bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopaminergic Modulation of Transient Neurite Outgrowth from Horizontal Cells of the Fish Retina is not Mediated by cAMP
Authors: Kohler Konrad , Weiler Reto
Published: April 2006

Horizontal cell dendrites invaginating the cone pedicles in the fish retina exhibit a marked light dependent plasticity in the morphology of their synaptic connections. Upon light adaptation of the retina, numerous spinules are formed which disappear during dark adaptation. This process is paralleled by a strengthening and weakening, respectively, of the horizontal cell's inhibitory output. The formation of spinules during light adaptation requires dopaminergic activity as it does not occur in dopamine‐depleted retinas, but can be partially induced in depleted retinas by the exogenous administration of dopamine. Although horizontal cells do have D1 receptors the action of dopamine is not coupled to a stimulation of cAMP. An increase of intracellular cAMP either by injection of a cAMP analogue or by metabolic interference does not result in any spinule formation. The data suggest that dopamine must act through a cAMP independent intracellular mechanism.
Evidence that Very Slow Wallerian Degeneration in C57BL/Ola Mice is an Intrinsic Property of the Peripheral Nerve
Authors: Perry V. H. , Brown M. C. , Lunn E. R. , Tree P. , Gordon S.
Published: April 2006

We have described a mutant mouse, C57BL/Ola, in which Wallerian degeneration following peripheral nerve transection is very slow. Our previous results suggested that recruited monocytes play a role in rapid Wallerian degeneration. The nature of the mutation in C57BL/Ola mice is not known and we have investigated whether the defect is intrinsic to the nerve or due to a defect in the circulating monocytes. We have made chimaeric mice in which bone marrow from histocompatible mice, with rapidly degenerating nerves and normal monocyte recruitment, was used to reconstitute irradiated C57BL/Ola mice and vice‐versa. A substantial degree of donor repopulation of the hosts was confirmed by measures of the levels of glucose‐phosphate isomerase alloenzymes in blood and tissue samples from the two different strains. The rate of degeneration of the transected sciatic nerve was found to be host‐dependent, providing evidence that the mutation affects cell populations intrinsic to the nerve and not the circulating monocytes. We provide additional evidence that the peripheral nerves of C57BL/Ola mice are different from those of other mice as they degenerate at a slower rate in vitro.
Transferrin Receptor Expression and Iron Uptake in the Injured and Regenerating Rat Sciatic Nerve
Authors: Raivich G. , Graeber M. B. , Gehrmann J. , Kreutzberg G. W.
Published: April 2006

Iron‐saturated transferrin is a ubiquitous growth factor that plays a critical role in cellular iron uptake, growth and proliferation. Here we have studied the expression and distribution of transferrin receptors and iron uptake following injury of the rat sciatic nerve. Axotomy led to a massive but transient increase (days 2–9, maximum day 4) in [125l]transferrin binding at the site of the injury and in the distal, denervated part of the crushed or resected sciatic nerve, shortly preceding the time course of cellular proliferation (Friede and Johnstone, Acta Neuropathol, 7, 218–231, 1967; Jurecka et al., Acta Neuropathol, 32, 299–312, 1975). An additional, transient increase in specific binding was observed during reinnervation after reconnection of the resected sciatic nerve. Immunocytochemistry using the Ox‐26 monoclonal antibody revealed strong and simultaneous expression of the transferrin receptor protein on two different cell types: on a subpopulation of blood‐borne macrophages invading the injured peripheral nerve and on Schwann cells reacting to denervation and reinnervation. In addition, studies using intravenously injected radioactive iron (59Fe3+) showed a massive increase in endoneural iron uptake confined to the lesion site and to the distal part of the axotomised sciatic nerve, parallel to the time course of reactive transferrin receptor expression. Since iron is an essential cofactor of a number of key enzymes needed in energy metabolism and DNA synthesis, these data suggest that the induction of transferrin receptor expression may play an important role in the regulation of cellular growth and proliferation during peripheral nerve regeneration.
Striatal Ascorbate and its Relationship to Dopamine Receptor Stimulation and Motor Activity
Authors: Zetterström Tyra , Wheeler David B. , Boutelle Martyn G. , Fillenz Marianne
Published: April 2006

We have used the techniques of microdialysis and in vivo voltammetry to monitor striatal dopamine and ascorbate, as well as motor activity in unanaesthetized, freely‐moving rats. Systemic administration of the non‐selective dopamine receptor agonist apomorphine (0.5 mg/kg, s.c.) caused a decrease in dopamine, an increase in ascorbate, stereotyped behaviour and a generalized increase in motor activity. Separate systemic applications of the D2 receptor agonist SKF 38393 (10 mg/kg, s.c.) and the D2 receptor agonist Quinpirole (0.1 mg/kg s.c.) caused a decrease in dopamine but had no effect on ascorbate or motor activity. After coadministration of these drugs, there was an increase in both ascorbate and motor activity. Local application of apomorphine (0.01 mM) caused a reduction in dopamine similar to that seen following systemic application but had no effect on ascorbate or motor activity. The present results demonstrate that dopamine, via D1 and D2 receptors outside the striatum, plays an important role in the control of ascorbate release. These results lend further support to the hypothesis that changes in ascorbate levels are an index of glutamatergic neurotransmission.
The Effects of Activation or Inhibition of the Subthalamic Nucleus on the Metabolic and Electrophysiological Activities Within the Pallidal Complex and Substantia Nigra in the Rat
Authors: Féger Jean , Robledo Patricia
Published: April 2006

