bluuebunny/crossref_metadata_2025 huggingface dataset:
Immediate Early Gene Expression in the Rat Forebrain Following Striatal Infusion of Quinolinic Acid
Authors: Purkiss R. J. , Legg M. D. , Hunt S. P. , Davies S. W.
Published: April 2006

Expression in the rat forebrain of immediate early genes belonging to the fos and jun families was investigated at various time points following an intrastriatal infusion of quinolinic acid. Fos immunoreactivity was rapidly and transiently induced, exhibiting maximal intensity 2 h post‐lesion, and was principally located in neuronal nuclei situated around the periphery of the lesioned striatum, in regions that subsequently show little, if any, neurodegeneration. Fos immunoreactivity was additionally expressed throughout the ipsilateral cortex. In contrast, Jun immunoreactivity, which remained undetectable for 12 h after the lesion, reached its maximal intensity 24 h post‐lesion, at which time it was most densely distributed in neuronal nuclei found within the central lesioned areas of the striatum. In situ hybridization analysis using radiolabeled oligonucleotide probes confirmed this spatial and temporal separation between c‐fos and c‐jun expression within the striatum and extended it further, showing that, whilst jun mRNA displayed very similar expression characteristics to those of c‐fos mRNA, both fos B mRNA and jun D mRNA exhibited induction patterns closely resembling those of c‐jun mRNA. These results clearly suggest that two distinct programmes of immediate early gene expression can be induced in vivo. The rapid (2 h) and transient induction of c‐fos/jun B may well be a response to NMDA receptor activation, whereas the molecular signal for the late (24 h) and sustained induction of c‐jun/ fos B/jun D is currently a focus for our investigations.
Expression of GAP‐43 mRNA in Mouse Spinal Cord Following Unilateral Peripheral Nerve Damage: is There a Contralateral Effect?
Authors: Booth C. M. , Brown M. C.
Published: April 2006

Two new oligonucleotide anti‐sense probes and their corresponding sense probes specific for mouse GAP‐43 mRNA were synthesized and end‐labelled with digoxygenin. They were used to localize GAP‐43 mRNA in the spinal cords of normal mice and in mice 3 and 7 days following unilateral sciatic nerve cut. GAP‐43 mRNA was found to be expressed at low levels in motor and other neurons of the normal spinal cords. As expected from other studies, up‐regulation occurred in the cell bodies of axotomized motor neurons but, in addition, up‐regulation was also observed in the cell bodies of intact motor neurons contralateral to the lesion. Densitometer measurements showed that the up‐regulation of GAP‐43 mRNA was less in the intact, contralateral motor neuron cell bodies than in the axotomized motor neuron cell bodies and furthermore was transient, being higher at 3 days than at 7 days following axotomy. Both anti‐sense probes gave the same result, although differences in cellular localization were observed, and the two sense probes were negative. Probe binding was abolished by pretreatment of the sections with ribonuclease and hybridization was carried out under different conditions of stringency in order to ascertain whether the contralateral expression of GAP‐43 mRNA was a true reflection of its distribution in vivo. There is conflicting evidence on the presence or absence of contralateral effects following unilateral peripheral nerve injury in the literature, and it is suggested that these differences can be accounted for by the methodology and type of probe used.
Non‐quantal Release of Acetylcholine Affects Polyneuronal Innervation on Developing Rat Muscle Fibres
Authors: Vyskočil F. , Vrbová G.
Published: April 2006

The membrane potential at endplates of the rat hemidiaphragm for 9‐day‐old rats increases by 1.8 mV after addition of D‐tubocurarine. The endplate depolarization before the addition of D‐tubocurarine is considered to be due to non‐quantal release (NQR) of acetylcholine (ACh). In the presence of an anticholinesterase this depolarization increased. It was further enhanced by 0.1 ‐1.0 mM Mg2+ and reduced by 4 mM Mg2+ concentration. Thus the regulation of NQR at neuromuscular junctions of developing rat muscles is similar to that seen in adult mammalian species. The effect of NQR of ACh on neuromuscular contacts of muscle fibres from 8–9‐day‐old rat diaphragm and soleus muscles was studied. Pre‐incubating the muscles in solutions where NQR was increased by lowering Mg2+ caused a significant (P < 0.01) reduction of neuromuscular contacts. This reduction did not occur when muscles were incubated in high Mg2+, when NQR is reduced. Increasing quantal release by high Ca2+ also caused a reduction of neuromuscular contacts. Histological examination of soleus muscle fibres treated with an anticholinesterase showed that muscles incubated in solutions with low (0.1 mM) concentrations of Mg2+ had significantly fewer neuromuscular contacts (38%) than those incubated in high concentrations of Mg2+ (61%). It is concluded that the NQR as assessed here contributes to the elimination of polyneuronal innervation during postnatal development of rat muscles.
Effects of Visual Cortex Lesions on Orientation Discrimination of Illusory Contours in the Cat
Authors: De Weerd Peter , Sprague James M. , Raiguel Steven , Vandenbussche Erik , Orban Guy A.
Published: April 2006

