bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pattern of ocular dominance columns in cat primary visual cortex: intra‐ and interindividual variability of column spacing and its dependence on genetic background
Authors: Kaschube Matthias , Wolf Fred , Puhlmann Mathias , Rathjen Stefan , Schmidt Karl‐Friedrich , Geisel Theo , Löwel Siegrid 
Published: December 2004

AbstractWe present a comprehensive analysis of the intrinsic variability of the periodicity of ocular dominance columns in cat primary visual cortex (area 17) and its relationship to genetic background and visual experience. We characterized the intra‐areal and interindividual variability of column spacing in a large set (n = 49) of ocular dominance patterns adapting a recently developed technique for the two‐dimensional analysis of orientation column patterns. Patterns were obtained from three different cat colonies (termed F, M and D), the cats having either normal visual experience or experimentally induced strabismus. Two‐dimensional maps of local column spacing were calculated for every pattern. In individual cortices, local column spacings varied by > 50% with the majority of column spacings ranging between 0.6 and 1.5 mm in different animals. In animals from colonies F and M (n = 29), the mean column spacing ranged between 1.03 and 1.27 mm and exhibited no significant differences, either between the two breeds or between strabismic and normal animals. The mean spacing was moderately clustered in the left and right brain hemisphere of individual animals but not in littermates. In animals from colony D (n = 2), average column spacing ranged between 0.73 and 0.95 mm, and was thus significantly different from the distribution of spacings in animals from breeds F and M, suggesting an influence of genetic factors on the layout of ocular dominance columns. Local column spacing exhibited a considerable systematic intra‐areal variation, with largest spacings along the representation of the horizontal meridian and smallest spacings along the peripheral representation of the vertical meridian. The total variability of ocular dominance column spacing comprised 24% systematic intra‐areal variation, 18% interindividual differences of mean column spacing and 58% nonsystematic intra‐areal variability.
MRI and in situ hybridization reveal early disturbances in brain size and gene expression in the megencephalic (mceph/mceph) mouse
Authors: Diez Margarita , Schweinhardt Petra , Petersson Susanna , Wang Fu‐Hua , Lavebratt Catharina , Schalling Martin , Hökfelt Tomas , Spenger Christian 
Published: December 2004

AbstractThe mouse model for megencephaly, mceph/mceph, carries a truncating deletion in the Shaker‐related voltage gated potassium channel gene 1. Affected mice display neurological disturbances and motor dysfunctions. Symptoms begin to show at 3–4 weeks of age. The cause of the brain enlargement is not clear. To elucidate early events in the development of the disease we used magnetic resonance imaging (MRI) to quantify, over time, the increase in size of several discrete brain regions in the same mice at 3, 8 and 12 weeks of age. We also analysed markers for neuropeptides and growth factors to explore their possible involvement at an early stage. The results show an enlargement of the total coronal area of the brain already at 3 weeks of age. Total brain volume, ventral cortex, hippocampal formation and cerebral cortex were enlarged at 8 weeks and onwards. Thalamus, brainstem, cerebellum and spinal cord did not differ from controls even at 12 weeks. We also report distinct disturbances in the expression of brain‐derived neurotrophic factor, insulin‐like growth factor binding protein 6 and several neuropeptides at 2 and 3 weeks of age, that is, before an obvious behavioural phenotype can be observed. These results provide an objective description of the size changes in different brain regions of the mceph/mceph mouse, and suggest that certain molecules could be involved in the early processes underlying these changes.
Active release of glycine or d‐serine saturates the glycine site of NMDA receptors at the cerebellar mossy fibre to granule cell synapse
Authors: Billups Daniela , Attwell David 
Published: December 2004

AbstractThe current and calcium influx generated by NMDA receptors depend on the concentration of the coagonist glycine, or its analogue d‐serine, in the synaptic cleft. If there is no release of glycine, the ionic stoichiometry of the glial GlyT1 glycine transporters expressed near NMDA receptors in the brain should be able to lower the extracellular glycine concentration to below the EC50 for coactivation of NMDA receptors. We examined whether changing the glycine or d‐serine concentration in the superfusion solution altered the NMDA receptor mediated component of the synaptic current at the rat cerebellar mossy fibre to granule cell synapse. Adding up to 100 µm glycine or d‐serine had no effect, implying that the glycine site is saturated. Using the competitive glycine site antagonist 7‐chlorokynurenate, and plausible values for the kinetic parameters of NMDA receptors, we estimate that during activation of the mossy fibres the concentration of glycine or d‐serine in the synaptic cleft is at least 4.6 µm or 1.5 µm, respectively, requiring active release of glycine or d‐serine.
LRRN6A/LERN1 (leucine‐rich repeat neuronal protein 1), a novel gene with enriched expression in limbic system and neocortex
Authors: Carim‐Todd Laura , Escarceller Mònica , Estivill Xavier , Sumoy Lauro 
Published: December 2004