The changes in local cerebral glucose utilization (LCGU) and neuronal unit activities in the subthalamic nucleus and its major target structures (the pars reticulata of the substantia nigra, the globus pallidus and the entopeduncular nucleus) following microinjection of a GABAergic antagonist (bicuculline methiodide, 0.08 nmol) or agonist (muscimol, 0.2 nmol) into the subthalamic nucleus were determined. The metabolic effect was assessed by measuring LCGU by quantitative [14C]‐2‐deoxyglucose autoradiography in ketamine‐anaesthetized rats. Bicuculline methiodide induced increased LCGU in the ipsilateral globus pallidus, the entopeduncular nucleus and the substantia nigra pars reticulata. In contrast, muscimol decreased LCGU in these structures. The neuronal activities in the subthalamic nucleus and related structures increased following injection of bicuculline and decreased after injection of muscimol. The changes in LCGU within the structures directly related to the subthalamic nucleus were correlated with the changes in the unit activity either in the subthalamic nucleus and/or its projection structures. However, the amplitude of the relative changes in neuronal unit activity were greater than the changes in LCGU. Nevertheless, the results emphasize the functional role of the subthalamic nucleus as an activating structure within the basal ganglia.
Excitatory Actions of the Metabotropic Excitatory Amino Acid Receptor Agonist, trans‐(±)‐1‐amino‐cyclopentane‐1,3‐dicarboxylate (t‐ACPD), on Rat Thalamic Neurons In Vivo
Authors: Salt T. E. , Eaton S. A.
Published: April 2006

The metabotropic excitatory amino acid receptor agonist trans‐(±)‐1‐amino‐cyclopentane‐1,3‐dicarboxylate (t‐ACPD) was applied to rat ventrobasal thalamic neurons by iontophoresis. This agonist typically evoked an excitatory response which was slower in onset and of longer duration than responses to the other excitatory amino acid agonists, N‐methyl‐aspartate, kainate or (R.S)‐a‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate. Responses to f‐ACPD were resistant to the excitatory amino acid antagonists 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione, 3‐((RS)‐2‐carboxypiperazin‐4‐yl)‐propyl‐1‐phosphonic acid and kynurenate. These results suggest that f‐ACPD may exert its effects via the so‐called ‘metabotropic’ excitatory amino acid receptor. The putative antagonists at this receptor, D‐2‐amino‐4‐phosphono‐butyrate (D‐AP4), L‐2‐amino‐4‐phosphono‐butyrate (L‐AP4) and L‐2‐amino‐3‐phosphono‐propionate (L‐AP3), were able to reduce responses to t‐ACPD under certain circumstances. However, such antagonism was always accompanied by similar reductions in excitatory responses to other agonists. These non‐selective effects would appear to limit the usefulness of AP4 and AP3 as antagonists of t‐ACPD.
Dorsal Horn Plasticity Following Re‐routeing of Peripheral Nerves: Evidence for Tissue‐Specific Neurotrophic Influences from the Periphery
Authors: Lewin Gary R. , McMahon Stephen B.
Published: April 2006

Some properties of primary sensory neurons change when they reinnervate new peripheral targets (McMahon et al., Neuroscience, 33, 67–75, 1989). We ask here if such influences can extend to the central connectivity of sensory neurons. In adult rats the nerve to the gastrocnemius muscle (GN) and the cutaneous sural nerve (SN) were self‐ and cross‐anastomosed on left‐ and right‐hand sides, respectively, so that they regenerated to either appropriate or inappropriate targets. Ten to 14 weeks later, the distribution and strength of spinal connections of the SN and GN were determined. The unmyelinated afferents in the GN innervating skin increased their connectivity to 286% of that seen for the GN innervating muscle (P < 0.005), and came to resemble normal cutaneous afferents. However, for the SN there was no significant difference between appropriately and inappropriately regenerated nerves by this measure. The ability of myelinated fibres to produce inhibitions and facilitations in dorsal horn cells was also assessed. The intact or self‐anastomosed SN produced predominantly inhibitory effects, whilst the GN produced predominantly facilitatory effects. After the SN had regenerated to muscle its central effects became predominantly facilitatory, whilst those of the GN innervating skin became inhibitory. These changes were statistically significant. In conclusion, we have found that major changes in the physiology of central connections in the dorsal horn may occur following peripheral reinnervation of foreign targets. The changes that were seen were appropriate to the new target, and could not easily be explained by non‐specific changes due to axotomy, or changes in A‐fibre‐mediated inhibitions. We suggest that these effects might arise because of trophic influences arising in and specific to different peripheral targets.
GABA‐Mediated Presynaptic Inhibition in Crayfish Primary Afferents by Non‐A, Non‐B GABA Receptors
Authors: El Manira A. , Clarac F.
Published: April 2006