We have trained five cats in orientation discrimination using different contours, and compared the deficits caused by lesions of cortical areas 17 and 18 (tier I) to the deficits induced by removal of those areas receiving afferents originating in areas 17 and 18 (tier II). As contour stimuli we used two types of illusory contours and a luminance bar. The two illusory contours were defined by opposed line‐ends. One of them coincided with a luminance gradient whereas the other did not. Tier I lesions destroyed the capacity to discriminate the orientation of both illusory contours, and also caused an important, though less severe, deficit in bar orientation discrimination. The deficits induced by tier I lesions were permanent. Tier II lesions also caused significant deficits in orientation discrimination of illusory contours, but only a negligible deficit in bar orientation discrimination, and this result was not a mere consequence of a difference in difficulty between the tasks involving bars and illusory contours. In addition, tier II lesions differentiated between illusory contour types, the deficit being more pronounced for the illusory contour without luminance gradient than for the one with luminance gradient. In contrast to tier I lesions, tier II lesions allowed significant recovery, leading to small final deficits for all contour types tested.
Complete Axon Arborization of a Single CA3 Pyramidal Cell in the Rat Hippocampus, and its Relationship With Postsynaptic Parvalbumin‐containing Interneurons
Authors: Sik A. , Tamamaki N. , Freund T. F.
Published: April 2006

The complete axon arborization of a single CA3 pyramidal cell has been reconstructed from 32 (60 /μm thick) sections from the rat hippocampus following in vivo intracellular injection of neurobiotin. The same sections were double‐immunostained for parvalbumin‐a calcium‐binding protein selectively present in two types of GABAergic interneurons, the basket and chandelier cells‐in order to map boutons of the pyramidal cell in contact with dendrites and somata of these specific subsets of interneurons visualized in a Golgi‐like manner. The axon of the pyramidal cell formed 15 295 boutons, 63.8% of which were in stratum oriens, 15.4% in stratum pyramidale and 20.8% in stratum radiatum. Only 2.1% of the axon terminals contacted parvalbumin‐positive neurons. Most of these were single contacts (84.7%), but double or triple contacts (15.3%) were also found. The majority of the boutons terminated on dendrites (84.1%) of parvalbumin‐positive cells, less frequently on cell bodies (15.9%). In order to estimate the proportion of contacts representing synapses, 16 light microscopically identified contacts between boutons of the filled pyramidal cell axon and the parvalbumin‐positive targets were examined by correlated electron microscopy. Thirteen of them were found to be asymmetrical synapses, and in the remaining three cases synapses between the labelled profiles could not be confirmed. We conclude that the physiologically effective excitatory connections between single pyramidal cells and postsynaptic inhibitory neurons are mediated by a small number of contacts, mostly by a single synapse. This results in a high degree of convergence and divergence in hippocampal networks.
Long Fibre Growth by Axons of Embryonic Mouse Hippocampal Neurons Microtransplanted into the Adult Rat Fimbria
Authors: Davies S. J. A. , Field P. M. , Raisman G.
Published: April 2006

