bluuebunny/crossref_metadata_2025_split huggingface dataset:
Somatotopy in the Human Motor Cortex Hand Area. A High‐Resolution Functional MRI Study
Authors: Kleinschmidt Andreas , Nitschke Matthias F. , Frahm Jens 
Published: April 2006

AbstractFine‐scale somatotopic encoding in brain areas devoted to sensorimotor processing has recently been questioned by functional neuroimaging studies which suggested its absence within the hand area of the human primary motor cortex. We re‐examined this issue by addressing somatotopy both in terms of functional segregation and of cortical response preference using oxygenation‐sensitive magnetic resonance imaging at high spatial resolution. In a first step, spatial representations of self‐paced isolated finger movements were mapped by using motor rest as a control state. A subsequent experimental design studied the predominance of individual finger movements by using contrasting finger movements as the control task. While the first approach confirmed previous reports of extensive overlap in spatial representations, the second approach revealed foci of differential activation which displayed an orderly mediolateral progression in accordance with the classical cortical motor homunculus. We conclude that somatotopy within the hand area of the primary motor cortex does not present as qualitative functional segregation but as quantitative predominance of certain movement or digit representation embedded in an overall joint hand area.
Differential Modulation of the Uptake Currents by Redox Interconversion of Cysteine Residues in the Human Neuronal Glutamate Transporter EAAC1
Authors: Trotti Davide , Nussberger Stephan , Volterra Andrea , Hedger Matthias A. 
Published: April 2006

AbstractControl of extrasynaptic glutamate concentration in the central nervous system is an important determinant of neurotransmission and excitotoxicity. Mechanisms that modulate glutamate transporter function are therefore critical factors in these processes. The redox modulation of glutamate uptake was examined by measuring transporter‐mediated electrical currents and radiolabelled amino acid influx in voltage‐clamped Xenopus oocytes expressing the human neuronal glutamate transporter EAAC1. Up and down changes of the glutamate uptake currents in response to treatment with dithiothreitol and 5,5′‐dithio‐bis‐(2‐nitrobenzoic) acid (DTNB) were observed in oocytes clamped at ‐60 mV. The redox interconversion of cysteines induced by dithiothreitol/DTNB influenced the Vmax (Imax) of transport, while the apparent affinity for glutamate was not affected. Formation or breakdown of disulphide groups did not affect the pre‐steady‐state currents, suggesting that these manipulations do not interfere with the Na+ binding/unbinding and/or the charge distribution on the transporter molecule. The glutamate‐evoked net uptake current of EAAC1 was composed of the inward current from electrogenic glutamate transport and the current arising from the glutamate‐activated CI‐ conductance. The structural rearrangement produced by the formation or breakdown of disulphide groups only affected the current from electrogenic giutamate transport. The electrogenic currents of EAAC1 were significantly reduced by peroxynitrite, an endogenously occurring oxidant formed in certain pathological brain processes, and the mechanism of inhibition partially depended on the formation of disulphide groups.
Complexities in the Thalamocortical and Corticothalamic Pathways
Authors: Adams Niels C. , Lozsádi Dora A. , Guillery R. W. 
Published: April 2006

AbstractIt is now a century since Kölliker (Handbuch der Gewebelehre des Menschen. Nervensystemen des Menschen und der Thiere, Vol. 2, 6th edn. Engelmann, Leipzig, 1896) described the thalamic reticular nucleus as the ‘Gitterkern’ or lattice nucleus on the basis of the fibrous latticework that is the characteristic feature of this part of the ventral thalamus and adjacent parts of the internal capsule. We suggest that the fibre reorganization produced in this lattice is a fundamental requirement for linking orderly maps in the thalamus to corresponding cortical maps by two‐way thalamocortical and corticothalamic connections; these connections involve divergence, convergence and mirror reversals, which all have to occur between the thalamus and the cortex. Apart from the thalamic reticular nucleus, two transient groups of cells, the perireticular nucleus (located in the internal capsule lateral to the reticular nucleus) and the cells of the cortical subplate, are prominent along the course of axons linking the cortex and thalamus early in development. The functions of these two cell groups are not known. However, since early in development complex patterns of reorganization, defasciculation and crossings occur in the regions of these cells, it is likely that they play a role in creating the latticework of the adult. The latticework that characterizes the thalamic reticular nucleus of mammals can also be identified in the ventral thalamus of non‐mammalian brains, formed along the course of the fibres that join the dorsal thalamus to the telencephalon. We suggest that the ubiquitous presence of such a zone of fibre reorganization is integral to the functioning of the thalamocortical pathways, and that the complexity of thalamic connections produced in the lattice has been central to the evolutionary success of the thalamotelencephalic system.
Infusions of Tyrosine Hydroxylase Antisense Oligodeoxynucleotide into Substantia Nigra of the Rat: Effects on Tyrosine Hydroxylase mRNA and Protein Content, Striatal Dopamine Release and Behaviour
Authors: Skutella Thomas , Schwarting Rainer K. W. , Huston Joseph P. , Sillaber Lnge , Probst Joseph C. , Holsboer Florian , Spanagel Rainer 
Published: April 2006