GABAergic presynaptic inhibition has been investigated in primary afferents using an in vitro preparation of the crayfish, Procambarus clarkii. Presynaptic terminals of a leg proprioceptor, the coxo‐basal (CB) chordotonal organ, were impaled in the neuorpil of the 5th thoracic ganglion. Pressure ejection of small volumes of the GABAA or GABAB receptor agonists, muscimol and 3‐aminopropylphosphinic acid (3‐APA), both induce depolarizing responses in the impaled CB sensory terminal. These depolarizations are not blocked by the specific GABAA and GABAB receptor antagonists, SR‐95531 and phaclofen, but they are abolished by picrotoxin. Both muscimol‐ and 3‐APA‐induced depolarizations are carried by an increase in conductance to Cl‐. The presynaptic increase in conductance to C1‐ by GABA receptor activation leads to a depression of sensory synaptic transmission through a shunting of the incoming spikes. Monosynaptic EPSPs elicited in motor neurons by CB sensory nerve stimulation are depressed by muscimol and 3‐APA. GABA‐mediated presynaptic modulation occurs in crayfish primary afferents which can adjust the gain of reflexes. These results show that GABA‐activated Cl‐ channels can induce a modulation of synaptic transmission, but also that the distinction between GABAA and GABAB receptors, as in vertebrates, is not applicable to the crustacean primary afferents.
Activation of AP5‐sensitive NMDA Receptors is Not Required to Induce LTP of Synaptic Transmission in the Lateral Perforant Path
Authors: Bramham Clive R. , Milgram N. W. , Srebro Bolek
Published: April 2006

The role of the N‐methyl‐D‐aspartate (NMDA) type of glutamate receptor in long‐term potentiation (LTP) of the medial (MPP) and lateral (LPP) divisions of the perforant path‐granule cell system was investigated in urethane‐anaesthetized rats. A stimulating electrode was positioned in the dorsomedial or ventrolateral aspect of the angular bundle for selective activation of either the MPP or LPP, respectively. A push‐pull cannula served to focally perfuse artificial cerebrospinal fluid (ACSF) across the perforant path synaptic zone, while evoked potentials were monitored in the dentate hilus. Identification of LPP and MPP responses was based on (1) differences in population excitatory postsynaptic potential (EPSP) waveform obtained during stimulus depth profiles, and (2) differential sensitivity of evoked EPSPs to the glutamate receptor agonist L‐aminophosphonobutyrate (AP4), and the antagonist γ‐D‐glutamylglycine (DGG). High‐frequency stimulation (400 Hz, 8 bursts of 8 pulses) applied to the lateral and medial perforant path elicited LTP of the EPSP and population spike in rats perfused with standard medium. In the MPP, LTP was almost completely blocked when D‐aminophosphonopentanoate (AP5; 100 μM), a selective NMDA receptor antagonist, was perfused during the tetanus. Surprisingly, in the LPP experiments, AP5 did not impair induction of the ‘synaptic’ EPSP component of LTP. This occurred despite the ability of AP5 to block LTP of the LPP evoked population spike. The results suggest the existence of a novel, NMDA receptor‐independent form of synaptic LTP in the lateral perforant path.
Learning‐induced Increase of Immediate Early Gene Messenger RNA in the Chick Forebrain
Authors: Anokhin Konstantin V. , Rose Steven P. R.
Published: April 2006

The immediate early genes c‐fos and c‐jun are activated rapidly in nerve cells in response to in vivo and in vitro stimulation. Because of their involvement in transcriptional regulation, the products of these genes have been proposed as nuclear signals for consolidation of long‐term memory. However, no specific changes of immediate early gene expression in relation to learning have yet been reported. Compared with quiet controls, training young chicks to discriminate food grains from inedible pebbles results in a 4.8‐fold elevation of c‐fos and a 3.7‐fold elevation of c‐jun mRNA in the forebrain 30 min after an 8‐min training session. Compared to chicks that had learned the discrimination and were merely repeating already learned behaviour, the increase in c‐jun mRNA in the learning group was 64% (P < 0.03) but a 24% increase in c‐fos mRNA was not significant. Because the increased expression is higher in birds that are learning the task than in those that are repeating already learned behaviour, and is not proportional to behavioural activity per se, we conclude that learning a new task is itself responsible for enhanced expression of the genes.
Effect of Climbing Fibre Deprivation on the K+‐evoked Release of Endogenous Adenosine from Rat Cerebellar Slices
Authors: Do Kim Quang , Vollenweider Franz X. , Zollinger Markus , Cuénod Michel
Published: April 2006

We report the identification of a compound whose K+‐induced Ca2+‐dependent release in rat cerebellar slices was reduced following climbing fibre deprivation by 3‐acetylpyridine8 (3‐AP) treatment. Based on HPLC retention time, UV absorption spectrum, and mass spectrometry, this compound was identified as adenosine. The K+‐induced, Ca2+‐dependent release of adenosine was subsequently quantified in control and 3‐AP‐treated rats. It decreased by 60–70% in both the cerebellar vermis and hemispheres following climbing fibre deprivation, while 3‐AP treatment had no effect on adenosine release in the cerebral cortex. Inhibition of ecto‐5′‐nucleotidase by α,β‐methylene ADP and GMP decreased basal and stimulated efflux of adenosine in the cerebellum by 50–60%, indicating that a Significant proportion of adenosine was derived from the extracellular metabolism of released nucleotides. Taken with the reports of other groups on adenosine in cerebellum, these results suggest that climbing fibre activity increases the extracellular level of adenosine, probably through the metabolism of released nucleotides. This adenosine could then cause presynaptic inhibition of the release of the parallel fibre transmitter, which is presumably glutamate. This may account for the climbing fibre‐evoked depression of Purkinje cell sensitivity to parallel fibre input.
Cerebral Glycoprotein Synthesis and Long‐term Memory Formation in the Chick (Gallus domesticus) Following Passive Avoidance Training Depends on the Nature of the Aversive Stimulus
Authors: Bourne R. C. , Davies D. C. , Stewart M. G. , Csillag A. , Cooper M.
Published: April 2006

