bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of Cerebral Blood Flow in the Human Auditory Cortex During Speech: Role of Motor‐to‐sensory Discharges
Authors: Paus Tomáš , Perry David W. , Zatorre Robert J. , Worsley Keith J. , Evans Alan C. 
Published: April 2006

AbstractTo investigate mechanisms of audio‐vocal interactions in the human brain, we studied the effect of speech output on modulation of neuronal activity in the auditory cortex. The modulation was assessed indirectly by measuring changes in cerebral blood flow (CBF) during unvoiced speech (whispering). Using positron emission tomography (PET), CBF was measured in eight volunteers as they uttered syllables at each of seven rates (30, 50, 70, 90, 110, 130 or 150/min) during each of the seven 60–s PET scans. Low‐intensity white noise was used throughout scanning to mask auditory input contingent on the whispering. We found that, as a function of the increasing syllable rate, CBF increased in the left primary face area, the upper pons, the left planum temporale and the left posterior perisylvian cortex. The latter two regions contain secondary auditory cortex and previously have been implicated in the processing of speech sounds. We conclude that, in the absence of speech‐contingent auditory input, the modulation of CBF in the auditory cortex is mediated by motor‐to‐sensory discharges. As such, it extends our previous findings of oculomotor corollary discharges to the audio‐vocal domain.
Differential Temporal Evolution of Post‐Training Changes in Regional Brain Glucose Metabolism Induced by Repeated Spatial Discrimination Training in Mice: Visualization of the Memory Consolidation Process?
Authors: Bontempi B. , Jaffard R. , Destrade C. 
Published: April 2006

AbstractThe present study analyses the effects of the stage of learning on the spatial patterns and time‐course of [14C] glucose uptake in BALB/c mice brain regions produced by spatial discrimination training in an eight‐arm radial maze. Our particular approach was designed to follow, during the post‐training period, the level of functional activity in individual brain areas which may underlie the memory consolidation process. Regional mapping of relative [14C] glucose uptake was assessed at three post‐training time intervals (5 min, 1 and 3 h) after either the first (Day 1), the fourth (Day 4) or the last (Day 9) daily training session of the discrimination task and compared with sham‐conditioned animals placed in the same experimental environment. The results indicated that numerous subcortical and cortical brain regions exhibit metabolic alterations following the acquisition of the spatial discrimination task. These alterations, which were specifically related to learning since they did not appear in sham‐conditioned animals, were functions both of the post‐training interval studied and of the degree of mastery of the task. On Day 1, a progressive, time‐dependent and sequential increase in labelling was found from subcortical (5 min post‐training) to cortical regions (3 h post‐training). On Day 4, a peak of cortical metabolic activation was identified at 1 h post‐training. In contrast, on Day 9, maximum labelling was found 5 min post‐training in all subcortical and cortical regions followed by a general monotonic decline at 1 and 3 h post‐training. These findings, which show widely distributed changes of metabolic activity in the brain, are consistent with the hypothesis that learning involves distributed neural networks. The sequential activation from subcortical to cortical regions seems to indicate a general mechanism whose function would ultimately be to store cortical memory representations. The acquisition‐dependent shifts in the patterns of post‐training metabolic labelling observed as a function of task mastery may be taken to represent a visualization of the spatio‐temporal evolution of the networks of brain structures actively engaged in the memory consolidation process. In particular, the present data suggest that the duration of post‐acquisition memory processing is a function of the quantity of new information which has to be dealt with by the central nervous system.
Neuronal Nicotinic Receptor a6 Subunit mRNA is Selectively Concentrated in Catecholaminergic Nuclei of the Rat Brain
Authors: Le Novere Nicolas , Zoli Michele , Changeux Jean‐Pierre 
Published: April 2006