AbstractModulation of the transcriptional message of tyrosine hydroxylase was investigated in vivo in the rat nigrostriatal dopamine system with unmodified antisense oligodeoxynucleotide, mismatch oligodeoxynucleotide or vehicle controls. Oligodeoxynucleotide was infused (0.5 μg/0.5 μl/h) unilaterally into the substantia nigra by an osmotic minipump system over 14 days. The presence of oligodeoxynucleotide in the brain was verified by in situ hybridization and fluorescence labelling. Animals treated with unmodified antisense oligodeoxynucleotide showed ipsilateral turning behaviour when challenged systemically with the indirect dopamine agonist amphetamine, whereas mismatch‐ and vehicle‐infused rats showed no such behavioural asymmetries. In the substantia nigra, antisense treatment had no effects on tyrosine hydroxylase mRNA, but it led to a reduction in tyrosine hydroxylase protein content. Tissue levels of dopamine, measured in postmortem tissue punches of the neostriatum and substantia nigra, were reduced in the oligodeoxynucleotide‐treated hemisphere. Furthermore, basal extracellular levels of dopamine, monitored by in vivo microdialysis, were also lower in the neostriatum ipsilateral to antisense infusion and showed a weaker response to an amphetamine challenge when compared with the contralateral side. These effects were not observed after infusion of mismatch oligodeoxynucleotide or vehicle into the substantia nigra. Finally, the GABAergic enzyme glutamate decarboxylase was not affected in the antisense‐treated substantia nigra, indicating that non‐specific damage in this area was not caused by this treatment. Our results indicate that antisense oligodeoxynucleotide treatment against tyrosine hydroxylase in the substantia nigra has behavioural and neurochemical effects that are comparable with known actions of dopamine neurotoxins, which are conventional pharmacological tools for the depletion of dopamine. Furthermore, our data show the potential of antisense targetting to reveal new relationships between neurotransmitter‐related enzymes and behavioural parameters, because the possibility of selectively and discretely manipulating tyrosine hydroxylase function is likely to produce new insights into the physiological and behavioural functions of the dopaminergic nigrostriatal system.
Organization of Pyramidal Cell Apical Dendrites and Composition of Dendritic Clusters in the Mouse: Emphasis on Primary Motor Cortex
Authors: Lev Dmitri L. , White Edward L. 
Published: April 2006

AbstractIt has been proposed that neurons in sensory cortices are organized into modules that centre on clusters of apical dendrites belonging to layer V pyramidal neurons. In the present study, sections reacted for microtubule‐associated protein (MAPP) were examined in order to determine the three‐dimensional inter‐relationships of pyramidal cell dendrites in mouse primary motor cortex (MsI) cortex. Results indicate that pyramidal cell dendrites in MsI cortex can be interpreted to be arranged in a modular fashion, and that these modules are organized similarly to those in the sensory areas of the cortex. Also included in the present study are experiments designed to determine if the clusters of apical dendrites, around which the modules are centred, are composed of dendrites belonging to one or to more than one type of projection cell. Callosal neurons in MsI cortex were labelled by the retrograde transport of horseradish peroxidase deposited onto severed callosal fibres in the contralateral hemisphere. Examination of tangential thin sections through layer IV of MsI cortex shows clusters of apical dendrites in which every dendrite is labelled with horseradish peroxidase. Adjacent clusters are composed of unlabelled dendrites, suggesting that the apical dendrites of callosal neurons aggregate to form clusters that are composed exclusively of dendrites belonging to this type of projection cell. These findings suggest a hitherto unsuspected degree of specificity in the cellular composition of cortical modules.
Corticotropin‐releasing Factor in the Caudal Pontine Reticular Nucleus Mediates the Expression of Fear‐potentiated Startle in the Rat
Authors: Fendt Markus , Koch Michael , Schnitzler Hans‐Ulrich 
Published: April 2006