Chicks that peck a small bright bead coated in a distasteful substance can learn in a single trial to subsequently avoid a similar bead. The taste aversant commonly used is methyl anthranilate, which also has a strong pervasive odour. We have compared the efficacy of methyl anthranilate and the apparently odourless quinine as aversants. Methyl anthranilate‐trained chicks learnt the task and the memory apparently persisted undiminished for at least 24 h. Quinine‐trained chicks exhibited a memory for the task similar to that of methyl anthranilate‐trained chicks 45 min after training, this thereafter declined until, at 24 h after training, they showed no recall. We investigated the incorporation of a radio‐labelled synaptic membrane glycoprotein precursor, [3H]fucose, into three regions of the chick forebrain; two of these regions have previously been implicated in learning using methyl anthranilate as the aversant. There was a significant increase in [3H]fucose incorporation into the left lateral cerebral area and numerically similar, but nonsignificant, increases in the intermediate part of the medial hyperstriatum ventrale and lobus parolfactorius. There were no such increases in the right hemisphere of methyl anthranilate‐trained chicks or any region of either hemisphere of quinine‐trained chicks. Thus, the memory for methyl anthranilate is longer‐lasting than that for quinine and is associated with increased fucosylation in the left cerebral hemisphere and although in the short‐term, chicks can retain a memory of the one‐trial passive avoidance task with quinine as the aversant, this does not result in a localized increase in cerebral [3H]fucose incorporation.
Descending Projections from the Substantia Nigra and Retrorubral Field to the Medullary and Pontomedullary Reticular Formation
Authors: Von Krosigk M. , Smith A. D.
Published: April 2006

We have investigated the projection from the substantia nigra to the pontomedullary reticular formation in the rat using both retrograde and anterograde neuroanatomical tracers. Injections of a conjugate of wheatgerm agglutinin with horseradish peroxidase into the medullary or pontomedullary reticular formation resulted in the retrograde labelling of a continuous band of cells extending from the caudal half of the dorsolateral substantia nigra into the retrorubral field. Injections of the anterograde tracer Phaseolus vulgaris leukoagglutinin (PHA‐L) into either the dorsolateral substantia nigra or the caudally adjacent retrorubral field revealed a descending projection to the lateral medullary and pontomedullary brainstem, which terminated mainly within the lateral (parvicellular) reticular formation. The anterograde PHA‐L fibre labelling ran throughout the rostrocaudal extent of the parvicellular reticular formation and extended into the caudally continuous region, the medullary dorsal and medullary ventral reticular formation, where it tapered off. Also labelled, although more lightly, were the rostral and ventrolateral regions of the nucleus of the solitary tract and the magnocellular reticular formation. Electron microscopy established that the PHA‐L‐labelled fibres formed synaptic contacts with nerve cell bodies and dendrites in the parvicellular reticular formation. It is suggested that one role of this nigroreticular pathway might be to connect the basal ganglia with brainstem premotor neurons that influence orofacial musculature.
C‐fibre Function During the 6 Weeks Following Brief Application of Capsaicin to a Cutaneous Nerve in the Rat
Authors: Pini Adrian , Lynn Bruce
Published: April 2006

The functional properties of afferent fibres, especially C‐fibres, have been studied over the 46 days following application of capsaicinoids to a segment of the saphenous nerve in the rat. After 1–3 days, approximately half of the C‐afferents were found to be non‐conducting at or immediately distal to the treatment site. By 6–9 days there was some recovery of conduction at the treatment site, but few of the conducting fibres were excitable from the skin. From 12 days onwards, C‐fibre conduction in the segment of nerve both proximal and distal to the treatment site was reduced and of the conducting fibres relatively few had cutaneous receptive fields. In the sample of C‐fibres with cutaneous receptive fields the proportion of polymodal nociceptors was reduced markedly compared with control values. Analysis of the numbers of surviving units shows a large effect on C‐polymodal nociceptors, but no significant change in the numbers of any other type of afferent unit. At 2 weeks, when C‐fibre numbers were reduced to about one third, there was a virtual abolition of antidromic vasodilatation and an 85% fall in skin substance P levels. The synthetic capsaicinoid, NE‐21610, had similar actions to capsaicin and was more potent in depleting skin substance P levels. These results confirm that capsaicinoids produce a selective local lesion on nociceptive C‐fibres in rat cutaneous nerves. In addition, the transient and partial nature of functional recovery indicates that capsaicin may also cause a longer‐term toxic action that inhibits significant regeneration.
Host Brain Regulation of Fetal Locus Coeruleus Neurons Grafted to the Hippocampus in 6‐Hydroxydopamine‐Treated Rats. An Intracerebral Microdialysis Study
Authors: Kalén Peter , Cenci M. Angela , Lindvall Olle , Björklund Anders
Published: April 2006