We have described a method for the microtransplantation of a suspension of a few thousand cells from mid to late embryonic mouse hippocampi into the fimbria of immunosuppressed adult rat hosts. There was close graft‐to‐host contact, across a non‐scarred interface. The transplanted cells included CA3 type pyramids, and were enclosed within the host myelinated fibre tract, whose glial framework was largely undisturbed. Immunohistochemistry of two species‐specific markers (M6 and Thy‐1.2) showed that the donor mouse neurons grew fine (<0.5 μm diameter) axons which extended singly or in fascicles through the rat host fimbria for a maximum distance of at least 10 mm. The donor axons were intimately integrated among and closely aligned to the host tract axons and to the interfascicular glial rows of the host tract. The axons travelled (i) laterally through the ipsilateral fimbria, (ii) medially across the midline in the ventral hippocampal commissure to reach the contralateral fimbria and alveus, and (iii) rostro‐medially to the septum. On approaching the terminal fields appropriate to hippocampal CA3 pyramidal cell axons, the transplant axons gave rise to fine preterminal branches which were continuous with a reticular or amorphous immunoreactivity in the stratum oriens and stratum pyramidale of the ipsilateral hippocampus, and in the lateral and triangular septal nuclei. The donor axons extended along the host fimbria at a rate of ∼ 1 mm per day, reaching their terminal field destinations by ∼1–2 weeks. At 7 weeks the projections were maintained, but with little further extension. These observations indicate that the microenvironment of myelinated adult fibre tracts is permissive for an abundant and rapid growth of axons from transplanted embryonic cell suspensions. These axons can leave host tracts to invade appropriate terminal fields.
Synaptic Plasticity in an In Vitro Slice Preparation of the Rat Nucleus Accumbens
Authors: Pennartz C. M. A. , Ameerun R. F. , Groenewegen H. J. , Lopes da Silva F. H.
Published: April 2006

Extra‐ and intracellular recordings in slices were used to examine what types of synaptic plasticity can be found in the core of the nucleus accumbens, and how these forms of plasticity may be modulated by dopamine. Stimulus electrodes were placed at the rostral border of the nucleus accumbens in order to excite primarily infralimbic and prelimbic afferents, as was confirmed by injections of the retrograde tracer fluoro‐gold. In extracellular recordings, tetanization induced long‐term potentiation (LTP) of the population spike in 20 out of 53 slices. The presynaptic compound action potential did not change following LTP induction. For the intracellularly recorded excitatory postsynaptic potential, three types of synaptic plasticity were noted: long‐term potentiation (16 out of 54 cells), decremental potentiation (eight cells) and long‐term depression (LTD; six cells). No correlation was found between the occurrence of potentiation or depression and various parameters of the tetanic depolarization (e.g. peak voltage, integral under the curve). The N‐methyl‐d‐aspartate receptor antagonist d(–)‐2‐amino‐5‐phosphonopentanoic acid (50 μM; d‐AP5) reduced, but did not completely prevent, the induction of LTP. The incidence of LTD was not markedly affected by d‐AP5. No difference in LTP was found when comparing slices bathed in dopamine (10 μM) and controls. Likewise, slices treated with a mixture of the D1 receptor antagonist Sch 23390 (1 μM) and the D2 antagonist S(–)‐sulpiride (1 μM) generated a similar amount of LTP as controls. In conclusion, both LTP and LTD can be induced in a key structure of the limbic‐innervated basal ganglia. LTP in the nucleus accumbens strongly depends on N‐methyl‐d‐aspartate receptor activity, but is not significantly affected by dopamine.
Intrastriatal Transplants of Embryonic Dopaminergic Neurons Counteract the Increase of Striatal Enkephalin Immunostaining but not Serotoninergic Sprouting Elicited by a Neonatal Lesion of the Nigrostriatal Dopaminergic Pathway
Authors: Abrous D. N. , Manier M. , Mennicken F. , Feuerstein C. , Moal M. Le , Herman J. P.
Published: April 2006

The aim of the our experiment was to compare the ability of intrastriatal implants of embryonic dopaminergic neurons to reverse two kinds of postlesion modification in the host brain: the change in the activity level of neurons in the denervated area and morphological modifications, e.g. collateral sprouting. The ascending dopaminergic system of 3‐day‐old rat pups was unilaterally lesioned by an intrahypothalamic injection of the neurotoxin 6‐hydroxydopamine. This lesion has been described previously to induce an increase in the level of activity of striatal enkephalinergic neurons. The same lesion leads also to sprouting of the serotoninergic afferents in the striatum, leading to hyperinnervation of this structure. The existence of these modifications thus offers the possibility of testing the influence of grafts in one structure of the same animal on two lesion‐induced reactions of different nature. A cell suspension obtained from mesencephali of embryonic day 14 rats and containing dopaminergic neurons was implanted into the denervated striatum of lesioned animals 5 days after the lesion. Nine months later the animals were killed and immunohistochemistry was performed on striatal sections using antibodies directed against tyrosine hydroxylase, methionine enkephalin and serotonin. Intensity of immunostaining (methionine enkephalin and serotonin) as well as innervation density (serotonin) was quantified through the use of a computer‐assisted image analyser. The lesion led to the disappearance of striatal dopaminergic innervation. Implanted dopaminergic neurons were found scattered in the striatum and restored a dopaminergic innervation in a large portion of this structure. There was a marked increase in striatal methionine enkephalin immunostaining in lesioned animals, which was most pronounced in the dorsolateral part of the striatum (+ 150% compared to control values), while in the ventral part it was slight or non‐existent. The density of striatal serotoninergic innervation was also increased by ∼250% relative to control values. In grafted animals striatal enkephalin immunostaining was similar to that observed in control animals. On the other hand, the serotoninergic hyperinnervation was still present in the graft‐bearing striata. These results suggest that while intrastriatal implants of embryonic dopaminergic neurons are able to counteract modifications in the functioning of local striatal neuronal systems such as the increase in enkephalinergic activity or receptor hypersensitivity occurring as a result of the lesion, they might be unable to reverse postlesion morphological modifications.
Mediation of Thalamic Sensory Responses In Vivo by ACPD‐activated Excitatory Amino Acid Receptors
Authors: Eaton S. A. , Birse E. F. , Wharton B. , Sunter D. C. , Udvarhelyi P. M. , Watkins J. C. , Salt T. E.
Published: April 2006