AbstractThe fear‐potentiated startle paradigm is a valuable model for the investigation of the neuronal basis of fear. Previous studies have demonstrated that the neuropeptide corticotropin‐releasing factor (CRF) plays an important role in fear‐related processes, notably in the potentiation of the acoustic startle response. The present study investigated the role in fear‐potentiated startle of CRF in the caudal pontine reticular nucleus, a brain nucleus that mediates the acoustic startle response. First, we showed that the central nucleus of the amygdala gives rise to a CRFergic projection to the caudal pontine reticular nucleus. In the second experiment, we iontophoretically applied CRF to caudal pontine reticular nucleus neurons and extracellularly recorded the activity of these neurons. CRF had a mainly excitatory effect on the tone‐evoked activity of the neurons. In our third experiment, we injected the CRF antagonist α‐helical CRF into the caudal pontine reticular nucleus of awake rats. Here, α‐helical CRF dose‐dependently blocked fear‐potentiated startle, but had no effect on the baseline startle amplitude. The present results show that CRF‐containing neurons which project from the central nucleus to the caudal pontine reticular nucleus are important for the enhancement of startle by fear, and further characterize the hypothetical neuronal circuitry underlying the expression of fear‐potentiated startle.
GP55 Inhibits both Cell Adhesion and Growth of Neurons, but not Non‐neuronal Cells, via a G‐protein‐coupled Receptor
Authors: Clarke G. A. , Moss D. J. 
Published: April 2006

AbstractThere is compelling evidence for the role of inhibitory molecules in guiding neurons to their appropriate targets. Furthermore, continued expression of these molecules in the adult could explain why there is little regeneration of neurons in the central nervous system. We have previously identified a family of glycosyl phosphatidylinositol‐linked glycoproteins (GP55) from adult chicken brain that has been shown to inhibit neurite outgrowth from dorsal root ganglion and forebrain neurons. GP55 consists of two or more glycoproteins and belongs to a subgroup of the Ig superfamily which contains OBCAM, LAMP, neurotrimin and CEPU‐1. We now show that GP55 is anti‐adhesive, blocking the adhesion of neurons to normally adhesive substrata in a concentration dependent manner. The anti‐adhesive effect can be blocked using antiserum raised against GP55 and pertussis toxin (PTX) but not the β oligomer alone. In contrast, the adhesion of fibroblasts and Schwann cells to the substrata is not affected by GP55. Indeed, non‐neuronal cells spread and grow normally. These results would suggest that both the anti‐adhesive effect and the inhibition of outgrowth by GP55 is specific to neurons and is mediated by a PTX sensitive, G‐protein‐coupled receptor.
Differential Effects of Acetylcholine on Neuronal Activity and Interactions in the Auditory Cortex of the Guinea‐pig
Authors: Shulz Daniel E. , Cohen Shuki , Haidarliu Sebastian , Ahissar Ehud 
Published: April 2006

AbstractDuring normal brain operations, cortical neurons are subjected to continuous cholinergic modulations. In vitro studies have indicated that, in addition to affecting general cellular excitability, acetylcholine also modulates synaptic transmission. Whether these cholinergic mechanisms lead to a modulation of functional connectivity in vivo is not yet known. Herein, the effects were studied of an iontophoretic application of acetylcholine and of the muscarinic agonist, carbachol, on the ongoing activity and co‐activity of neurons simultaneously recorded in the auditory cortex of the anaesthetized guinea‐pig. Iontophoresis of cholinergic agonists mainly affected the spontaneous firing rates of auditory neurons, affected autocorrelations less (in most cases their central peak areas were reduced), and rarely affected cross‐correlations. These findings are consistent with cholinergic agonists primarily affecting the excitability of cortical neurons rather than the strength of cortical connections. However, when changes of cross‐correlations occurred, they were usually not correlated with concomitant changes in average firing rates nor with changes in autocorrelations, which suggests a secondary cholinergic effect on specific cortico‐cortical or thalamo‐cortical connections.
Regulation of Quantal Transmitter Secretion by ATP and Protein Kinases at Developing Neuromuscular Synapses
Authors: Fu W. M. , Chen Y. H. , Lee K. F. , Liou J. C. 
Published: April 2006