Release properties of intrahippocampal transplants of noradrenergic neurons were monitored by microdialysis in awake and halothane‐anaesthetized rats. Fetal locus coeruleus neurons were implanted as a cell suspension into hippocampi deprived of their innate noradrenalin (NA) innervation by intraventricular 6‐hydroxydopamine treatment. Dialysis probes of the loop type were implanted into the dorsal hippocampus 1 ‐2 days before each experiment, i.e. 7–11 months after grafting. Age‐matched intact and lesion‐only animals served as controls. Microscopic analysis showed a graft‐derived tyrosine hydroxylase immunoreactive, presumably noradrenergic, fibre network throughout the dorsal hippocampal formation, surrounding the probe site. The innervation density varied from sub‐ to supranormal. The grafts restored baseline NA release in the graft‐reinnervated hippocampus to near‐normal levels both in awake and halothane‐anaesthetized animals. Potassium chloride (100 mM) in the perfusion fluid induced a dramatic increase in NA release that was similar in magnitude in the grafted and intact hippocampi. A NA uptake blocker (desipramine) added to the perfusion fluid at 5 μM induced a similar increase in NA output in the grafted and intact hippocampi, and the output was substantially reduced by tetrodotoxin, added at 1 μM in the presence of uptake blockade. Electrical stimulation of the lateral habenular nucleus (15 Hz, 0.5 mA) in halothane‐anaesthetized rats induced a significant increase in NA output both in the intact and grafted hippocampi. This effect was abolished by transection of the fasciculus retroflexus, which carries the efferent projections of the habenular complex. Behavioural activation through handling induced a consistent increase in NA release only in the intact animals, but in a few grafted rats (which also responded to habenular stimulation) the NA output was clearly elevated by handling. Forced immobilization induced a significant increase in NA output both in the intact and grafted hippocampi, but in the grafted ones the response was somewhat smaller and more transient. In the same set of animals, swimming in warm water (25–30°C) induced a sharp increase in NA output in the intact animals, whereas only one of the grafted rats responded by increased NA output. The results indicate that the locus coeruleus grafts, despite their ectopic location, can become functionally integrated with the host brain, and that the activity of the transplanted noradrenergic neurons can, under some circumstances, be modulated from the host brain in response to environmental challenges.
Specificity in the Development of Vertical Connections in Cat Striate Cortex
Authors: Katz Lawrence C.
Published: April 2006

The main efferent axons of pyramidal cells in layer 2/3 in the adult cat striate cortex make collateral connections specifically within layer 2/3 and layer 5 and avoid the intervening layer 4. Intracellular dye injections in vitro were used to determine how, during early postnatal development, this precise pattern of laminar connections was achieved. These investigations revealed that the pattern of collateral outgrowth was specific from the very earliest time that axons began sprouting collaterals. During the first postnatal week, sprouts were seen exclusively within layers 2/3 and 5; no evidence for a transient connection to layer 4 was observed. Furthermore, collaterals emerged simultaneously within layers 2/3 and 5, despite the large difference in the postmigratory ages of the two layers. By the end of the second postnatal week, the adult number of collaterals was achieved. Further elaboration of the local arbors occurred by repeated branching of already existing collaterals, rather than by addition of new collaterals to the main axon. These results demonstrate that the formation of local connections between cortical layers is highly specific, in contrast to the development of clustered horizontal connections by these same cells within layers 2/3 and 5, which involves extensive remodelling of local connections.
Cat Distal Forelimb Joints and Locomotion: An X‐ray Study
Authors: Caliebe F. , Häußler J. , Hoffmann P. , Illert M. , Schirrmacher J. , Wiedemann E.
Published: April 2006

The complex construction of the joint apparatus of the cat distal forelimb, which allows the paw three degrees of freedom, poses special requirements on the neural signals controlling the paw position. To understand the electromyography (emg) signals of the distal forelimb muscles during locomotion, it is necessary to know the kinematics of the forelimb joints in detail. As no such information is available, we used the pulsed X‐ray technique in trained cats during treadmill locomotion to analyse the angular excursions of the wrist, the metacarpophalangeal (MCP) and the proximal interphalangeal (PIP) joints. X‐ray illuminations were done in either the parasagittal or the frontal plane. At the beginning of the stance phase the wrist (WR) and the MCP joints extended slowly, and the PIP joints flexed. Whereas the WR and the PIP joints maintained a constant angular position of ∼200° and 60°, respectively, throughout the stance phase, extension continued in the MCP joints from 240° at touch‐down to 300° at the end of the stance phase. Slightly before lift‐off (100 ms) the WR and the MCP joints flexed rapidly. This flexion changed ∼150 ms after lift‐off into a slow extension. The PIP joints extended rapidly at the beginning and at the end of the swing phase, during the interposed period of the swing phase they displayed a slow flexion. Rotatory movements of the forelimb in the radioulnar joints were present during the swing and stance phases. During the swing phase the limb first supinated (starting 100 ms after lift‐off); pronation occurred immediately before ground contact. During the stance phase the supination angle was kept constant until 100 ms before lift‐off, when a short pronation was found. The paw was kept in an ulnar deviated position throughout the complete step cycle. Ulnar deviation decreased at the end of the swing and stance phases. The results of this study increase our understanding of how the body weight is transmitted on to the ground. They suggest four main functions for the skeletomotor apparatus and the underlying neural commands to secure the forward movement of the animal during the stance phase: (i) preparation and stabilization of a force‐transmitting platform; (ii) stabilization of the wrist and the carpal/metacarpal joints; (iii) stabilization of the supination angle; (iv) antigravity control of the extension in the MCP.
NMDA‐Receptor Antagonist Prevents Measles Virus‐induced Neurodegeneration
Authors: Andersson Tommy , Schultzberg Marianne , Schwarcz Robert , Löve Arthur , Wickman Charlotte , Kristensson Krister
Published: April 2006

N‐methyl‐d‐aspartate (NMDA) receptors represent a major subtype of excitatory amino acid receptors in the mammalian brain. In addition to their physiological role, NMDA receptors have been linked to the occurrence of nerve cell death in several neurodegenerataive diseases. The hamster neurotropic (HNT) strain of measles virus causes non‐inflammatory encephalopathy in mice. This is associated with neuronal loss in areas CA1 and CA3 of the hippocampus. Systemic treatment with the non‐competitive NMDA receptor antagonist 5‐methyl‐10,11‐dihydro‐5H‐dibenzo(a,d)cyclo‐hepten‐5,10‐imine maleate (MK‐801) prevented this cellular necrosis. Thus, a virus may have indirect neurodegenerative effects in the brain due to activation of NMDA receptors.
Glutamate‐like Immunoreactivity in the Pigeon Optic Tectum and Effects of Retinal Ablation
Authors: Morino Patrizia , Bahro Marcel , Cuénod Michel , Streit Peter
Published: April 2006

