bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anatomical Evidence for Rod Input to the Parvocellular Pathway in the Visual System of the Primate
Authors: Grünert Ulrike 
Published: April 2006

AbstractThe question whether midget bipolar cells in macaque monkey retina receive input from rods was investigated using double‐label immunocytochemistry. Flat midget bipolar cells (labelled with antibodies against recoverin) were found to be pre‐ and postsynaptic to All amacrine cells (labelled with antibodies against calretinin). These results support physiological evidence that rod photoreceptor signals could reach the parvocellular pathway at an early stage of visual processing.
Transient Up‐regulation of Ciliary Neurotrophic Factor Receptor‐α mRNA in Axotomized Rat Septa1 Neurons
Authors: Lee Mun‐Yong , Naumann Thomas , Kirsch Matthias , Frotscher Michael , Hofmann Hans‐Dieter 
Published: April 2006

AbstractUsing non‐radioactive in situ hybridization we investigated the effect of fimbria‐fornix transection on the expression of ciliary neurotrophic factor receptor α (CNTFRα) mRNA in axotomized septohippocampal neurons of the rat septal complex. Whereas CNTFRα expression was undetectable in the medial septal nucleus/diagonal band complex (MSDB) of control animals, specific up‐regulation was observed in MSDB neurons after fimbria‐fornix transection. CNTFRα expression was maximal 7–10 days after the lesion and had returned to control levels after 3 weeks. Following unilateral fimbria‐fornix transection, CNTFRα up‐regulation was restricted to the MSDB ipsilateral to the lesion. When cholinergic septal neurons were selectively eliminated by immunolesioning with 192 IgG‐saporin prior to fimbria‐fornix transection, the lesion‐induced expression of CNTFRα was still observed in many medial septal nucleus neurons. These results demonstrate that after fimbria‐fornix transection CNTFRα expression is transiently induced in axotomized, non‐cholinergic neurons of the medial septal nucleus, suggesting a postlesion function of locally supplied CNTF.
Relation Between Dendritic Ca2+ Levels and the Polarity of Synaptic Long‐term Modifications in Rat Visual Cortex Neurons
Authors: Hansel Christian , Artola Alain , Singer Wolf 
Published: April 2006

AbstractLong‐term changes of synaptic efficacy, in particular when they are use‐dependent, are candidate mechanisms for the storage of information in the nervous system. In a variety of brain structures, including the neocortex and hippocampus, synapses are susceptible to long‐term potentiation (LTP) and long‐term depression (LTD). It has been hypothesized that the polarity of the synaptic gain change depends on the amplitude of the postsynaptic [Ca2+]i rise, the threshold for the induction of LTD being lower than that for the induction of LTP. To test this assumption, we characterized Ca2+ signals in layer II/III pyramidal cells of rat visual cortex slices, using the fluorescent Ca2+ indicator fura‐2, during application of stimulation protocols that had been adjusted to reliably induce either LTP or LTD in cells not loaded with fura‐2. At dendritic sites activated by the stimulated afferents the intracellular [Ca2+] concentration ([Ca2+]i) reached higher amplitudes and decayed more slowly with stimuli inducing LTP than with those inducing LTD. To directly analyse the functional significance of the observed difference in the Ca2+ signal amplitude, we examined whether a tetanization protocol suitable for the induction of LTP can be converted into a protocol inducing LTD by injecting the postsynaptic cells with Ca2+ chelators that reduce the concentration of effective free Ca2+. In the presence of fura‐2 or BAPTA [bis(2‐aminophenoxy) ethane‐N,N,N′,N′‐tetraacetate], the stimulation protocol that would normally produce LTP induced either LTD or failed to induce synaptic modifications altogether. These results support the hypothesis that the amplitude of the postsynaptic rise in [Ca2+]i is a key factor in the determination of the polarity of synaptic gain change.
Deafferentation Weakens Excitatory Synapses in the Developing Central Auditory System
Authors: Kotak Vibhakar C. , Sanes Dan H. 
Published: April 2006