AbstractAlthough the neuronal nicotinic receptor a6 subunit was cloned several years ago, its functional significance remains to be investigated. Here we describe an in situ hybridization study of the mRNA for this subunit in the adult rat central nervous system using oligonucleotide probes. Specific a6 mRNA labelling was restricted to a few nuclei throughout the brain; it was particularly high in several catecholaminergic nuclei [the locus coeruleus (A6), the ventral tegmental area (A10) and the substantia nigra (A9)] at levels significantly higher than those found for any other known nicotinic receptor subunit mRNA. Labelling for a6 mRNA was also detected at lower levels in the reticular thalamic nucleus, the supramammillary nucleus and the mesencephalic V nucleus. Some cells of the medial habenula (medioventral part) and of the interpeduncular nucleus (central and lateral parts) were also labelled. The distribution of a6 mRNA was compared with the distribution of the other known nicotinic acetylcholine receptor subunit mRNAs. In several nuclei, the expression of a6 was complementary to those of other a subunits. Moreover, some of the cell groups (such as the substantia nigra, the ventral tegmental area and the locus coeruleus) previously thought to contain mainly a3 mRNA in fact were found to contain high levels of α6 mRNA. Finally, we found extensive colocalization of α6 and p3, indicating the possible existence of nicotinic receptor hetero‐oligomers containing both subunits. The present results show that a6 is the major nicotinic acetylcholine receptor a subunit expressed in dopaminergic cell groups of the mesencephalon and noradrenergic cells of the locus coeruleus. This suggests the involvement of the a6 subunit in some of the major functions of central nicotinic circuits, including the modulation of locomotor behaviour and reward.
The Role of Spinal Neurokinin‐2 Receptors in the Processing of Nociceptive Information from the Joint and in the Generation and Maintenance of Inflammation‐evoked Hyperexcitability of Dorsal Horn Neurons in the Rat
Authors: Neugebauer V. , Rümenapp P. , Schaible H.‐G. 
Published: April 2006

AbstractIn spinal cord neurons in anesthetized rats, the role of neurokinin A and neurokinin‐2 receptors in the processing of nociceptive information from the knee joint was studied. The specific non‐peptide antagonist at the neurokinin‐2 receptor, SR48968, its inactive R‐enantiomer, SR48965, neurokinin A, substance P and (R, S)‐α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA), were administered ionophoretically close to neurons with input from the knee joint. SR48968 reduced the effects of exogenous neurokinin A, but not those of exogenous substance P and AMPA, indicating selective blockade of neurokinin‐2 receptors. In most neurons with input from the normal knee joint, SR48968 reduced dose‐dependently the responses to noxious pressure applied to the knee, and in ˜50% of the neurons the responses to innocuous pressure. The administration of SR48968 during the induction of an experimental joint inflammation markedly attenuated the development of inflammation‐evoked hyperexcitability. In hyperexcitable neurons with input from the inflamed joint, SR48968 reduced the responses to noxious and innocuous pressure. The relative reduction of the responses was more pronounced than in neurons with input from the normal joint. None of the effects of SR48968 was mimicked by SR48965. These data show that neurokinin‐2 receptors are involved in the spinal processing of nociceptive information from the normal joint. Furthermore, neurokinin‐2 receptors must be coactivated at an early stage of inflammation, to allow the generation of hyperexcitability. Finally, neurokinin‐2 receptors are involved in the maintenance of hyperexcitability during inflammation. In summary, spinal neurokinin‐2 receptors are important in the generation of pain in the normal and inflamed joint.
Neurotrophin‐4/5 Maintains the Cholinergic Phenotype of Axotomized Septal Neurons
Authors: Alderson Ralph F. , Wiegand Stanley J. , Anderson Keith D. , Cai Ning , Cho Jae‐Young , Lindsay Ronald M. , Altar C. Anthony 
Published: April 2006