The existence of the so‐called metabotropic excitatory amino acid receptor has been known for some years. Various functions have been suggested for this receptor, but the lack of selective antagonists for (IS, 3R)‐aminocyclopentane dicarboxylic acid (ACPD) has precluded the direct demonstration of a functional role for this receptor in synaptic processes. We describe here a specific antagonism of the excitatory responses of thalamic neurons to ACPD by two novel antagonists, and a parallel antagonism by these compounds of sensory synaptic responses to noxious stimuli of the same neurons. This provides the first direct pharmacological evidence for a functional role of ACPD‐sensitive receptors in central neurotransmission, and indicates that these receptors may play an important part in central sensory processes.
Differential Expression of Immediate Early Genes in Rubrospinal Neurons Following Axotomy in Rat
Authors: Jenkins R. , Tetzlaff W. , Hunt S. P.
Published: April 2006

Many immediate early genes are rapidly and transiently expressed in the central nervous system following a variety of stimuli. Damage to the axons of peripheral and certain central neurons has been shown to result in a long‐term increase in expression of c‐Jun in the parent cell bodies. In the peripheral nervous system this increased expression of c‐Jun protein and mRNA develops over 24 h following sciatic nerve section and is maintained if the damaged nerve is ligated, but returns to basal levels if the peripheral nerve is allowed to regenerate. Here, we report on the response of rubrospinal neurons to spinal cord hemisection at levels C3 and T10. c‐Jun expression was first seen at 12 h post‐lesion in a limited number of rubral neurons. The number of positively stained neurons increased up to 10 days post‐lesion and then declined over the following weeks. By 7 weeks post‐lesion there was still evidence of c‐Jun immunoreactivity in both large and other clearly atrophic rubrospinal neurons. c‐Fos immunoreactivity was seen only at 12–48 h in a small number of rubrospinal neurons. Evidence from retrograde tracing experiments following fluorogold application to the hemisected cord suggested that all c‐Jun‐positive neurons projected into the spinal cord. No c‐Jun response was seen following a lesion at T10. These observations on the rubrospinal tract contrast with previous results of immediate early gene expression studies in neurons of the substantia nigra, pars compacta following axotomy with 6‐hydroxydopamine, where c‐Fos immunoreactivity was not seen and the increased expression of c‐Jun declined to basal levels within 21 days. These results suggest that the immediate early gene response of different central neuronal pathways to damage may vary. This may have important implications for any experimental intervention designed to facilitate the repair of damaged neuronal pathways in the adult brain.
Cytochemical Redistribution of 5′‐Nucleotidase in the Developing Cat Visual Cortex
Authors: Schoen S. W. , Kreutzberg G. W. , Singer W.
Published: April 2006

The adenosine‐producing ectoenzyme 5′‐nucleotidase has recently been shown to undergo a marked redistribution during development of the cat visual cortex and to be involved in the remodelling of ocular dominance columns (Schoen et al., J. Comp. Neurol., 296, 379 – 392, 1990). Using an enzyme‐cytochemical technique, we now investigate the developmental redistribution of 5′‐nucleotidase activity in area 17 of kittens at the ultrastructural level. Between postnatal days 35 and 42, when 5′‐nucleotidase is concentrated in layer IV, enzyme reaction product occupies the clefts of asymmetrical synapses within the neuropil. During later development (9th and 13th postnatal weeks), when 5′‐nucleotidase spreads over all cortical laminae, the enzyme disappears from its synaptic localization and becomes increasingly associated with astrocytic membranes. The transient appearance of 5′‐nucleotidase at synapses parallels the time‐course and laminar profile of the synaptic remodelling which takes place during the critical period of visual cortex development. This suggests that synapse‐bound 5′‐nucleotidase activity plays a role in synaptic malleability, whereas its later association with glial profiles is likely to reflect other functions of the enzyme.
Long‐term Effects of Selective Target Removal on Brainstem Premotor Neurons in the Adult Cat
Authors: de La Cruz Rosa R. , Pastor Angel M. , Delgado‐García José M.
Published: April 2006