AbstractDecreased excitatory synaptic activity during development often leads to pre‐ and postsynaptic atrophy, as assessed anatomically. The present study considers the effect of decreased excitatory transmission on the maturation of synaptic strength. Towards this end, cochlear nucleus neurons, which project to the ipsilateral lateral superior olive (LSO), were denervated in gerbils at postnatal day 7, before the onset of hearing. This manipulation was intended to disrupt spontaneous glutamatergic transmission in the LSO while sparing the glycinergic afferents from the medial nucleus of the trapezoid body (MNTB). Afferent‐evoked synaptic activity was assessed 1–6 days after ablation in a brain slice preparation using whole‐cell current‐ and voltage‐clamp recordings. In control animals, ipsilaterally evoked excitatory postsynaptic potentials (EPSPs) were present in 91% of neurons tested, but were observed in only 60% of neurons following cochlea removal. The maximum EPSP amplitude was significantly smaller in manipulated neurons compared with controls, and this was accompanied by a higher incidence of ipsilaterally evoked inhibitory postsynaptic potentials (IPSPs). To study the efficacy of excitatory synapses in greater detail, voltage‐clamp recordings were made in the presence of strychnine and AP‐5 [d(O)‐2‐amino‐5‐phosphonopentanoic acid]. The minimum excitatory postsynaptic current (EPSC) amplitude, presumed to reflect the efficacy of a single glutamatergic afferent, was ∼40% smaller in manipulated neurons. In contrast, MNTB‐evoked IPSPs were similar in neurons from control and ablated animals. However, manipulated neurons often exhibited a rebound depolarization after a hyperpolarizing current pulse or an afferent‐evoked IPSP. In 70% of manipulated neurons, synaptically evoked rebound depolarizations were reduced, but not eliminated, by glutamate receptor antagonists. The glycine receptor antagonist strychnine did eliminate the IPSP‐associated depolarization in these neurons. Collectively, these results suggest that functional denervation of excitatory afferents decreases their synaptic efficacy as result of both cell loss as well as decreased strength of individual surviving synapses.
Regulation of Cholinesterase Gene Expression Affects Neuronal Differentiation as Revealed by Transfection Studies on Reaggregating Embryonic Chicken Retinal Cells
Authors: Robitzki Andrea , Mack Alexandra , Hoppe Ulrike , Chatonnet Arnaud , Layer Paul G. 
Published: April 2006

AbstractIn the embryonic chicken neuroepithelium, butyrylcholinesterase (BChE) as a proliferation marker and then acetylcholinesterase (AChE) as a differentiation marker are expressed in a mutually exclusive manner. These and other data indicate a coregulation of cholinesterase expression, and also possible roles of cholinesterases during neurogenesis. Here, both aspects are investigated by two independent transfection protocols of dissociated retina cells of the 6‐day‐old chick embryo in reaggregation culture, both protocols leading to efficient overexpression of AChE protein. The effect of the overexpressed AChE protein on the re‐establishment of retina‐like three‐dimensional networks (so‐called retinospheroids) was studied. In a first approach, we transfected retinospheroids with a pSVK3 expression vector into which a cDNA construct encoding the entire rabbit AChE gene had been inserted in sense orientation. As detected at the mRNA level, rabbit AChE was heterologously overexpressed in chicken retinospheroids. Remarkably, this was accompanied by a strong increase in endogenous chicken AChE protein, while the total AChE activity was only slightly increased. This increase was due to chicken enzyme, as shown by species‐specific inhibition studies using fasciculin. Clearly, total AChE activity is regulated post‐translationally. As an alternative method of AChE overexpression, transfection of spheroids was performed with an antisense‐5′‐BChE vector, which not only resulted in the down‐regulation of BChE expression, but also strongly increased chicken AChE transcripts, protein and enzyme activity. Histologically, a higher concentration of AChE protein (as a consequence of either AChE overexpression or BChE suppression) was associated with an advanced degree of tissue differentiation, as detected by immunostaining for the cytoskeletal protein vimentin.
Blockade of Basic Fibroblast Growth Factor Retards Recovery from Motor Cortex Injury in Rats
Authors: Rowntree Sharon , Kolb Bryan 
Published: April 2006