The pattern of glutamate‐like immunoreactivity was investigated in the pigeon optic tectum. The most impressive aspect of the labelling pattern was an accumulation of immunoreactive terminal‐like elements restricted to those superficial tectal layers that correspond to the termination zone of the retinal afferents. These immunoreactive puncta occurred frequently in small clusters. At the level of electron microscopy, many of the labelled nerve endings showed the characteristics of retinal terminals. Moreover, following unilateral retinal ablation a drastic loss of immunoreactive terminal‐like puncta was observed in the retinorecipient layers of the tectum contralateral to the lesion. The remaining glutamate‐immunoreactive terminal‐like elements had the light and electron microscopic features typical of the afferents from the nucleus isthmi, pars parvocellularis (lpc). The relation between the latter result and the transmitter specificity of the afferents from this subtectal nucleus is unclear at present. On the other hand, the light and electron microscopic labelling patterns and the effect of retinal ablation suggest that afferents from retina and from lpc are the only major sources for glutamate‐immunoreactive terminals in the pigeon optic tectum. Furthermore, the results are well in line with previous data indicating glutamate as neurotransmitter at least in part of the retinal afferents to the pigeon optic tectum.
Inactivation of Delayed Potassium Current in Cultured Bovine Chromaffin Cells
Authors: Sala Salvador , Soria Bernat
Published: April 2006

Potassium currents of cultured bovine chromaffin cells in the presence of CdCl2 (0.5 mM) or CoCl2 (2–4 mM) may be described as a component that follows an n4 kinetics over the first 100 ms. However, during prolonged voltage clamp steps (5–20 s) this current reaches a peak and then declines to a non‐zero steady‐state level. In the absence of potassium accumulation, slow decay has been attributed to slow inactivation of the K+ conductance. Slow inactivation of calcium‐independent potassium currents responds to the following: (i) the inactivation has a time course that may be fitted by a sum of two exponentials; (ii) inactivation is use‐dependent (increasing frequency or duration of depolarizing pulses increases the extent of inactivation). Use‐dependent inactivation does not appear when short (100 ms) hyperpolarizing prepulses are applied; (iii) at a membrane potential of −60 mV, approximately 20% of the channels are inactivated; (iv) recovery from inactivation is very slow. At a holding potential of −70 mV it takes about 20 s to reach the original value. The rate of inactivation recovery is voltage‐dependent. The more hyperpolarized the membrane potential, the faster the recovery. The presence of use‐dependent inactivation with slow recovery could be relevant for the stimulus–secretion coupling modulation in chromaffin cells.
Spatial and Temporal Patterns of Neurogenesis in the Chick Retina
Authors: Prada Carmen , Puga José , Pérez‐Méndez Luisa , López Rosario , Ramírez Galo
Published: April 2006

Chick embryo retinas were labelled in ovo by single injections of [3H]thymidine at selected times between days 2 and 12 of incubation. Embryos were later removed, at different stages of development, and the retinas processed for autoradiography of either serial sections or dissociated cell preparations. Analysis of unlabelled cells shows that neurogenesis starts, on day 2 of incubation, in a dorsotemporal area of the central retina, close to the posterior pole and to the optic nerve head. A gradient of neurogenesis spreads from this central area to the periphery, where neurogenesis ends, shortly after day 12, when the last few bipolar cells withdraw from the cell cycle. Additional dorsal‐to‐ventral and temporal‐to‐nasal gradients can be discerned in our autoradiographs. In all retinal sectors, ganglion cells start first to withdraw from the cell cycle, followed, with substantial overlapping, by amacrine, horizontal, photoreceptor plus Müller, and bipolar neuroblasts. Ganglion cells are also the first to reach the 50% level of unlabelled cells, followed this time by horizontal, photoreceptor, amacrine, Müller and bipolar cells. Finally, 100% levels of unlabelled cell populations are attained simultaneously by ganglion, horizontal and photoreceptor cells, followed by amacrine, then by Müller, and last by bipolar cells. Although all classes of neurons, in varying proportions, are being produced most of the time, our results also demonstrate that, in any given retinal area, the first cells leaving the cycle are determined to become ganglion cells, and the last ones bipolar cells, and not other types.
Calcitonin Gene‐related Peptide Stimulates the Induction of c‐fos Gene Expression in Rat Astrocyte Cultures
Authors: Haas Carola A. , Reddington Martin , Kreutzberg Georg W.
Published: April 2006