AbstractHuman chromosome 15q24‐q26 is a very complex genomic region containing several blocks of segmental duplications to which susceptibility to anxiety disorders has been mapped (Gratacos et al., 2001, Cell, 106, 367–379; Pujana et al., 2001, Genome Res., 11, 98–111). Through an in silico gene content analysis of the 15q24‐q26 region we have identifie1d a novel gene, LRRN6A (leucine‐rich repeat neuronal 6A), and confirmed its location to the centromeric end of this complex region. LRRN6A encodes a transmembrane leucine‐rich repeat protein, LERN1 (leucine‐rich repeat neuronal protein 1), with similarity to proteins involved in axonal guidance and migration, nervous system development and regeneration processes. The identification of homologous genes to LRRN6A on chromosomes 9 and 19 and the orthologous genes in the mouse genome and other organisms suggests that LERN proteins constitute a novel subfamily of LRR (leucine‐rich repeat)‐containing proteins. The LRRN6A expression pattern is specific to the central nervous system, highly and broadly expressed during early stages of development and gradually restricted to forebrain structures as development proceeds. Expression level in adulthood is lower in general but remains stable and significantly enriched in the limbic system and cerebral cortex. Taken together, the confirmation of LRRN6A's expression profile, its predicted protein structure and its similarity to nervous system‐expressed LRR proteins with essential roles in nervous system development and maintenance suggest that LRRN6A is a novel gene of relevance in the molecular and cellular neurobiology of vertebrates.
The physiological and morphological characteristics of interneurons caudal to the trigeminal motor nucleus in rats
Authors: Min Ming‐Yuan , Hsu Pei‐Chien , Yang Hsiu‐Wen 
Published: December 2004

AbstractIn this study we have characterized the membrane properties and morphology of interneurons which lie between the caudal pole of the trigeminal motor nucleus and the rostral border of the facial motor nucleus. Previous studies suggest that many of these interneurons may participate in the genesis of rhythmical jaw movements. Saggital brainstem slices were taken from rats aged 5–8 days. Interneurons lying caudal to the trigeminal motor nucleus were visualized using near‐infrared differential interference contrast (DIC) microscopy, and were recorded from using patch pipettes filled with a K‐gluconate‐ and biocytin‐based solution. The 127 neurons recorded could be categorized into three subtypes on the basis of their responses to injection of depolarizing current pulses, namely tonic firing (type I), burst firing (type II) and spike‐adaptive (type III) neurons. Type I interneurons had a higher input resistance and a lower rheobase than type II neurons. All three neuron subtypes showed ‘sag’ of the voltage response to injection of large‐amplitude hyperpolarizing current pulses, and, in addition, also showed rectification of the voltage response to injection of depolarizing current pulses, with type II neurons showing significantly greater rectification than type I neurons. The axonal arborizations were reconstructed for 44 of 63 neurons labelled with tracer. Neurons of each subtype were found to issue axon collaterals terminating in the brainstem nuclei, including the parvocellular reticular nucleus (PCRt), the trigeminal motor nucleus (Vmot), the supratrigeminal nucleus or the trigeminal mesencephalic nucleus. Twenty‐five of the 43 neurons issued collaterals which terminated in the Vmot and the other brainstem nuclei. When viewed under 100× magnification, the collaterals of some interneurons were seen to give off varicosities and end‐terminations which passed close to the somata of unidentified neurons in the trigeminal motor nucleus and in the area close to the interneuron soma itself. This suggests that the interneurons may make synaptic contacts both on motoneurons and also on nearby interneurons. These results provide data on the membrane properties of trigeminal interneurons and evidence for their synaptic connections both with nearby interneurons and also with motoneurons. Thus, the interneurons examined could play roles in the shaping, and possibly also in the generation, of rhythmical signals to trigeminal motoneurons.
Contribution of spinal inhibitory receptors in heterosegmental antinociception induced by noxious stimulation
Authors: Tambeli C. H. , Quang P. , Levine J. D. , Gear R. W. 
Published: December 2004