AbstractThe endogenous expression of basic fibroblast growth factor (bFGF) was blocked by neutralizing antibodies following unilateral suction lesions of the motor cortex. Rats with control treatment (saline, goat IgG) after motor cortex lesions showed slow recovery of forelimb manipulatory abilities. Rats with blockade of bFGF expression showed little recovery. Anatomically, the control‐treated lesioned rats showed an acute increase in bFGF and glial fibrillary acidic protein (GFAP) reactivity, and chronically they had normal dendritic arborization and spine density in layer V pyramidal cells in the remaining motor cortex. In contrast, rats treated with antibodies to bFGF showed little bFGF reactivity, normal GFAP reactivity, and atrophy of dendritic arbor and decreased spine density in layer V pyramidal cells. These results demonstrate the importance of endogenous bFGF release in processes related to functional recovery after cortical injury.
Comparison of the Expression of c‐fos, nur77 and egr1 mRNAs in Rat Hypothalamic Magnocellular Neurons and their Putative Afferent Projection Neurons: Cell‐ and Stimulus‐specific Induction
Authors: Luckman Simon M. 
Published: April 2006

AbstractHypothalamic magnocellular neurons and their afferent inputs provide a model system in which to study the regulation of inducible transcription factors in the brain in vivo. Osmotic stimulation of rats produced by graded infusions of saline at different tonicities was found to lead to the induction of c‐fos, nur77 and egr1 mRNAs in magnocellular neurons, as well as in putative afferent neurons, including those in structures of the forebrain (subfornical organ, median preoptic nucleus and organum vasculosum of the lamina terminalis). The results presented suggest that stronger levels of osmotic stimulation recruit additional afferents from the forebrain and brainstem that can act on magnocellular neurons via alternative receptors. A single systemic injection of the peptide cholecystokinin produced robust induction of c‐fos and nur77 mRNAs in afferent neurons of the brainstem nucleus tractus solitarii and in magnocellular neurons. Despite the fact that these two neuronal populations are clearly electrically active, egr1 was not induced by this stimulus, providing examples of cell‐ and stimulus‐specificity of its expression. This study re‐emphasizes that the induction of transcription factors is largely dependent on the nature of the afferent input and does not correlate necessarily to the electrical activity of the neuron.
Effect of Cerebellar Granule Cell Depletion on Learning of the Equilibrium Behaviour: Study in Postnatally X‐irradiated Rats
Authors: Le Marec N. , Stelz T. , Delhaye‐Bouchaud N. , Mariani J. , Caston J. 
Published: April 2006

AbstractTo assess the role of the mossy fibre‐granule cell pathway in learning, the cerebellum of young DA/HAN strain rats was irradiated to make the cortex completely or partially agranular. The X‐rays were delivered according to two different schedules, between 5–14 postnatal days (early group) and between 10–14 postnatal days (late group). Histological controls at 35 days showed a mean loss of granule cells of 96 ± 1% in the early group and of 61 ± 3% in the late group. The irradiated animals were subjected, from day 23 to day 35, to daily sensorimotor training on a rotorod. The scores and the strategy used (walking or hanging) by the rats were noted. The results demonstrate that a partial loss of granule cells due to a late X‐irradiation schedule induced mild motor disabilities but no learning deficit, the only problem being difficulty in elaborating rapidly an efficient strategy to solve a novel problem. A sub‐total loss of the granule cells, due to an early X‐irradiation schedule, induced gross motor disabilities and the animals used hanging >90% of the time. Due to the discrepancy between the learning abilities, which were preserved at least in part, and the gross motor impairments, the animals elaborated a novel strategy (jumping from the beam), allowing them to escape the experimental situation. This avoidance behaviour may be due to a decrease of anxiety, a lack of behavioural inhibition and/or attentional deficits that have been already observed in several other examples of cerebellar abnormalities.
AMPA Receptors are Coupled to the Nitric Oxide/Cyclic GMP Pathway in Cerebellar Astroglial Cells
Authors: Baltrons María Antonia , Garcia Agustina 
Published: April 2006

AbstractIn cultured rat cerebellar astroglia kainate induces cGMP formation with low potency (EC50 310 μM). In the presence of cyclothiazide, a blocker of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA) receptor desensitization, the effect of kainate was potentiated and glutamate and AMPA elicited large increases (>100‐fold) in cGMP levels. The response to all three agonists was abolished by the nitric oxide synthase inhibitor NG‐nitro‐L‐arginine and required extracellular calcium. Uptake of Co2+ was induced by AMPA in a limited population of astroglial cells and this effect was potentiated by cyclothiazide. These results indicate that calcium‐permeable AMPA receptors mediate stimulation of nitric oxide formation in cerebellar astroglia. This effect may be relevant for glutamate‐dependent synaptic plasticity processes in the cerebellum.
Cloning, Chromosomal Localization and Functional Expression of the Gene Encoding the α‐Subunit of the cG‐MP‐Gated Channel in Human Cone Photoreceptors
Authors: Wissinger Bernd , Müller Frank , Weyand Ingo , Schuffenhauer Simone , Thanos Solon , Kaupp U. Benjamin , Zrenner Eberhart 
Published: April 2006