AbstractThe effects of endogenously released ATP on the maturation of developing neuromuscular synapses were investigated in Xenopus nerve‐muscle co‐cultures. The potentiating action of ATP (1 mM) on spontaneous acetylcholine release was inhibited by P2‐purinoceptor antagonists suramin (0.3 mM) and reactive blue 2 (RB‐2, 3 μM) in day 1 cultures. Bath application of suramin (10 μM) or RB‐2 in day 1 cultures and prolonged treatment for 2 days dramatically decreased the amplitude of both spontaneous synaptic currents (SSCs) and evoked synaptic currents (ESCs) in the same cultures on day 3. Chronic treatment with 8‐cyclopentyltheophylline (4 μM) or 6‐cyano‐2, 3‐dihydroxy‐7‐nitroquinoxaline (CNQX, 10 μM), P1‐purinoceptor and glutamate receptor antagonists respectively, did not exert such an inhibitory effect. Chronic treatment with suramin or RB‐2 for 2 days had no significant effect on the amplitude of either iontophoretic acetylcholine‐induced whole‐cell currents or single acetylcholine channel measurements in 3‐day‐old cultured myocytes. In addition, prolonged treatment for 2 days with various kinase inhibitors such as H‐8 (10 μM), KN‐62 (5 μM) and H‐7 (10 μM) also decreased the amplitudes of both spontaneous and evoked synaptic currents in natural synapses, but not those of iontophoretic acetylcholine‐induced currents. Furthermore, suramin and these protein kinase inhibitors also decreased the amplitude of spontaneous synaptic currents in manipulated synapses of ‘vacated’ nerve terminals. The results suggest that endogenously released ATP, acting in concert with various protein kinases, is involved in the maintenance and/or development of the quantum size of synaptic vesicles at embryonic neuromuscular synapses.
Activation by Cutaneous or Visceral Noxious Stimulation of Spinal Neurons Projecting to the Medullary Dorsal Reticular Nucleus in the Rat: A c‐fos Study
Authors: Almeida Armando , Lima Deolinda 
Published: April 2006

AbstractThe involvement of spinal neurons in the transmission of cutaneous and visceral nociceptive input to the medullary dorsal reticular nucleus was studied. Rats were injected with cholera toxin subunit B in the left dorsal reticular nucleus and subjected 4 days later to noxious mechanical, thermal or chemical stimulation of the proximal internal aspect of the left thigh, or to chemical stimulation of the urinary bladder. Sections of spinal segments T13‐L3 were processed immunocytochemically for cholera toxin subunit B and Fos protein. The percentage of double‐labelled cells in the population of Fos‐positive cells was higher in lamina I (1–4%) than in deeper laminae (0–0.7%) following all stimuli. The percentage of double‐labelled cells in the population of retrogradely labelled cells was 30–53% in lamina I and 0–5% in laminae III—X. Visceral stimulation activated more retrogradely labelled lamina I cells than any kind of cutaneous stimulation. Pyramidal cells were activated in higher numbers than multipolar and flattened cells after thermal cutaneous or visceral stimulation, and in lower numbers than multipolar cells after mechanical stimulation. These results suggest that, in the experimental conditions used, spinal cord cells conveying noxious input to the dorsal reticular nucleus are concentrated in lamina I. They further indicate that the spinaldorsal reticular nucleus pathway plays a major role in the transmission of nociceptive visceral input, and point to the preferential involvement of pyramidal cells in cutaneous thermal and visceral processing.
Locomotor‐Related Presynaptic Modulation of Primary Afferents in the Lamprey
Authors: El Manira A. , Tegner J. , Grillner S. 
Published: April 2006

