bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cloning and characterization of SDF‐1γ, a novel SDF‐1 chemokine transcript with developmentally regulated expression in the nervous system
Authors: Gleichmann Marc , Gillen Clemens , Czardybon Margarete , Bosse Frank , Greiner‐Petter Regine , Auer Johannes , Müller Hans Werner 
Published: March 2003

AbstractThe cytokines SDF‐1α and ‐1β are two alternatively spliced variants of the CXC (α) chemokines that are highly conserved among species. SDF‐1α was shown to function as a B‐cell maturation factor, a ligand for the CXCR4 (LESTR/fusin) chemokine receptor, thereby inhibiting replication of T cell‐tropic HIV‐1 strains and inducing cell death in human neuronal cell lines. In this report the cloning of the rat SDF‐1β cDNA and a new SDF‐1 isoform, SDF‐1γ, are presented. Using Northern blot analysis, the expression pattern of both isoforms was studied in different tissues and it is shown that during postnatal development of the central and peripheral nervous system SDF‐1β‐ and SDF‐1γ‐mRNA expression is inversely regulated. Whilst SDF‐1β‐mRNA is the predominant isoform in embryonic and early postnatal nerve tissue, SDF‐1γ‐mRNA is expressed at higher levels in adulthood. After peripheral nerve lesion a transient increase in SDF‐1β‐mRNA expression is observed. As revealed by in situ hybridization, neurons and Schwann cells are the main cellular sources of both SDF‐1β and SDF‐1γ mRNAs in the nervous system. Computer‐assisted analysis revealed that both transcripts encode secreted peptides with putative proteolytic cleavage sites which might generate novel neuropeptides.
Neurotrophin 3 potentiates glutamatergic responses of IHC afferents in the cochlea in vivo
Authors: Oestreicher E. , Knipper M. , Arnold A. , Zenner H. P. , Felix D. 
Published: March 2003

AbstractNeurotrophins have traditionally been regarded as slow‐acting signals essential for neuronal survival and differentiation. Recent studies with neuronal slices, cultures and nerve ending preparations have shown that neurotrophins generate acute changes in nerve activity. Among the secondary sensory cells are the inner hair cells (IHC) and taste buds, cells which express the neurotrophic factors necessary for the survival of their innervating neurons. If in these cells neurotrophins acutely affect the nerve activity of their afferent neurons, as in the central nervous system (CNS), this may have important functional implications for the corresponding sensory transduction processes. The neurotrophin NT‐3 has been reported to be expressed in IHCs. We chose an in vivo application system for the microiontophoretic supply of NT‐3 in the subsynaptic region of the IHC. The effect of NT‐3 on spontaneous and evoked afferent cochlear nerve activities in adult guinea pig inner ear was studied. We observed that NT‐3 rapidly increases the spontaneous and glutamate‐evoked firing rate of IHC afferents. Moreover, firing induced by both N‐methyl‐ d‐aspartate (NMDA) and α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) were specifically enhanced during the presence of NT‐3, a process which was selectively blocked by the tyrosine kinase receptor inhibitor K252a. Because we localized NT‐3 mRNA not only in IHCs but also in the spiral ganglion, we propose that similar to other sensory systems, afferent and autocrine neurotrophin activities may be responsible for survival of cochlear neurons. In addition, NT‐3 in IHCs may operate as a signal‐dependent, intrinsic neuromodulator and/or neuroprotector.
Characterization of calcium currents in functionally mature mouse spinal motoneurons
Authors: Carlin K. P. , Jiang Z. , Brownstone R. M. 
Published: March 2003

