cortical axons on cortical membrane carpets, whereas the EGF‐type repeats are not involved. The combination of different antibodies revealed that separate fibronectin‐type III repeats exert cooperative effects. These results suggest that ventricular zone cells regulate the establishment of thalamic and cortical axonal projections through locally restricted deposition of tenascin‐C.
Anatomical Gradients in Proliferation and Differentiation of Embryonic Rat CNS Accessed by Buoyant Density Fractionation: α3, β3 and γ2 GABAA Receptor Subunit Co‐expression by Post‐mitotic Neocortical Neurons Correlates Directly with Cell Buoyancy
Authors: Maric Dragan , Maric Irina , Ma Wu , Lahojuji Fatiha , Somogyi Roland , Wen Xiling , Sieghart Werner , Fritschy Jean‐Marc , Barker Jeffery L. 
Published: April 2006

AbstractDevelopment of the CNS occurs as complex cascade of pre‐programmed events involving distinct phases of cell proliferation and differentiation. Here we show these phases correlate with cells of specific buoyant densities which can be readily accessed by density gradient fractionation. Sprague‐Dawley dams were pulse‐labelled with bromodeoxyuridine (BrdU) and selected regions of embryonic (E) CNS tissues at El1–22 dissociated with papain into single‐cell suspensions. Proliferative cell populations were assessed by anti‐BrdU and propidium iodide staining using flow cytometry. Cell differentiation was evaluated using molecular and immunocytochemical probes against mRNAs and antigens differentiating the neuroepithelial, neuronal and glial cell lineages. The results show the emergence of distinctive spatiotemporal changes in BrdU+ populations throughout the CNS during embryonic development, which were followed by corresponding changes in the cellular distributions of antigens distinguishing specific cell types. Fractionation of neocortical cells using discontinuous Percoll gradients revealed that an increasing number of cells increase their buoyancy during corticogenesis. Immunocytochemical and molecular characterization showed that the proliferative and progenitor cell populations are for the most part associated with lower buoyancy or higher specific buoyant densities (> 1.056 g/ml) whereas the post‐mitotic, differentiated neurons generally separated into fractions of higher buoyancy or lower specific buoyant densities (<1.043 g/ml). Immunostaining with antibodies against several GABAA receptor subunits (α3, β3, γ2) revealed that the highest percent (70–90%) of immunopositive cells could be identified in the most buoyant, differentiating neurons found in the cortical plate/subplate regions, with the lowest percent of the immunopositive cells found in the least buoyant, proliferative and progenitor cell populations originating from the ventricular/subventricular zones. Taken together, these results indicate that buoyant density is distinguishing characteristic of embryonic CNS cells transforming from primarily proliferative to mainly differentiating, and that fractionation of these cells according to their buoyant densities provides rapid access to the properties of specific cell lineages during the prenatal period of CNS development.
Dendritic Localization of Rat Vasopressin mRNA: Ultrastructural Analysis and Mapping of Targeting Elements
Authors: Prakash Nilima , Fehr Susanne , Mohr Evita , Richter Dietmar 
Published: April 2006

AbstractTranscripts encoding the vasopressin precursor are located in axons and dendrites of rat hypothalamic magnocellular neurons. While the axonal vasopressin mRNA has been extensively characterized both at the biochemical and morphological level, little is known about those transcripts residing in dendrites of magnocellular neurons. As revealed by in situ hybridization at the electron microscopic level, the mRNA is located in proximal and distal dendritic segments and is exclusively confined to regions containing rough endoplasmic reticulum. These results suggest that dendrites of hypothalamic neurons may be capable of local precursor synthesis independent of that occurring in the cell somata. A heterologous system has been employed to define cis‐acting elements within the vasopressin mRNA which may be involved in dendritic compartmentalization. Expression vector constructs consisting of the cytomegalovirus promoter coupled to the rat vasopressin cDNA have been injected into the cell nuclei of cultured neurons derived from embryonic rat superior cervical ganglia. Vector‐encoded vasopressin transcripts were also sorted to dendrites of these neurons indicating that the molecular determinants of dendritic mRNA transport are not cell specific. Mapping of the targeting elements revealed two segments within the vasopressin mRNA that are able to confer dendritic compartmentalization to α‐tubulin mRNA which is normally confined to the cell body.
The Neural Correlates of the Noradrenergic Modulation of Human Attention, Arousal and Learning
Authors: Coull J. T. , Frith C. D. , Dolan R. J. , Frackowiak R. S. J. , Grasby P. M. 
Published: April 2006

AbstractThe prefrontal cortex has been suggested as a site of action for the noradrenergic modulation of cognition. In healthy volunteers attentional deficits can be induced by the α2 adrenoceptor agonist clonidine, without impairment of more explicit tests of frontal lobe function. It is therefore possible that the effects of noradrenaline cannot be localized to a specific brain area such as the prefrontal cortex, but instead involve structures in a more widespread attentional network. A 1.5 μg/kg dose of clonidine or placebo was administered to 13 healthy male volunteers performing the rapid visual information processing task, which places demands on both sustained attention and working memory. Twelve positron emission tomography measurements of regional cerebral blood flow (rCBF) were collected during performance of this task and also during a rest state. A second experiment in 12 healthy volunteers examined the effects of a 1.3 μg/kg dose of clonidine on the rCBF changes associated with performance of a paired associates learning task compared with passive listening to word pairs. Comparison of each of the experimental tasks with its respective control replicated previous findings. A significant drug × task interaction, common to the two studies, was found in the right thalamus. Inspection of the adjusted rCBF values showed that the effect was due to attenuation of thalamic rCBF during the control states rather than to any effects of clonidine during performance of the cognitive tasks, although the effect was stronger in the rapid visual information processing study than in the paired associates learning study. The significant effect of clonidine during the control as opposed to the ‘cognitive’ activation state is consistent with previous findings in animals and humans demonstrating greater effects of clonidine during states of relatively low arousal. The results suggest neuroanatomical dissociation of the noradrenergic modulation of arousal (via the thalamus) and attention.
Follicular Tissues Reduce Drug Effects on Ion Channels in Oocytes of Xenopus laevis
Authors: Madeja Michael , Musshoff Ulrich , Speckmann Erwin‐Josef 
Published: April 2006

AbstractThe influence of follicular tissues on drug effects on ion channels in Xenopus oocytes was tested by investigating the pharmacological properties of a cloned potassium channel in oocytes with and without follicular tissues. The data show that the efficacy of blocking agents (ranging from metal ions to peptides) is drastically reduced by the follicular tissues (reductions by as much as 90% and increases of the IC50 values up to 30–fold). Furthermore, the time course of the blocking effect was slowed down by the tissues (increases of the t50 values up to 40–fold). The described impairment could be mitigated, but not abolished by partial removal of the follicular tissues (so‐called defolliculation, leaving only the vitelline envelope and part of the follicle cells on the oocyte surface). The results indicate that the follicular tissues can induce significant errors in pharmacological measurements on membrane proteins in Xenopus oocytes.