AbstractPresynaptic modulation of sensory afferent transmission during rhythmic motor activity was investigated in the lamprey spinal cord in vitro. Intracellular recordings were performed from the somata and axons of the glutamatergic sensory neurons from the skin (dorsal cells) during locomotor activity induced by N‐methyl‐D‐aspartate (NMDA). Dorsal cells were phasically depolarized during each ipsilateral ventral root burst. In some soma recordings no or only small amplitude depolarizations were seen, although intracellular recording of their axons revealed the existence of large depolarizations, suggesting that the input synapses are located on the axons. The amplitude of the depolarizations increased during intracellular injection of hyperpolarizing current. The amplitude of the depolarizations increased when the frequency of the locomotor rhythm was increased by elevating the NMDA concentration. The depolarizations were not blocked by specific GABAA (bicuculline) or GABAB (phaclofen and saclofen) antagonists. To investigate whether the phasic depolarization may influence the monosynaptic excitatory transmission to giant interneurons, the amplitude of the monosynaptic excitatory postsynaptic potential (EPSP) was compared between the onset of the ipsilateral locomotor burst and the burst mid‐point. The compound monosynaptic EPSP evoked from dorsal column was significantly smaller during the peak depolarization than at burst onset. The reduction of the amplitude of the EPSPs was not associated with any change of the membrane potential or input resistance of the giant interneurons, suggesting that this effect is mediated by a presynaptic mechanism. Phase‐dependent effects were also seen on burst and cycle duration following dorsal column stimulation. Thus, the locomotor‐related depolarizations in dorsal cell axons may represent a mechanism for a phasic gain control of sensory transmission during fictive locomotion.
Analysis of the Ion Channel Complement of the Rat Oligodendrocyte Progenitor in a Commonly Studied In vitro Preparation
Authors: Williamson A. V. , Compston D. A. S. , Randall A. D. 
Published: April 2006

AbstractWe have analysed the ion channel complement of the oligodendrocyte‐type 2 astrocyte (O‐2A) glial cell progenitor obtained from the commonly studied neonatal rat mixed brain preparation. Ionic currents, in O‐2A progenitors identified on both morphological and immunological grounds, were recorded using the whole‐cell variant of the patch‐clamp technique. The cells had an average resting membrane potential close to ‐50 mV and fired single action potentials in response to suprathreshold current injections. Using voltage‐clamp methods we were able to identify and characterize a voltage‐activated TTX‐sensitive Na+ current, two classes of voltage‐activated outward K+ currents, an inactivating inwardly rectifying K+ current, a voltage‐activated Cl‐ current and at least three classes of Ca2+ current.
Serpins Inhibit the Toxicity of Amyloid Peptides
Authors: Schubert David 
Published: April 2006

AbstractThe amyloid plaque in Alzheimer's disease (AD) contains numerous proteins, some of which may be relevant to the pathogenesis of the disease. The serine protease inhibitor α1‐antichymotrypsin is specifically localized in AD plaques. It is shown here that α1‐antichymotrypsin and several other serine protease inhibitors (serpins) inhibit the toxicity of amyloid peptides on primary cortical nerve cell cultures as well as a clonal cell line. This inhibition of toxicity is not mediated via the serpin enzyme complex receptor, the transferrin receptor, or by interference with the polymerization of amyloid fibrils. Since a variety of synthetic serine protease inhibitors mimic the effects of serpins on amyloid toxicity, it is likely that the antiprotease activities of serpins are responsible for their biological effects.
Evidence That Spinal Interneurons Undergo Programmed Cell Death Postnatally in the Rat
Authors: Lawson S. J. , Davies H. J. , Bennett J. P. , Lowrie M. B. 
Published: April 2006

AbstractProgrammed cell death has been demonstrated in several specific neuronal populations as a mechanism for modulating the population size following differentiation, but its applicability to all neuronal types is unclear. Evidence for programmed cell death in some populations such as the numerous spinal interneurons has been lacking. We have studied the incidence of apoptosis in the rat spinal cord with three different methods and found a previously undocumented wave of apoptosis occurring in spinal grey matter shortly after birth. The apoptotic morphology was confirmed ultrastructurally. Dying cells were identified as neurons by immunocytochemical labelling for neuronal markers and had an anatomical distribution which indicated that most of the apoptotic cells were interneurons not motoneurons. This wave of apoptosis has the characteristics of a discrete developmental process and occurs later than that of either ventral horn motoneurons or dorsal root ganglion cells, to which most spinal interneurons are connected. These findings indicate that interneurons do undergo programmed cell death, and we suggest that this occurs in response to the earlier reduction in size of their main synaptic targets.