AbstractNoxious (i.e. painful) stimulation in the rat induces profound heterosegmental antinociception as demonstrated by the ability of either thermal stimulation (50 °C water) or subdermal capsaicin injection in the hindpaw to attenuate the nociceptive trigeminal jaw‐opening reflex. Importantly, noxious stimulus‐induced antinociception (NSIA) is mediated by endogenous opioids (as well as other neurotransmitters) in nucleus accumbens, as indicated by the ability of intra‐accumbens administration of mu‐ or delta‐opioid receptor antagonists to block NSIA. Although noxious peripheral stimulation is known to release excitatory neurotransmitters such as glutamate at the level of the spinal cord, the present study was designed to test the hypothesis that NSIA depends on further activation of spinal inhibitory receptors. This hypothesis was based on findings that inhibition of spinal processing (e.g. intrathecal local anaesthetic administration) also produces heterosegmental antinociception mediated by endogenous opioids in nucleus accumbens. Thus, to reconcile the paradoxical findings that both spinal excitation and inhibition appear to activate the same nucleus accumbens opioid‐mediated antinociceptive mechanism, we investigated whether spinal administration of antagonists for inhibitory receptors would block the antinociceptive effect of subdermal capsaicin. We report that spinal administration of selective antagonists for mu‐opioid (Cys2, Tyr3, Orn5, Pen7amide), kappa‐opioid (nor‐binaltorphimine), GABA‐A (bicuculline), GABA‐B (CGP 35348) and glycine (strychnine) receptors significantly reduced NSIA. The selective delta‐opioid receptor antagonist naltrindole had no significant effect. These results, together with our previous findings, suggest that peripheral noxious stimuli release endogenous opioids, GABA and glycine in the spinal cord which, in turn, inhibit tonic pronociceptive spinal activity to produce heterosegmental antinociception mediated in nucleus accumbens.
A reporter allele for investigating connexin 26 gene expression in the mouse brain
Authors: Filippov Mikhail A. , Hormuzdi Sheriar G. , Fuchs Elke C. , Monyer Hannah 
Published: December 2004

AbstractA variety of connexins are expressed in the diverse cell types of the central nervous system and are thought to regulate some of the functional properties exhibited by immature and mature cells. A proper understanding of the role of specific connexins in these processes requires an unambiguous characterization of their spatial and temporal pattern of expression. In order to define the cellular distribution of connexin 26 (Cx26) in the mouse we have generated a reporter allele (Cx26lacZ) by genetically manipulating the locus so that the β‐galactosidase (lacZ) gene is expressed from the endogenous Cx26 promoter. This modification decreased expression from the allele and resulted in embryonic lethality for the Cx26lacZ/lacZ genotype in accordance with previous studies on Cx26 knock‐out animals indicating that Cx26‐containing gap junctions are necessary for embryonic development. Despite the lower than expected transcript levels, the amount of lacZ protein produced in heterozygous mice was sufficient to label tissues known to contain Cx26, such as liver, kidney, skin, cochlea, small intestine, placenta and thyroid gland. In the embryonic and mature central nervous system, however, lacZ was restricted to meningeal cells and could not be detected in either neurons or glia. The absence of Cx26 mRNA in these cells could also be confirmed by reverse transcription–polymerase chain reaction and in situ hybridization. Our experiments indicate that the Cx26lacZ mouse line can be used as a reporter of Cx26 gene expression and suggest that Cx26, contrary to previous reports, is restricted to the meninges in both embryonic and adult brain.
Ca2+‐independent muscarinic excitation of rat medial entorhinal cortex layer V neurons
Authors: Egorov Alexei V. , Angelova Plamena R. , Heinemann Uwe , Müller Wolfgang 
Published: December 2004