AbstractWe examined the effect of intraseptal or intracerebroventricular (i.c.v.) infusions of NT‐4/5 or intraseptal infusions of NGF on the level of immunohistochemical staining of choline acetyltransferase (ChAT) and the low‐affinity nerve growth factor receptor (LNGFR) in the rat medial septum following unilateral transection of the fimbria. The extent of cell loss in the septum ipsilateral to the lesion, determined by cell counts of ChAT‐immunopositive neurons and expressed as a ratio comparing the lesioned to the intact sides, was 0.28 in animals that received an infusion of phosphate‐buffered saline (PBS). The ratios were 0.97 and 1.07 in animals that received an infusion of NT‐4/5 into the ipsilateral ventricle and septum respectively. Septal infusions of NGF produced a ratio of ChAT‐immunopositive cells of 1.03. The ratios of LNGFR‐immunopositive neurons increased from 0.50 in PBS‐infused animals to 0.79 and 0.83 in animals infused with NT‐4/5 via the i.c.v. and septal routes respectively, and to 0.89 with NGF via the septal route. Transection of the fimbria also reduced the expression of TrkA in the ipsilateral medial septum and vertical limb of the diagonal band of Broca in PBS‐infused animals. The loss of TrkA was ameliorated by either i.c.v. infusion of NT‐4/5 or septal infusion of NT‐4/5 or NGF. As determined by immunohistochemical staining, NT‐4/5 infused into the lateral ventricle was detected in the periventricular portions of the forebrain ipsilateral to the infusion, while NT‐4/5 or NGF infused intraseptally was detected in much of the septum, bilaterally. Furthermore, exogenous NT‐4/5 or NGF was detected in numerous neuronal perikarya in the medial septal and diagonal band nuclei. These data demonstrate that, as with NGF, i.c.v. as well as septal infusions of NT‐4/5 can maintain the phenotype of basal forebrain cholinergic neurons following axotomy.
Leukaemia Inhibitory Factor or Related Factors Promote the Differentiation of Neuronal and Astrocytic Precursors within the Developing Murine Spinal Cord
Authors: Richards Linda J. , Kilpatrick Trevor J. , Dutton Renee , Tan Seong‐Seng , Gearing David P. , Bartlett Perry F. , Murphy Mark 
Published: April 2006

AbstractPreviously we have shown that leukaemia inhibitory factor (LIF) potentiates the development of murine spinal cord neurons in vitro, suggesting that it, or related factors, may play an important regulatory role in neuronal development. We have further investigated this role and show here that the generation of neurons in cultures of embryonic day 10 spinal cord cells is inhibited by antibodies to the β subunit of the LIF receptor. Since there are more undifferentiated precursors in antibody‐treated cultures than in control and LIF‐treated cultures, it is concluded that the primary action of LIF, or related molecules, is to promote neuronal differentiation, not precursor survival. In addition, the failure of LIF to support neuronal survival in the period immediately following differentiation suggests that the increased numbers of neurons generated with LIF are not attributable to its neurotrophic action. By selecting neuronal precursors on the basis of their inability to express class I major histocompatibility complex molecules, it was shown that LIF acted directly upon these cells and not via an intermediary cell. LIF also appears to be involved in regulating the differentiation of astrocytes, since it increases the number of glial fibrillary protein (GFAP)‐positive cells present in the cultures and since the spontaneous production of GFAP‐positive cells is blocked by antibodies to the LIF β receptor. These findings suggest that LIF or related factors promote the differentiation of neural precursors in the spinal cord, but that they are not involved in preferentially promoting precursors down a specific differentiation pathway.
Effects of Repeated Sensory Stimulation (Electro‐acupuncture) and Physical Exercise (Running) on Open‐field Behaviour and Concentrations of Neuropeptides in the Hippocampus in WKY and SHR rats
Authors: Bucinskaite Violeta , Theodorsson Elvar , Crumpton Kevin , Stenfors Carina , Ekblom Anders , Lundeberg Thomas 
Published: April 2006

AbstractThe effects of repeated sensory stimulation (electro‐acupuncture) and physical exercise (running) on open‐field behaviour and on hippocampal concentrations of neuropeptide Y, neurokinin A, substance P, galanin and vasoactive intestinal peptide (VIP)‐like immunoreactivities were studied in WKY (Wistar‐Kyoto) and SHR (spontaneously hypertensive) rats. Significantly higher concentrations of substance P‐like immunoreactivity, neurokinin A‐like immunoreactivity and neuropeptide Y‐like immunoreactivity were found in the hippocampus immediately after 3 weeks of treatment (electro‐acupuncture and running), but not 1 week after the last (tenth) intervention. No changes in galanin‐like immunoreactivity and VIP‐like immunoreactivity were found. The changes in neuropeptide concentrations were similar in the two rat strains. Open‐field behaviour was significantly reduced during the treatment period in both strains. There were significant negative correlations between behaviour and neuropeptide concentrations in SHR rats, suggesting interdependency with sympathetic activity. It is proposed that the effects of electro‐acupuncture and physical exercise in rats are related to increases in neuropeptide Y, neurokinin A and substance P in the hippocampus.
Acquisition of Conditioned Inhibition in Rats is Impaired by Ablation of Serotoninergic Pathways
Authors: Lister Sarah , Pearce John M. , Butcher Steven P. , Collard Keith J. , Foster George A. 
Published: April 2006