The electrical activity of antidromically identified abducens internuclear neurons selectively deprived of their target motoneurons was recorded in chronic alert cats. Target motoneurons were killed by the injection of the cytotoxic lectin of Ricinus communis into the medial rectus muscle. Following target removal, the discharge pattern of abducens internuclear neurons showed an overall decrease in firing rate, a significant reduction in their sensitivity to eye position and velocity, and the presence of anomalous responses such as bursts of spikes associated with off‐directed saccades. The decreased excitability of abducens internuclear neurons correlated well with a marked reduction in the synaptic efficacy of their inputs. Thus, both excitatory and inhibitory synaptic potentials of vestibular origin showed a noticeable decrease in amplitude. The alterations in firing properties and synaptic transmission were only observed during an initial period of 3 weeks following ricin injection. Within 1 month the electrophysiological parameters returned to control values and remained unaltered for 1 year. Retrograde labelling of abducens internuclear neurons revealed that no cell death occurred after target loss. The anterograde axonal labelling of these neurons showed a progressive decrease in the density of their axonal terminals, and no sign of redistribution to other areas was found. These findings indicate that abducens internuclear neurons are not dependent on the presence of their natural target cells, either for the survival or for the maintenance of appropriate physiological signals.
Cholecystokinin in Mammalian Primary Sensory Neurons and Spinal Cord: In Situ Hybridization Studies in Rat and Monkey
Authors: Verge V. M. K. , Wiesenfeld‐Hallin Z. , Hökfelt T.
Published: April 2006

The peptide cholecystokinin (CCK) has been suggested to be involved in nociception, but its exact localization at the level of the spinal cord and in spinal ganglia has been a controversial issue. Therefore the distribution of messenger RNA (mRNA) for CCK was studied by in situ hybridization using oligonucleotide probes on sections of adult rat lumbar dorsal root ganglia following unilateral section of the sciatic nerve and on sections of untreated monkey trigeminal ganglia, spinal cord and spinal ganglia from all levels. For comparison, calcitonin gene‐related peptide (CGRP) mRNA was also studied in the monkey tissue using the same techniques. Peripheral sectioning of the sciatic nerve in the rat resulted in the appearance of detectable CCK mRNA in up to 30% of remaining ipsilateral L4 and L5 dorsal root ganglion neurons 3 weeks after surgery, with a distinct but more limited appearance also in the contralateral ganglia. No cells, or only single cells, could be seen in normal control rat ganglia. In contrast, in the normal monkey, ∼20% of dorsal root ganglion neurons, regardless of spinal level, and 10% of trigeminal ganglia neurons expressed mRNA for CCK. CGRP mRNA was expressed at detectable levels in ∼80% of these monkey dorsal root ganglion neurons. In the monkey spinal cord, CCK mRNA was detected in the dorsal horn and in motoneurons, whereas CGRP mRNA was only seen in motoneurons. The present results suggest that CCK peptides can be involved in sensory processing in the dorsal horn of the spinal cord in normal monkeys and in rats after peripheral nerve injury, adding one more possible excitatory peptide to the group of mediators in the dorsal horn.
The glia‐derived protease nexin 1 persists for over 1 year in rat brain areas selectively lesioned by transient global ischaemia
Authors: Nitsch C. , Scotti A. L. , Monard D. , Heim C. , Sontag K.‐H.
Published: April 2006