The action of calcitonin gene‐related pepide (CGRP) was studied on c‐fos gene expression in rat astrocyte cultures. A strong and transient increase in c‐fos mRNA was observed in cultured astrocytes after treatment with CGRP. Quantitative Northern blot analysis revealed an increase of c‐fos mRNA within 15 min, a peak after 30 min with a 10–15 fold increase over unstimulated cells and a subsequent decline. Induction of the c‐fos gene by CGRP was concentration‐dependent, half maximal stimulation of c‐fos mRNA being obtained with 100 nM CGRP. The CGRP effect appeared to be mediated by a CGRP receptor and calcitonin was found to mimic only weakly the action of CGRP on cultured astrocytes. Calcitonin transiently induced c‐fos gene expression with a similar time course to CGRP, but its effect was much less pronounced. Agents affecting the intracellular cyclic AMP level, forskolin and Ro 20–1724, stimulated c‐fos mRNA in a strong and transient fashion with a temporal sequence similar to the response to CGRP. Further, the phosphodiesterase inhibitor Ro 20–1724 potentiated the action of CGRP on c‐fos mRNA induction, suggesting a role for cyclic AMP in the action of CGRP. The present results indicate that CGRP may play a physiological role as a regulator of astrocyte gene expression.
AMPA Neurotoxicity in Rat Cerebellar and Hippocampal Slices: Histological Evidence for Three Mechanisms
Authors: Garthwaite Giti , Garthwaite John
Published: April 2006

Excitatory amino acid‐induced death of central neurons may be mediated by at least two receptor types, the so‐called NMDA (N‐methyl‐d‐aspartate) and AMPA (α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazoleproprionate) receptors. We have studied the neurodegenerative mechanisms set in motion by AMPA receptor activation using incubated slices of 8‐day‐old rat cerebellum and hippocampus. In both preparations, AMPA induced a pattern of degeneration that differed markedly from the one previously shown to be elicited by NMDA. In cerebellar slices, AMPA induced the degeneration of most Purkinje cells together with a population of Golgi cells; in hippocampal slices the neurons were affected in the order CA3 > CA1 > dentate granule cells. Three mechanisms could be discerned: an acute one in which neurons (e.g. cerebellar Golgi cells) underwent a rapid degeneration; a delayed one in which the neurons (Purkinje cells and hippocampal neurons) appeared to be only mildly affected immediately after a 30 min exposure but then underwent a protracted degeneration during the postincubation period (1.5–3 h); and finally a slow toxicity, which took place during long (2 h) exposures to AMPA (3–30 μM). Although Purkinje cells were vulnerable in both cases, the efficacy of AMPA was higher for the delayed mechanism than for the slow one. The pathology displayed by the acutely destroyed Golgi neurons was a classical oedematous necrosis, whereas most neurons vulnerable to the delayed and slow mechanisms displayed a ‘dark cell degeneration’, whose cytological features bore a close resemblance to those of neurons irreversibly damaged by ischaemia, hypoglycaemia or status epilepticus in vivo.
Expression of Human Neurofilament‐light Transgene in Mouse Neurons Transplanted into the Brain of Adult Rats
Authors: Vidal‐Sanz Manuel , Villegas‐Pérez Maria P. , Carter David A. , Julien Jean‐Pierre , Peterson Alan , Aguayo Albert J.
Published: April 2006

To investigate the expression of nerve cell‐specific transgene products in neural transplants, we implanted into the hippocampus of immunosuppressed adult Sprague – Dawley rats cell suspensions obtained from the septal region of the fetal brain of mice that carry the human neurofilament‐light (hNF‐L) gene. In grafts examined between 3 weeks and 7 months after transplantation, axons and nerve cell somata immunoreacted to antibodies specific to the human NF‐L subunit. Thus, the hNF‐L protein appears to be a suitable marker of these grafted neurons. Transgenic mice bearing the hNF‐L gene may be a convenient source of donor tissue or be used as hosts for neural transplantation studies. Furthermore, the hNF‐L promoter/enhancer elements in this transgene may help direct neuronal expression of heterologous genes that could influence nerve cell responses in either the transplant or host tissues.
Pharmacological and Electrophysiological Properties of Recombinant GABAA Receptors Comprising the α3, β1 and γ2 Subunits
Authors: Knoflach F. , Backus K. H. , Giller T. , Malherbe P. , Pflimlin P. , Möhler H. , Trube G.
Published: April 2006

To assess the role of subunits for channel function and drug modulation in recombinant GABAA receptors, the α3β1γ2 subunits and the dual combinations α3β1, β1γ2 and α3γ2 were expressed by transfection of human embryonic kidney cells and by RNA injection in Xenopus oocytes (α3β1γ2 combination). GABA‐induced chloride currents were recorded using the whole‐cell configuration of the patch‐clamp technique (transfected cells) or the voltage‐clamp technique (oocytes). The currents recorded from the α3β1Γ2 subunit combination in transfected cells were reduced by bicuculline and picrotoxin, enhanced by flunitrazepam in a flumazenil‐sensitive manner and reduced by β‐carboline‐3‐carboxylic acid methyl ester (β‐CCM). The GABA‐induced current was reduced by β‐CCM in all combinations containing the γ2 subunit, but potentiation by flunitrazepam was only obtained when the 72 subunit was coexpressed in the presence of the α3 subunit (α3β1γ2 or α3γ2). The GABA sensitivities of the receptors were similar when the α3β1γ2 combination was expressed in oocytes (half‐maximum effective concentration = 240 μM) or in the kidney cell line (270 μM). However, the currents were less potentiated by flunitrazepam in oocytes (129% of controls) than in transfected cells (189%). These results suggest that the α3β1γ2 subunit combination, which is coexpressed in various brain regions as shown by in situ hybridization histochemistry, may represent a building block of functional GABAA receptors in situ.
The Critical Period for Experience‐dependent Plasticity in a System of Binocular Visual Connections in Xenopus laevis: Its Extension by Dark‐rearing
Authors: Grant S. , Dawes E. A. , Keating M. J.
Published: April 2006