AbstractMotoneurons integrate synaptic input and produce output in the form of trains of action potentials such that appropriate muscle contraction occurs. Motoneuronal calcium currents play an important role in the production of this repetitive firing. Because these currents change in the postnatal period, it is necessary to study them in animals in which the motor system is ‘functionally mature’, that is, animals that are able to weight‐bear and walk. In this study, calcium currents were recorded using whole‐cell patch‐clamp techniques from large (> 20 μm) ventral horn cells in lumbar spinal cord slices prepared from mature mice. Ninety percent (nine out of 10) of the recorded cells processed for choline acetyltransferase were found to be cholinergic, confirming their identity as motoneurons. A small number of motoneurons were found to have currents with low‐voltage‐activated (T‐type) characteristics. Pharmacological dissection of the high‐voltage‐activated current demonstrated ω‐agatoxin‐TK‐ (P/Q‐type), ω‐conotoxin GVIA‐ (N‐type), and dihydropyridine‐ and FPL‐64176‐sensitive (L‐type) components. A cadmium‐sensitive component of the current that was insensitive to these chemicals (R‐type) was also seen in these cells. These results indicate that the calcium current in lumbar spinal motoneurons from functionally mature mice is mediated by a number of different channel subtypes. The characterization of these calcium channels in mature mammalian motoneurons will allow for the future study of their modulation and their roles during behaviours such as locomotion.
Distinct expression patterns of Eph receptors and ephrins relate to the structural organization of the adult rat peripheral vestibular system
Authors: Matsunaga Tatsuo , Greene Mark I. , Davis James G. 
Published: March 2003

AbstractEph receptors and their ligands, termed ephrins, have been implicated in axon guidance, neuron–target interactions, regional compartmentalization, and synaptic functions in nervous systems. These activities of the Eph family molecules prompted us to investigate whether these molecules play roles in the maintenance, regeneration and plasticity in the mature peripheral vestibular system. Using reverse transcription‐polymerase chain reaction (RT‐PCR), Western blot and immunocytochemical analyses, we identified distinct and reciprocal expression patterns of full‐length isoforms of EphA5, EphA6, EphA7, EphB1, ephrin‐A2 and ephrin‐B1 that correlated with structural features of the peripheral vestibular system in adult rats. All of the Eph receptors and ephrins examined were localized in the cell bodies of vestibular ganglion neurons in vivo and in vitro, and were readily detected in their outgrowing neurites in vitro. In the utricle, these molecules were localized in distinct cellular and subcellular compartments corresponding to discrete features of utricular afferent innervation, e.g. defasciculation, branching and synapse formation. Taken together, these results identify the Eph receptors and ephrins as candidate molecular substrates for defining some aspects of the structural organization of the adult peripheral vestibular system.
The distribution and origin of the calretinin‐containing innervation of the nucleus accumbens of the rat
Authors: Bubser Michael , Scruggs Jennifer L. , Young Cheryl D. , Deutch Ariel Y. 
Published: March 2003

AbstractThe nucleus accumbens of the rat consists of several subregions that can be distinguished on the basis of histochemical markers. For example, the calcium‐binding protein calbindin D28k is a useful marker of the core compartment of the nucleus accumbens. Calretinin, another calcium‐binding protein, is found in a dense fibre plexus in the accumbal shell and septal pole regions. The source of the accumbal calretinin innervation is not known. We examined the distribution of calretinin in the nucleus accumbens and used tract‐tracing and lesion methods to determine the source of this calretinin innervation. Intense calretinin immunoreactivity was present in the medial shell, but the density of calretinin axons diminished sharply in the ventrolateral shell. Regions of dense calretinin immunostaining and those areas with calbindin‐like immunoreactive cell bodies were generally segregated in the nucleus accumbens, although some overlap in the transition region between the core and shell was seen. Small clusters of calretinin‐immunoreactive fibres were seen in the core, where they were restricted to calbindin‐negative patches. Injections of the anterograde tracer biotinylated dextran amine into the paraventricular thalamic nucleus labelled fibres in calretinin‐rich regions of the accumbens. Conversely, injections of Fluoro‐gold into the accumbal shell retrogradely labelled numerous cells in the paraventricular thalamic nucleus that were calretinin‐immunoreactive. Electrolytic lesions of the paraventricular thalamic nucleus reduced calretinin levels in the shell by ≈ 80%. These data indicate that the calretinin innervation of the nucleus accumbens is derived primarily from the thalamic paraventricular nucleus, and marks accumbal territories that are largely complementary to those defined by calbindin.
Progesterone regulation of GABAA receptor plasticity in adult rat supraoptic nucleus
Authors: Fénelon Valérie S. , Herbison Allan E. 
Published: March 2003