AbstractThe effects of chronically ablating the serotoninergic inputs to various regions of the rat brain on the ability to solve a feature‐negative discrimination was measured. After intracerebroventricular administration of the specific neurotoxin 5, 7‐dihydroxytryptamine, the rats exhibited an impaired capacity to solve such a discrimination, irrespective of whether auditory or visual stimuli were used. Further behavioural analysis revealed that this effect was not due to a reduced capacity to form excitatory associations, since both groups responded equally to reinforced stimuli. By contrast, the lesion more likely resulted in a failure to endow the non‐reinforced stimuli with inhibitory properties. This suggestion was supported by the observation that, in a retardation test, the conditioned inhibitor aroused less inhibition in the lesioned group than in vehicle‐injected controls. Furthermore, the conditioned inhibitor failed to pass a summation test in lesioned animals, again indicating that their hampered ability to master the discrimination was the result of an impairment in the formation of inhibitory associations. It is concluded that destruction of central 5‐hydroxytryptamine‐containing pathways impairs the functioning of brain areas underlying inhibitory associative learning.
Comparative Patch‐clamp Studies with Freshly Dissociated Rat Hippocampal and Striatal Neurons on the NMDA Receptor Antagonistic Effects of Amantadine and Memantine
Authors: Parsons C. G. , Panchenko V. A. , Pinchenko V. O. , Tsyndrenko A. Y. , Krishtal O. A. 
Published: April 2006

AbstractPatch‐ and concentration‐clamp techniques were used to compare the effects of the uncompetitive N‐methyl‐D‐aspartate (NMDA) receptor antagonists (+)‐MK‐801 (dizocilpine, (+)‐5‐methyl‐10, 11‐dihydro‐5H‐dibenzo‐cyclohepten‐5, 10‐imine maleate), ketamine, memantine (1‐amino‐3, 5‐dimethyladamantane) and amantadine (1‐amino‐adamantane) on agonist‐induced inward currents in freshly dissociated rat hippocampal and striatal neurons. In hippocampal neurons, ketamine (5 μM), memantine (10 μM) and amantadine (100 μM) selectively antagonized inward current responses to NMDA (500 μM plus glycine 5 μM) in a voltage‐dependent manner without affecting responses to (s)‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazoleproprionic acid (100 μM) or γ‐aminobutyric acid (10 μM). The NMDA receptor antagonistic effect of all four agents was typical of open channel blockade. The kinetics of blockade/unblockade was inversely related to antagonist affinity. In hippocampal neurons amantadine was the least potent NMDA receptor antagonist (IC50 18.6 ± 0.9 μM) and showed the fastest blocking kinetics, whereas (+)‐MK‐801 was the most potent (IC50 0.12 ± 0.01 μM) and showed the slowest blocking kinetics. Memantine (IC50 1.04 ± 0.26 μM) and ketamine (IC50 0.43 ± 0.10 μM) were almost equipotent and had similar, intermediate blocking kinetics. In striatal neurons recorded under identical conditions (+)‐MK‐801, ketamine and memantine were 3‐ to 4‐fold less potent whereas amantadine was somewhat more potent than on hippocampal neurons. This could offer an explanation for the better clinical profile of amantadine in Parkinson's disease, as therapeutically relevant concentrations of amantadine are likely to be more active in the striatum whereas memantine is likely to be more active in other structures.
Triiodothyronine Exerts a Trophic Action on Rat Sensory Neuron Survival and Neurite Outgrowth through Different Pathways
Authors: Walter I. Barakat 
Published: April 2006