The re‐expression of the developmentally regulated serine protease inhibitor glia‐derived nexin (GDN) was investigated 1 year after transient global ischaemia induced by the four‐vessel occlusion technique in rats. The CA1 sector of the hippocampus was severely shrunken due to the absence of pyramidal cells, but still clearly discernible due to the continued presence of the parvalbumin‐containing GABAergic neurons. In this partially neuron‐depleted hippocampus, GDN immunoreactivity was found in reactive astrocytes containing glial fibrillary acidic protein. GDN‐positive astrocytes were also found in other lesioned areas, the reticular thalamic nucleus and the cerebellar cortex. Thus, the re‐expression of GDN in the adult excitotoxically lesioned brain described previously in the gerbil model of ischaemia persists. The continued presence of the protease inhibitor might disturb the proteolytic balance and lead to the deposition of pathological breakdown products of proteins, e.g. β‐amyloid.
Localization of Janusin mRNA in the Central Nervous System of the Developing and Adult Mouse
Authors: Wintergerst Eva Sabine , Fuss Babette , Bartsch Udo
Published: April 2006

Janusin (formerly termed J1‐160/180) is an oligodendrocyte‐derived extracellular matrix molecule which is restricted to the central nervous system and which is expressed late during development (Pesheva et al., J. Cell Biol., 1765 – 1778, 1989). To gain insights into the molecule's morphogenetic functions and to identify its cellular source in vivo, we have studied the localization of janusin messenger RNA in the optic nerve, retina and spinal cord and the expression of janusin protein in the spinal cord of developing and adult mice. Moreover, we have analysed optic nerve cell cultures and retinal cell suspensions in double‐labelling experiments using a janusin‐specific anti‐sense complementary RNA probe and cell type‐specific antibodies to identify the cell types containing janusin transcripts. In developing animals, oligodendrocytes were strongly labelled with the janusin anti‐sense cRNA probe during the period of myelination. The number of labelled cells and intensity of the hybridization signal decreased significantly with increasing age. Interestingly, expression of janusin was not confined to oligodendrocytes. Some neuronal cell types and type‐2 astrocytes present in optic nerve cell cultures also contained janusin transcripts. In contrast to oligodendrocytes, the number and labelling intensity of neurons containing janusin transcripts remained constant during postnatal development and into adulthood. Expression of janusin protein in the spinal cord was developmentally regulated, with a peak of expression in 2‐or 3‐week‐old animals. The molecule was visible in the white and grey matter. In myelinated regions, it was associated with myelinated fibres and accumulated at nodes of Ranvier. These observations suggest that janusin may be of functional relevance for myelination.
ME1 and GE1: Basic Helix – Loop – Helix Transcription Factors Expressed at High Levels in the Developing Nervous System and in Morphogenetically Active Regions
Authors: Neuman T. , Keen A. , Knapik E. , Shain D. , Ross M. , Nornes H. O. , Zuber M. X.
Published: April 2006

Several class A basic helix – loop – helix (bHLH) transcription factors have been cloned from the developing mouse and chick nervous system. The cloned cDNAs (ME1, ME2, ME3, ME4, in the mouse and GE1, GE2 in the chick) have HLH coding regions highly homologous to other known class A bHLH genes. The genes corresponding to ME1 and GE1 are abundantly expressed during development of the central nervous system. ME1 and GE1 are expressed in proliferating neuroblasts and in cells at the initial stages of differentiation (for example in the external granule cell layer of the cerebellum and in the lateral region of the ventricular zone in the developing neural tube and cortex). They are also expressed at high levels in morphogenetically active regions such as limb buds, somites and mesonephric tubules. The expression of ME1 and GE1 decreases once cellular differentiation is over. Based on the expression of ME1 and GE1 in regions of active cellular proliferation and differentiation and on the known role of other bHLH factors in development, we suggest that ME1 and GE1 play important roles during development of the nervous system as well as in other organ systems.
Changes in Nuclear 3,5,3′‐Triiodothyronine Receptor Expression in Rat Dorsal Root Ganglia and Sciatic Nerve During Development: Comparison with Regeneration
Authors: Barakat‐Walter I. , Due C. , Puymirat J.
Published: April 2006