AbstractCholinergic activation of entorhinal cortex (EC) layer V neurons plays a crucial role in the medial temporal lobe memory system and in the pathophysiology of temporal lobe epilepsy. Here, we demonstrate that muscarinic activation by focal application of carbachol depolarizes EC layer V neurons and induces epileptiform activity in rat brain slices. These seizure‐like bursts are associated with a somatic [Ca2+]i increase of 293 ± 82 nm and are blocked by the glutamate receptor antagonists CNQX and APV. Muscarinic activation did not directly evoke a [Ca2+]i increase, but subthreshold and suprathreshold depolarization did. Functional axon mapping revealed local axon branching as well as axon collaterals ascending to layers II and III. During blockade of ionotropic glutamatergic AMPA and NMDA receptors, carbachol depolarized layer V neurons by +7.5 ± 3.4 mV. This direct muscarinic depolarization was associated with a conductance increase of 35 ± 10.3% (+4.3 ± 1.25 nS). Intracellular buffering of [Ca2+]i changes did not block this depolarization, but prolonged action potential duration and reduced adaptation of action potential firing. The muscarinic depolarization was neither blocked by combining intracellular Ca2+‐buffering (EGTA or BAPTA) with non‐specific Ca2+‐channel inhibition by Ni+ (1 mm), nor by Ba2+ (1 mm) nor during inhibition of the h‐current by 2 mm Cs+. In whole‐cell patch‐clamp recording, reversal of the muscarinic current occurred at about −45 mV and −5 mV with complete substitution of intrapipette K+ with Cs+. Thus, muscarinic depolarization of EC layer V neurons appears to be primarily mediated by Ca2+‐independent activation of non‐specific cation channels that conduct K+ about three times as well as Na+.
5‐HT inhibits N‐type but not L‐type Ca2+ channels via 5‐HT1A receptors in lamprey spinal neurons
Authors: Hill Russell H. , Svensson Erik , Dewael Yannick , Grillner Sten 
Published: December 2004

Abstract5‐HT is a potent modulator of locomotor activity in vertebrates. In the lamprey, 5‐HT dramatically slows fictive swimming. At the neuronal level it reduces the postspike slow afterhyperpolarization (sAHP), which is due to apamin‐sensitive Ca2+‐dependent K+ channels (KCa). Indirect evidence in early experiments suggested that the sAHP reduction results from a direct action of 5‐HT on KCa channels rather than an effect on the Ca2+ entry during the action potential [Wallén et al., (1989) J. Neurophysiol., 61, 759–768]. In view of the characterization of different subtypes of Ca2+ channels with very different properties, we now reinvestigate if there is a selective action of 5‐HT on a Ca2+ channel subtype in dissociated spinal neurons in culture. 5‐HT reduced Ca2+ currents from high voltage activated channels. N‐type, but not L‐type, Ca2+ channel blockers abolished this 5‐HT‐induced reduction. It was also confirmed that 5‐HT depresses Ca2+ currents in neurons, including motoneurons, in the intact spinal cord. 8‐OH‐DPAT, a 5‐HT1A receptor agonist, also inhibited Ca2+ currents in dissociated neurons. After incubation in pertussis toxin, to block Gi/o proteins, 5‐HT did not reduce Ca2+ currents, further indicating that the effect is caused by an activation of 5‐HT1A receptors. As N‐type, but not L‐type, Ca2+ channels are known to mediate the activation of KCa channels and presynaptic transmitter release at lamprey synapses, the effects of 5‐HT reported here can contribute to a reduction in both actions.
Numb rats walk – a behavioural and fMRI comparison of mild and moderate spinal cord injury
Authors: Hofstetter Christoph P. , Schweinhardt Petra , Klason Tomas , Olson Lars , Spenger Christian 
Published: December 2004

AbstractAssessment of sensory function serves as a sensitive measure for predicting the functional outcome following spinal cord injury in patients. However, little is known about loss and recovery of sensory function in rodent spinal cord injury models as most tests of sensory functions rely on behaviour and thus motor function. We used functional magnetic resonance imaging (fMRI) to investigate cortical and thalamic BOLD‐signal changes in response to limb stimulation following mild or moderate thoracic spinal cord weight drop injury in Sprague–Dawley rats. While there was recovery of close to normal hindlimb motor function as determined by open field locomotor testing following both degrees of injury, recovery of hindlimb sensory function as determined by fMRI and hotplate testing was only seen following mild injury and not following moderate injury. Thus, moderate injury can lead to near normal hindlimb motor function in animals with major sensory deficits. Recovered fMRI signals following mild injury had a partly altered cortical distribution engaging also ipsilateral somatosensory cortex and the cingulate gyrus. Importantly, thoracic spinal cord injury also affected sensory representation of the upper nonaffected limbs. Thus, cortical and thalamic activation in response to forelimb stimulation was significantly increased 16 weeks after spinal cord injury compared to control animals. We conclude that both forelimb and hindlimb cortical sensory representation is altered following thoracic spinal cord injury. Furthermore tests of sensory function that are independent of motor behaviour are needed in rodent spinal cord injury research.
Internalization at glutamatergic synapses during development
Authors: Petralia Ronald S. , Wang Ya‐Xian , Wenthold Robert J. 
Published: December 2004