AbstractCyclic nucleotide‐gated (CNG) ion channels serve as final targets of signal transduction in vertebrate photoreceptors. While the basic mechanisms of phototransduction are similar in rod and cone photoreceptors, both cell types express distinct sets of components of the transduction pathway. We report here the cloning of the cDNA encoding the α‐subunit of the cGMP‐gated channel of human cone photoreceptors. The open reading frame predicts a polypeptide of 694 amino acid residues with conserved functional parts and amino acid positions typical for the α‐subunit of CNG‐channels. Heterologous expression of the cDNA in Xenopus oocytes gave rise to cGMP‐gated channel activity. Antiserum directed against the C‐terminus of the bovine cone CNG channel α‐subunit crossreacted specifically with the heterologously expressed polypeptide and stained cone photoreceptors and weakly also the outer plexiform layer in human retinal sections. Northern blot analysis detected a prominent mRNA species of ∼3.8 kb in human retina. The entire gene spans ∼30 kb of genomic sequence and is located on the pericentric band q11.2 of human chromosome 2. The gene is composed of seven exons, with introns located at positions which are preserved with respect to the human rod gene, indicating a common ancestral gene structure. RT‐PCR analysis gave no evidence for alternatively spliced transcripts.
Neurotransmitter Modulation of Gap Junctional Communication in the Rat Hippocampus
Authors: Velazquez Jose L. Perez , Han Dan , Carlen Peter L. 
Published: April 2006

AbstractIncreasing experimental evidence indicates that gap junctions can be modulated by neurotransmitters, in particular dopamine. To examine possible modulation of gap junctional communication in the rat hippocampus by neurotransmitters, we studied dye coupling and electrotonic transmission in the CAI area in the presence of carbachol, a cholinergic agonist, and dopamine agonists. Carbachol markedly reduced dye coupling and the frequency of electrotonic potentials (spikelets). Spikelet amplitudes were decreased in the presence of carbachol. These effects were reversed by the cholinergic antagonist atropine, suggesting a muscarinic action of carbachol on gap junctional function. The non‐specific dopamine agonist apomorphine, and the specific D1receptor agonist SKF 38393, reduced dye coupling between pyramidal cells. Spikelet frequency was also decreased in the presence of dopamine agonists, but less than with carbachol. The specific D1receptor antagonist, SCH 23390, reversed the effects of both dopamine agonists. These observations indicate that cholinergic and dopaminergic transmission can affect electrical and chemical (dye coupling) communication through gap junctions, and could therefore alter properties of neuronal assemblies, in addition to their effects on intrinsic membrane properties.
In vivo Amygdala Dopamine Levels Modulate Cocaine Self‐administration Behaviour in the Rat: D1 Dopamine Receptor Involvement
Authors: Hurd Y. L. , McGrego A. , Pontén M. 
Published: April 2006

AbstractNucleus accumbens dopamine is often hypothesized as the critical factor for modulating cocaine self‐administration. In the current study we examined the extent to which dopamine in the amygdala could contribute to cocaine intake behaviour and modify nucleus accumbens dopamine levels. Rats were trained to self‐administer intravenous cocaine (1.5 mg/kg/injection) under a fixed‐ratio reinforcement schedule in daily 3 h operant training sessions. In the first in vivo microdialysis experiment, extracellular dopamine levels were found to be increased 200% of baseline in the amygdala and by 400% in the nucleus accumbens. Although cocaine induced similar profiles of dopamine overflow in the two mesolimbic areas, in the nucleus accumbens the latency of the dopaminergic response was shorter (three‐ to four‐fold) during both initiation and termination of the cocaine self‐administration session than in the amygdala. Despite achieving a stable self‐regulated pattern of cocaine intake and high dopamine concentrations in the nucleus accumbens, a unilateral injection of the D1 receptor antagonist SCH 23390 (0.5 or 1.5 μg) into the amygdala was still able to increase the rate of cocaine intake. This behavioural effect was accompanied by a dose‐dependent increase in nucleus accumbens dopamine levels; at the highest SCH 23390 concentration cocaine intake was increased by 400% and dopamine levels were potentiated by an additional 400%. In vivo autoradiography using [3H]SCH 23390 showed that D1 receptor sites contributing to the behavioural and subsequent neurochemical effects were predominantly localized to the amygdala and not the nucleus accumbens. Altogether these results point to a significant contribution of in vivo amygdala D1 dopamine transmission to cocaine self‐administration behaviour.
VEGF mRNA Induction Correlates With Changes in the Vascular Architecture Upon Spinal Cord Damage in the Rat
Authors: Bartholdi Deborah , Rubin Beatrix P. , Schwab Martin E. 
Published: April 2006