The action of the thyroid hormones on responsive cells in the peripheral nervous system requires the presence of nuclear triiodothyronine receptors (NT3R). These nuclear receptors, including both the α and β subtypes of NT3R, were visualized by immunocytochemistry with the specific 2B3 monoclonal antibody. In the dorsal root ganglia (DRG) of rat embryos, NT3R immunoreactivity was first discretely revealed in a few neurons at embryonic day 14 (E14), then strongly expressed by all neurons at E17 and during the first postnatal week; all DRG neurons continued to possess clear NT3R immunostaining, which faded slightly with age. The peripheral glial cells in the DRG displayed a short‐lived NT3R immunoreaction, starting at E17 and disappearing from the satellite and Schwann cells by postnatal days 3 and 7 respectively. In the developing sciatic nerve, Schwann cells also exhibited transient NT3R immunoreactivity restricted to a short period ranging from E17 to postnatal day 10; the NT3R immunostaining of the Schwann cells vanished proximodistally along the sciatic nerve, so that the Schwann cells rapidly became free of detectable NT3R immunostaining. However, after the transection or crushing of an adult sciatic nerve, the NT3R immunoreactivity reappeared in the Schwann cells adjacent to the lesion by 2 days, then along the distal segment in which the axons were degenerating, and finally disappeared by 45 days, when the regenerating axons were allowed to re‐occupy the distal segment. It is concluded that (1) NT3R expression lasts throughout the life of the DRG neurons; (2) NT3R expression by peripheral glia is restricted to the perinatal period but may be transiently reactivated in Schwann cells after a nerve injury; and (3) cell‐cell interaction with axons down‐regulates the expression of NT3R by Schwann cells in both growing and regenerating nerves.
Effect of Thiol Reagents on Phosphoinositide Hydrolysis in Rat Brain Synaptoneurosomes
Authors: Vignes Michel , Guiramand Janique , Sassetti Isabelle , Récasens Max
Published: April 2006

Some divalent ions, such as Cd2+ and Zn2+, are able to stimulate phosphoinositide (PI) breakdown and to inhibit receptor‐mediated PI metabolism. These ions are also known to react with the free – SH groups of proteins. This prompted us to investigate the effects of more potent sulphhydryl reagents, Hg2+ and p‐chloromercuric benzosulphonic acid (PCMBS), on the inositol phosphate (IP) accumulation triggered by the neuroactive substances: glutamate, carbachol and K+, using synaptoneurosomes from 8‐day‐old rat forebrains. Hg2+ and PCMBS, depending on their concentration, had two distinct effects on IP accumulation: at low doses, Hg2+ (from 1 to 10 μM) and PCMBS (0.1 mM) by themselves stimulated PI breakdown, inhibited glutamate‐elicited IP accumulation and had additive effects with respect to carbachol‐induced IP stimulation. At higher doses, Hg2+ (from 0.01 to 1 mM) inhibited both basal and neuroactive substance‐stimulated IP accumulation. PCMBS (1 mM), provoked only an inhibition of the agonist‐stimulated IP formation. Monitoring membrane potential and intracellular Ca2+ with the fluorescent dyes diSC2(5) and fura2, respectively, indicated that these mercurials could strongly depolarize the synaptoneurosomal membrane and produce a Ca2+ influx dependent on extracellular Ca2+. The stimulatory effects of low concentrations of mercurials on PI turnover could be linked to the depolarization they provoke and the subsequent Ca2+ rise, which in turn is known to stimulate some phospholipase C enzymes. The inhibitory effects observed at high concentrations might be due to a loss of activity of proteins involved in PI breakdown, as all receptor‐mediated IP accumulations were inhibited.
The Development of Retinal Ganglion Cell Decussation Patterns in Postnatal Pigmented and Albino Ferrets
Authors: Thompson I. D. , Morgan J. E.
Published: April 2006

The decussation patterns of retinal ganglion cells in postnatal pigmented and albino ferrets were examined by using retrograde axonal tracers. Following unilateral injections into the optic pathway of newborn pigmented ferrets, ∼ 13 000 cells were labelled in the ipsilateral retina. The majority (11 500) of these were located in temporal retina. Postnatally, the numbers of cells projecting ipsilaterally from temporal retina fell by 49%. High rates of loss were observed in both the smaller uncrossed projection from nasal retina (92%) and also in the crossed projection from temporal retina (84%). After injections on the day of birth, a decussation line was not obvious in the crossed projection: ≥ 14 000 labelled cells were found in temporal retina. Double tracer studies showed that very few of these cells had axons which projected bilaterally. The numbers of ipsilaterally projecting cells labelled in neonatal albino ferrets was dramatically reduced. Only ∼ 2500 were labelled in temporal retina following injections at birth. As in pigmented ferrets, about half of these cells subsequently died. The reduced uncrossed projection in albino neonates was asociated with an increase in the crossed projection from temporal retina, in which ∼ 21 000 cells were labelled following injections at birth. These results suggest that differential postnatal ganglion cell death establishes the adult decussation pattern in the contralateral retinal projection but merely refines the pattern already established in the uncrossed projection. Postnatal ganglion cell death plays no significant role in generating the abnormal projections found in albino ferrets.
The Effects of Monocular Enucleation on Ganglion Cell Number and Terminal Distribution in the Ferret's Retinal Pathway
Authors: Thompson I. D. , Morgan J. E. , Henderson Z.
Published: April 2006