Following surgical rotation of an eye, the Xenopus‘intertectal’ system is capable of a vision‐dependent alteration of its connectivity, that restores spatial registration of binocular maps on the optic tectum. In the preceding paper (Keating and Grant, Eur. J. Neurosci., 4, 27–36, 1992), we reported that this capacity undergoes a progressive, age‐dependent restriction during a critical period around the time of metamorphosis, so that rotations produced in animals aged 3 months postmetamorphosis normally evoke no such alteration of the system. Here we examine whether this restriction is rigidly age‐dependent or whether vision can influence its profile. We report that in animals dark‐reared from embryonic stage 35 through the critical period to 3 months, 1 year or even 2 years after metamorphosis, rotations instituted at those ages now result in intertectal reorganization if a period of normal vision is allowed after the operation. Similarly, intertectal alteration was also seen in animals eye‐rotated at larval stage 58, then dark‐reared just for the duration of the critical period, and subsequently returned, at 3 months of age, to a normal visual environment. We conclude, therefore, that the normal developmental restriction in the plasticity of the Xenopus intertectal system is not strictly age‐dependent, but that vision contributes to the process by activating the underlying plasticity mechanisms.
Calbindin‐D28K (CaBP28k)‐like Immunoreactivity in Ascending Projections
Authors: Menètrey D. , de Pommery J. , Baimbridge K. G. , Thomasset M.
Published: April 2006

This study concerns the involvement of calbindin‐D28K (CaBP28k)‐containing neurons in the efferent projections of both the trigeminal nucleus caudalis and the dorsal vagal complex (nucleus of the solitary tract and area postrema) in rats. Recent evidence has shown that these projections are particularly important for the processing of visceroception and/or nociception at central levels. The trigeminal nucleus caudalis has dense projections to both the nucleus of the solitary tract and the parabrachial area; the dorsal vagal complex is intimately connected to the parabrachial area. CaBP28k is a calcium‐binding protein the function of which could be a determining factor in controlling the excitability of cells by acting on intrinsic calcium metabolism. CaBP28k content of projections was ascertained using a double labelling approach that combined the retrograde transport of a protein ‐ gold complex to identify projection cells and immunocytochemistry to identify CaBP28k‐positive cells. The trigeminal nucleus caudalis is rich in both CaBP28k‐immunoreactive cells and cells projecting to the parabrachial area or the nucleus of the solitary tract. Cells containing both the protein and the retrograde tracer, however, were mostly restricted to the superficial layers (laminae I and outer II) and to their rostral extensions, the dorsal paramarginal and paratrigeminal nuclei. These trigeminal subdivisions are targets for nociceptive, visceroceptive and thermal inputs of peripheral origins. The dorsal vagal complex is rich in CaBP28k. Dense populations of immunoreactive cells are observed in the ventrolateral part of the area postrema and all of the three main subdivisions of the nucleus of the solitary tract (rostral gustatory, ventrolateral respiratory and medial cardiovascular subregions). The subnucleus commissuralis, subnucleus centralis and dorsal subnuclei are particularly densely stained. The subnucleus centralis, which is involved in regulating food and water intake, does not project to the parabrachial area. The area postrema, subnucleus commissuralis and dorsal subnuclei, which are implicated in cardiovascular and/or ingestive behaviours, have dense projections to the parabrachial area, many of which contain CaBP28k. The present results demonstrate that CaBP28k‐containing cells form a major part of the solitary and trigeminal projection systems, including subregions that are involved in visceroception and/or nociception processing. The location of solitary nucleus projection cells overlaps those of some neuropeptidergic projecting populations, suggesting colocalization. Consequently, certain neuropeptidergic actions may be CaBP28k‐dependent.
Calbindin‐D28K (CaBP28k)‐like Immunoreactivity in Ascending Projections
Authors: Menétrey D. , de Pommery J. , Thomasset M. , Baimbridge K. G.
Published: April 2006

This study concerns the involvement of calbindin‐D28K (CaBP28k)‐containing neurons in ascending spinal projections to the brainstem (nucleus of the solitary tract, lateral reticular nucleus area), pontine (parabrachial area) and mesencephalic (periaqueductal grey) structures. All these central structures are important in the processing of visceroception and visceronociception and all are targets for spinal efferents from similar areas. CaBP28k controls the excitability of cells by acting on intrinsic calcium metabolism. Results refer to the caudal spinal areas where the visceroceptive regions are concentrated. Experiments were performed through a double labelling approach that combined the retrograde transport of a protein ‐ gold complex to identify the projection cells and immunohistochemistry to identify the CaBP28k‐positive cells. The caudal spinal cord is rich in both CaBP28k‐containing and projection cells. Cells colocalizing the protein and the retrograde tracer were quite numerous, with a particularly high concentration in the superficial layers of the dorsal horn (laminae I and outer II) and the lateral spinal nucleus. The other spinal areas containing immunoreactive projection cells were the reticular part of the neck of the dorsal horn, the medial laminae VII and VIII, lamina X and the sacral parasympathetic nucleus. The superficial layers and the neck of the dorsal horn are targets for nociceptive, visceroceptive and thermal inputs; the sacral parasympathetic column and lamina X are involved in visceroceptive integration. A functional role for the lateral spinal nucleus has not yet been established. Quite similar results were obtained for each of the ascending pathways under study. The high incidence of CaBP28k in spinal pathways suggests that calbindin has a major role in controlling the excitability of spinal cells subserving the processing of visceroception and/or visceronociception information to supraspinal levels. The participation of CaBP28k‐immunoreactive cells in spinal ascending tract cells largely outnumbers those previously reported for various neuropeptides (Leah et al., Neuroscience, 24, 195–207, 1988)