AbstractMarked plasticity in GABAA receptor signalling occurs in adult oxytocin neurons of the supraoptic nucleus (SON) through the modulation of GABAA receptor α subunits during pregnancy. The present studies were undertaken to examine the potential mechanisms underlying this plasticity. In vivo microdialysis experiments in conscious rats revealed that no significant changes in extracellular GABA concentrations occurred within the SON over the last two days of pregnancy and the time of parturition itself. In situ hybridization studies examined the effects of gonadal steroid manipulation upon the GABAA receptor subunits expressed by SON neurons (α1, α2, β2 and γ2 subunits) and demonstrated that cellular levels of the α1 subunit were increased following 8 days oestrogen and progesterone treatment. Estrogen alone or allopregnanolone, the progesterone derivative, had no effect on α1 subunit mRNA expression in the SON. Immunocytochemical experiments demonstrated progesterone receptors in many neural populations but not within the SON of late pregnant rats. These studies indicate that alterations in endogenous GABA release within the SON are unlikely to be responsible for the GABAA receptor plasticity exhibited by oxytocin neurons in late pregnancy. Rather, data demonstrate that the fluctuating concentrations of progesterone during pregnancy act indirectly on SON neurons to modulate α1 subunit mRNA expression. Together, these experiments provide evidence for the ligand‐independent induction of GABAA receptor plasticity in the adult brain by progesterone.
Coding for auditory space in the superior colliculus of the rat
Authors: Gaese B. H. , Johnen A. 
Published: March 2003

AbstractAlthough the rat is often used to determine behavioural sound‐localization capabilities or neuronal computation of binaural information, the representation of auditory space in the rat brain has not been investigated so far. We obtained extracellular recordings from auditory neurons in the superior colliculus of anaesthetized rats and examined them for spatial tuning characteristics and topographical order. Many neurons (73%) showed significant tuning, with a single peak in the azimuth response profiles based on spike rates and response latencies. Best azimuth values from neurons in one SC were generally tuned to contralateral and rarely to frontal or ipsilateral directions. Tuning width was mostly broad; at supra‐threshold sound pressure levels (35 dB SPL), 55% of the units had a tuning width of > 120° in contralateral space. Additionally, tuning width increased with stimulation intensity. A significant but considerably scattered topographical order of best azimuth directions was observed in the deep layers of the superior colliculus with frontal directions being represented closer to the rostral pole. Tuned auditory units in the intermediate layers of the superior colliculus, however, showed no systematic spatial arrangement. This pattern was confirmed by analysing best azimuth directions from simultaneously recorded units. Our results indicate that the rat superior colliculus contains a representation of auditory space which is similar to that described for other small mammals.
Dendritic L‐type calcium currents in mouse spinal motoneurons: implications for bistability
Authors: Carlin K. P. , Jones K. E. , Jiang Z. , Jordan L. M. , Brownstone R. M. 
Published: March 2003

AbstractThe intrinsic properties of mammalian spinal motoneurons provide them with the capability to produce high rates of sustained firing in response to transient inputs (bistability). Even though it has been suggested that a persistent dendritic calcium current is responsible for the depolarizing drive underlying this firing property, such a current has not been demonstrated in these cells. In this study, calcium currents are recorded from functionally mature mouse spinal motoneurons using somatic whole‐cell patch‐clamp techniques. Under these conditions a component of the current demonstrated kinetics consistent with a current originating at a site spatially segregated from the soma. In response to step commands this component was seen as a late‐onset, low amplitude persistent current whilst in response to depolarizing–repolarizing ramp commands a low voltage clockwise current hysteresis was recorded. Simulations using a neuromorphic motoneuron model could reproduce these currents only if a noninactivating calcium conductance was placed in the dendritic compartments. Pharmacological studies demonstrated that both the late‐onset and hysteretic currents demonstrated sensitivity to both dihydropyridines and the L‐channel activator FPL‐64176. Furthermore, the α1D subunits of L‐type calcium channels were immunohistochemically demonstrated on motoneuronal dendrites. It is concluded that there are dendritically located L‐type channels in mammalian motoneurons capable of mediating a persistent depolarizing drive to the soma and which probably mediate the bistable behaviour of these cells.
Nitric oxide released by gastric mechanoreceptors modulates nicotinic activation of coeliac plexus neurons in the rabbit
Authors: Quinson N. , Niel J. P. , Miolan J. P. 
Published: March 2003