AbstractGlutamate receptors are internalized from the cell membrane via clathrin‐coated pits. However, little is known about where this occurs − whether at or near the synapse or at some distance from it. In this study we used immunogold localization in the rat brain (mainly hippocampus) to show that clathrin‐coated pits are found both at the edge of the synaptic active zone and at further postsynaptic distances, including on the sides of the spine; we also localize these pits specifically to glutamatergic synapses. In addition, we show that clathrin‐coated pits can internalize both N‐methyl‐d‐aspartate (in vivo) and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (in vitro data only) receptors at extrasynaptic sites not associated directly with synapses. Also, caveolin might be prevalent at excitatory synapses, although it is not known whether it is involved in receptor internalization, receptor stabilization, or some other function.
Herpes simplex virus type 1 inoculation enhances hippocampal excitability and seizure susceptibility in mice
Authors: Wu Hung‐Ming , Huang Chiung‐Chun , Chen Shun‐Hua , Liang Ying‐Ching , Tsai Jing‐Jane , Hsieh Ching‐Liang , Hsu Kuei‐Sen 
Published: December 2004

AbstractHerpes simplex virus type 1 (HSV‐1) is the major pathogen related to epilepsy. However, little is known about the pathogenesis of HSV‐1‐associated epilepsy. Here, we report that corneal inoculation of mice with HSV‐1 induces acute spontaneous behavioural and electrophysiological seizures and chronically increases hippocampal excitability and seizure susceptibility. In slices from infected mice, the surviving hippocampal CA3 pyramidal neurons exhibited a more depolarizing resting membrane potential concomitant with an increase in membrane input resistance. They also had a lower threshold for generating synchronized bursts and a decrease in the amplitude of afterhyperpolarization (AHP) than did controls. These results suggest that a direct change in the excitability of the hippocampal CA3 neuronal network could play an important role in facilitating the development of acute seizures and subsequent epilepsy.
Control of eye orientation: where does the brain's role end and the muscle's begin?
Authors: Angelaki Dora E. , Hess Bernhard J. M. 
Published: December 2004

AbstractOur understanding of how the brain controls eye movements has benefited enormously from the comparison of neuronal activity with eye movements and the quantification of these relationships with mathematical models. Although these early studies focused on horizontal and vertical eye movements, recent behavioural and modelling studies have illustrated the importance, but also the complexity, of extending previous conclusions to the problems of controlling eye and head orientation in three dimensions (3‐D). An important facet in understanding 3‐D eye orientation and movement has been the discovery of mobile, soft‐tissue sheaths or ‘pulleys’ in the orbit which might influence the pulling direction of extraocular muscles. Appropriately placed pulleys could generate the eye‐position‐dependent tilt of the ocular rotation axes which are characteristic for eye movements which follow Listing's law. Based on such pulley models of the oculomotor plant it has recently been proposed that a simple two‐dimensional (2‐D) neural controller would be sufficient to generate correct 3‐D eye orientation and movement. In contrast to this apparent simplification in oculomotor control, multiple behavioural observations suggest that the visuo‐motor transformations, as well as the premotor circuitry for saccades, pursuit eye movements and the vestibulo‐ocular reflexes, must include a neural controller which operates in 3‐D, even when considering an eye plant with pulleys. This review summarizes the most recent work and ideas on this controversy. In addition, by proposing directly testable hypotheses, we point out that, in analogy to the previously successful steps towards elucidating the neural control of horizontal eye movements, we need a quantitative characterization first of motoneuron and next of premotor neuron properties in 3‐D before we can succeed in gaining further insight into the neural control of 3‐D motor behaviours.