AbstractThe multiple cellular and molecular processes induced by injury to the central nervous system (CNS) are still poorly understood. In the present study, we investigated the response of the vasculature and the expression of mRNA for the angiogenic vascular endothelial growth factor (VEGF) following X‐irradiation of the spinal cord in the newborn and following traumatic spinal cord injury in the adult rat. Both lesion models induced changes in the density and the distribution pattern of blood vessels: while X‐irradiation led to a permanent local increase in vascular density in the fibre tracts of the exposed segments, a transient local sprouting of vessels was induced upon traumatic spinal cord injury. In situ hybridization showed that an increase of VEGF mRNA anticipated and overlapped with the vascular responses in both lesion models. In addition to the temporal correlation of VEGF expression and vascular sprouting, there was a clear correlation in the spatial distribution patterns. Following X‐irradiation, the expression of VEGF mRNA was restricted to the fibre tracts, precisely the areas where the changes in the vasculature were observed later on. Upon transection in the adult animal, VEGF was mainly detectable at the border of the lesion area, where the transient increase in vascular density could be observed. Interestingly, according to the type of lesion applied, astrocytes (X‐irradiation) or inflammatory cells (presumably microglial cells or macrophages; traumatic lesion) are the cellular sources of VEGF mRNA. Our results strongly indicate that VEGF is crucially involved in mediating vascular changes following different types of injury in the CNS.
Neurotrophins Stimulate Chemotaxis of Embryonic Cortical Neurons
Authors: Behar T. N. , Dugich‐Djordjevic M. M. , Li Y‐X. , Ma W. , Somogyi R. , Wen X. , Brown E. , Scott C. , McKay R. D. G. , Barker J. L. 
Published: April 2006

AbstractDuring mammalian cortical development, neuronal precursors proliferate within ventricular regions then migrate to their target destinations in the cortical plate, where they organize into layers. In the rat, most cortical neuronal migration occurs during the final week of gestation (Bayer et al., 1991; Jacobson, 1991). At this time (E15–E21), reverse transcriptase‐polymerase chain reaction demonstrated that cortical homogenates contain mRNA encoding brain derived neurotrophic factor (BDNF) and the catalytic form of its high‐affinity receptor, TrkB. lmmunocytochemistry and in situ hybridization of sections revealed that the catalytic TrkB receptors predominantly localize to regions containing migratory cells. Many TrkB+ cells exhibited the classic morphology of migrating neurons, suggesting that TrkB ligands play a role in cortical neuronal migration. We analysed whether TrkB ligands influence the motility of embryonic cortical cells (from E15–E21) using a quantitative in vitro chemotaxis assay. High‐affinity TrkB ligands (BDNF and NT4/5) stimulated chemotaxis (directed migration) of embryonic neurons at concentrations ranging from 1 to 100 ng/ml. NT‐3, a low‐affinity TrkB ligand, only stimulated significant migration at high concentrations (±100 ng/ml). Peak migration to BDNF was observed at gestational day 18 (E18). BDNF‐induced chemotaxis was blocked by either tyrosine kinase inhibitor, K252a, or the Ca2+‐chelator, BAPTA‐AM, suggesting that BDNF‐induces motility via autophosphorylation of TrkB receptor proteins and involves Ca2+‐dependent mechanisms. BDNF‐stimulation of increased cytosolic Ca2+ was confirmed with optical recordings of E18 cortical cells loaded with Ca2+ indicator dye. Thus, signal transduction through the TrkB receptor complex directs neuronal migration, suggesting that, in vivo, BDNF exerts chemotropic effects that are critical to morphogenesis of the cortex.