AbstractThe effects on the nicotinic activation of the coeliac plexus neurons of nitric oxide (NO) released within the coeliac plexus by gastric mechanoreceptors, in particular during gastroduodenal inhibitory reflex, were assessed. This study was performed in the rabbit on an in vitro preparation of the coeliac plexus connected to the stomach and the duodenum. The electrical activity of ganglionic neurons was recorded with intracellular recording techniques. Water‐filled balloons were used for gastric distensions and recording of duodenal motility. When a 10‐s train of pulses (20–40Hz) of supramaximal intensity was applied to the splanchnic nerves, gradual depression of nicotinic activation occurred. Gastric distension (50 mL, 7.5 min) modulated this depression phenomenon by inhibiting or facilitating the nicotinic activation. In the neurons impaled during the recording of duodenal motility, gastric distension triggered an inhibition of nicotinic activation concomitantly with a gastroduodenal inhibitory reflex organized by the coeliac plexus. If the gastric distensions were performed while the coeliac plexus was superfused by a NO scavenger, the nicotinic activation was unaffected and the gastroduodenal inhibitory reflex was abolished. Moreover, when the coeliac plexus was superfused with an inhibitor of nitric oxide synthase, gastric distensions were without effect on the nicotinic activation. These results demonstrate that NO released within the coeliac plexus by gastric mechanoreceptors, in particular during the gastroduodenal inhibitory reflex, modulates the central nicotinic activation of coeliac plexus neurons, so NO released within a prevertebral ganglion by gastric afferent fibres, in particular during the organization by this ganglion of a reflex regulating the gastrointestinal tract motility, also exerts a gating of the central inputs to the ganglionic neurons.
Cross‐modal plasticity of the corticothalamic circuits in rats enucleated on the first postnatal day
Authors: Négyessy László , Gál Viktor , Farkas Tamás , Toldi József 
Published: March 2003

AbstractReorganization of the reciprocal corticothalamic connections was studied as a possible anatomical substrate of the cross‐modal compensation of the missing visual input of the visual cortex by somatosensory‐evoked activities in neonatally enucleated rats. The use of quantitative retrograde tract‐tracing techniques revealed that the contribution of the lateral posterior thalamic nucleus (LP) is significantly increased following enucleation, while that of the dorsolateral geniculate and the lateral dorsal nuclei is decreased in the thalamocortical afferentation of a region in visual cortical area 17. In contrast with the control rats, a dense terminal arborization of afferents was labelled in the LP after the injection of anterograde tracer into the barrel cortex of the enucleated rats. The injection of anterograde tracer into the visual cortex also demonstrated a massive afferentation into the LP of the enucleated rats. Visual and somatosensory corticothalamic afferents exhibited similar ultrastructural features in the LP after enucleation, but their synaptic organizations differed as regards the diameter of the postsynaptic dendrites. Taken together with the previous observations, these results suggest a central role for the LP in the transmission of the somatosensory‐evoked activities to the visual cortex after early blindness.
Seizures induce widespread upregulation of cystatin B, the gene mutated in progressive myoclonus epilepsy, in rat forebrain neurons
Authors: D'amato Elena , Kokaia Zaal , Nanobashvili Avtandil , Reeben Mati , Lehesjoki Anna‐Elina , Saarma Mart , Lindvall Olle 
Published: March 2003