AbstractApart from several growth factors which play a crucial role in the survival and development of the central and peripheral nervous systems, thyroid hormones can affect different processes involved in the differentiation and maturation of neurons. The present study was initiated to determine whether triiodothyronine (T3) affects the survival and neurite outgrowth of primary sensory neurons in vitro. Dorsal root ganglia (DRG) from 19‐day‐old embryos or newborn rats were plated in explant or dissociated cell cultures. The effect of T3 on neuron survival was tested, either in mixed DRG cell cultures, where neurons grow with non‐neuronal cells, or in neuron‐enriched cultures where non‐neuronal cells were eliminated at the outset. T3, in physiological concentrations, promoted the growth of neurons in mixed DRG cell cultures as well as in neuron‐enriched cultures without added nerve growth factor (NGF). Since neuron survival in neuron‐enriched cultures cannot be promoted by endogenous neurotrophic factors synthesized by non‐neuronal cells, the increased number of surviving neurons was due to a direct trophic action of T3. Another trophic effect was revealed in this study: T3 sustained the neurite outgrowth of sensory neurons in DRG explants. The stimulatory effect of T3 on nerve fibre outgrowth was considerably reduced when non‐neuronal cell proliferation was inhibited by the antimitotic agent cytosine arabinoside, and was completely suppressed when the great majority of non‐neuronal cells were eliminated in neuron‐enriched cultures. These results indicate that the stimulatory effect of T3 on neurite outgrowth is mediated through non‐neuronal cells. It is conceivable that T3 up‐regulates Schwann cell expression of a neurotrophic factor, which in turn stimulates axon growth of sensory neurons. Together, these results demonstrate that T3 promotes both survival and neurite outgrowth of primary sensory neurons in DRG cell cultures. The trophic actions of T3 on neuron survival and neurite outgrowth operate under two different pathways.
Calcium Channels in Neuroblastoma Cell Growth Cones
Authors: Zimprich Fritz , Bolsover Stephen R. 
Published: April 2006

AbstractThe concentration of free calcium ions in the cytosol has been shown to influence many components of growth cone behaviour, including the extension of filopodia and veils, the addition of new membrane to the plasmalemma, the retraction and disappearance of filopodia, and gross collapse and retraction of the growth cone. A spatially localized modulation of these processes by very local calcium changes has been proposed to underlie the steering of growth cones by gradients of neurotransmitters, voltage and cell adhesion molecules. Such local control can be studied in mouse neuroblastoma cells, where depolarization causes calcium to rise in a limited number of spatially restricted hotspots, triggering a localized advance. We have studied the simple, club‐shaped growth cones that are characteristically found on advancing neurites. Depolarization caused calcium to increase most at the distal, leading tip. Agents that disrupt calcium‐induced calcium release do not affect growth cone calcium dynamics, ruling out a local release of calcium at the tip as a cause of the gradient. Using cell‐attached patch recording, we find that L‐type calcium channels are present at a higher density at the distal tip than in the proximal growth cone. Our results show that the calcium gradients seen in depolarized growth cones are a direct consequence of a gradient of calcium channel density.
Decreased Expression of TrkB and TrkC mRNAs in Spinal Motoneurons of Aged Rats
Authors: Johnson Hans , Hökfelt Tomas , Ulfhake Brun 
Published: April 2006

AbstractSeveral studies have indicated that a decrease in availability and/or responsiveness to neurotrophin(s) may be of importance in ageing and disease‐related neurodegeneration. Using in situ hybridization we have studied the mRNA expression of the full‐length neurotrophin receptors TrkB and TrkC in spinal cord motoneurons of aged rats (30 months old) with symptoms of hindlimb incapacity and in young adult rats (2–3 months old). The labelling intensity for TrkB of the individual cell profile was decreased by 25% (P < 0.001) in both the cervical and lumbar motor nuclei of aged rats. In thoracic motoneurons of aged and young adult rats the difference in expression of TrkB mRNA was smaller (down by 15%; P < 0.05). The labelling for TrkC mRNA was much weaker than that for TrkB in both aged and young adult rats, but TrkC mRNA expression also seemed to decrease. Comparison of the different motor nuclei along the spinal cord axis revealed that the motoneurons of the L6/S1 nuclei showed the strongest hybridization signal for the two Trk receptors in both aged and young adult rats. The possibility that a decrease in TrkB mRNA may contribute to age‐related motor disturbances is discussed.