AbstractLoss of function mutations in the gene encoding the cysteine protease inhibitor, cystatin B (CSTB), are responsible for the primary defect in human progressive myoclonus epilepsy (EPM1). CSTB inhibits the cathepsins B, H, L and S by tight reversible binding, but little is known regarding its localization and physiological function in the brain and the relation between the depletion of the CSTB protein and the clinical symptoms in EPM1. We have analysed the expression of mRNA and protein for CSTB in the adult rat brain using in situ hybridization and immunocytochemistry. In the control brains, the CSTB gene was differentially expressed with the highest levels in the hippocampal formation and reticular thalamic nucleus, and moderate levels in amygdala, thalamus, hypothalamus and cortical areas. Detectable levels of CSTB were found in virtually all forebrain neurons but not in glial cells. Following 40 rapidly recurring seizures evoked by hippocampal kindling stimulations, CSTB mRNA expression showed marked bilateral increases in the dentate granule cell layer, CA1 and CA4 pyramidal layers, amygdala, and piriform and parietal cortices. Maximum levels were detected at 6 or 24 h, and expression had reached control values at 1 week post‐seizures. The changes of mRNA expression were accompanied by transient elevations (at 6–24 h) of CSTB protein in the same brain areas. These findings demonstrate that seizure activity leads to rapid and widespread increases of the synthesis of CSTB in forebrain neurons. We propose that the upregulation of CSTB following seizures may counteract apoptosis by binding cysteine proteases.
Expression of novel antioxidant thioredoxin‐2 in the rat brain
Authors: Rybnikova Elena , Damdimopoulos Anastasios E. , Gustafsson Jan‐Åke , Spyrou Giannis , Pelto‐Huikko Markku 
Published: March 2003

AbstractThioredoxins are a class of small redox‐regulating proteins that have been implicated in the control of various aspects of cellular functions and seem to be one of the key regulators of signalling in the cellular responses to various stresses. Thioredoxin‐2 (Trx2) is a novel mammalian thioredoxin which, in contrast to previously known cytosolic thioredoxin (Trx1), has been localized to the mitochondria. Trx2 is abundantly expressed in skeletal muscle, heart and adrenal gland, as well as in some other peripheral tissues with high metabolic activity. Using in situ hybridization and immunohistochemistry, we have studied the distribution and regulation of Trx2 expression in the rat brain. Trx2 mRNA and protein are highly expressed in the neurons in several brain regions, including the olfactory bulb, frontal cortex, hippocampus, some hypothalamic and thalamic nuclei, cerebellum and numerous brainstem nuclei. In addition, the Trx2 mRNA expression in paraventricular hypothalamic nucleus and reticular thalamic nucleus was found to be sensitive to peripheral glucocorticoids, as dexamethasone treatment caused significant elevation of Trx2 mRNA level in this area. No changes in other brain areas were observed after dexamethasone treatment. These findings implicate a significant regulatory and/or protective function of Trx2 in the nervous system.
Participation of low‐threshold calcium spikes in excitatory synaptic transmission in guinea pig medial frontal cortex
Authors: De La Peña Elvira , Geijo‐Barrientos Emilio 
Published: March 2003

AbstractWe studied the activation of low‐threshold calcium spikes (LTS) by excitatory postsynaptic potentials in pyramidal neurons from guinea pig medial frontal cortex with intracellular recording. We used extracellular bicuculline and phaclofen and intracellular QX‐314 to block inhibitory synaptic potentials and sodium currents. Postsynaptic potentials were evoked by stimulation of layer I. We found that large (> 10–15 mV) excitatory synaptic potentials evoked from membrane potentials more negative than −75 mV were able to trigger LTS. The activation of LTS resulted in an increase of the rising slope or amplitude of the synaptic potentials depending on the size of the excitatory postsynaptic potential (EPSP). We used 100 μm NiCl2 to confirm the presence of LTS as part of the EPSPs. The N‐methyl‐d‐aspartate (NMDA) and non‐NMDA components of the excitatory synaptic potentials were isolated using (±)2‐amino‐5‐phosphonovaleric acid (APV; 50 μm) or 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX; 20 μm); both components could, independently, trigger an LTS. With recordings made with K+ acetate‐filled electrodes, we show that the activation of LTS was critical to allow excitatory synaptic potentials to reach the threshold of action potential firing; also, this amplification of synaptic responses produced the firing of more than a single action potential by the postsynaptic cell. These results demonstrate that in cortical pyramidal neurons the activation of low‐threshold calcium spikes results in the amplification of synaptic responses.