Anterograde and retrograde tracing techniques were used to examine the effects of removing one eye at birth on the remaining uncrossed retinal pathway in adult ferrets. After enucleation, the adult number of labelled ganglion cells projecting ipsilaterally changed from an average of 6068 in normal pigmented ferrets to an average of 7813 (29% increase) in pigmented enucleates. The change in albino ferrets was from 1455 in normals to 2319 in enucleates (59% increase). Labelled cells scattered across nasal retina accounted for over half the increase in the uncrossed population. After neonatal enucleation, the volume of lateral geniculate nucleus occupied by the uncrossed projection increased substantially, five‐fold in pigmented animals and 20‐fold in albinos. These results suggest that neonatal removal of one eye has a greater effect on the distribution of uncrossed terminals than on the survival of uncrossed ganglion cells. There was also an increase in the total number of axons in the surviving optic nerve of both pigmented and albino ferrets (93 000 in enucleates compared with 79 000 in normal animals), which cannot be simply explained as a disruption of binocular competition.
A High Degree of Spatial Selectivity in the Axonal and Dendritic Domains of Physiologically Identified Local‐circuit Neurons in the Dentate Gyms of the Rat Hippocampus
Authors: Han Zhong‐Sheng , Buhl Eberhard H. , Lörinczi Zoltan , Somogyi Peter
Published: April 2006

The axonal and dendritic domains of neurons with extensive, locally arborizing axons were delineated in the dentate gyrus of the rat hippocampus. In horizontally cut slice preparations neurons were briefly recorded and subsequently filled with biocytin when one or several of the following physiological properties were observed: (i) high‐amplitude short‐latency spike afterhyperpolarization; (ii) lack of spike frequency adaptation; (iii) high firing rate in response to depolarizing current. In a sample of 14 neurons, sufficient dendritic and/or axonal detail was recovered to identify them as non‐principal cells, i.e. non‐granule, non‐mossy cells. Five distinct types of cells were recognized, based on the spatial distribution of dendrites, presumably reflecting the availability of afferents, and on the basis of the highly selective distribution of their axon terminals, indicating synaptic target selectivity. They are: (1) the hilar cell forming a dense axonal plexus in the commissural and association pathway terminal field (HICAP cell; horizontal axon extent 1.6 mm) in the inner one‐third of the molecular layer, and having dendrites extending from the hilus to the top of the molecular layer; (2) the hilar cell with its axon ramifying in the perforant path terminal field (HIPP cell, horizontal axon extent 2.0 mm) in the outer two‐thirds of the molecular layer, whereas its spiny dendrites were restricted to the hilus; (3) the molecular layer cell with its dendritic and axonal domains confined to the perforant path terminal zone (MOPP cell, horizontal extent of axon 2.0 mm); (4) the dentate basket cell (horizontal axon extent 0.9 mm) had most of its axon concentrated in the granule cell layer, the remainder being localized in the inner molecular layer and hilus; (5) the hilar chandelier cell, or axo‐axonic cell (horizontal axon extent 1.1 mm), densely innervating the granule cell layer with fascicles of radially orientated terminal rows, and also forming an extensive plexus in the hilus. The three cell types having their somata in the hilus projected to granule cells at the same septo‐temporal level where their cell bodies were located. The results demonstrate that there is a spatially selective innervation of the granule cells by at least five distinct types of dentate neurons, which terminate in several instances in mutually exclusive domains. Their dendrites may have access to all (HICAP cell) or only a few (e.g. HIPP and MOPP cell) of the hippocampal afferents. This arrangement provides a framework for independent interaction between the output of local circuit neurons and subsets of excitatory afferents providing input to principal cells.
Current Source Density Profiles of Optical Recording Maps: a New Approach to the Analysis of Spatio‐temporal Neural Activity Patterns
Authors: Plenz Dietmar , Aertsen Ad
Published: April 2006

Spatio‐temporal spreading of activity in the CA1 region of the rat hippocampal slice was studied by two experimental approaches. At identical locations in the tissue we measured both the extracellular field potential distribution with microelectrode recordings and the intracellular potential distribution by optical recording, using voltage‐sensitive fluorescent dyes. Current source density analysis (CSD) was applied to the extracellular field potential distributions (eCSD) to enhance the spatial resolution. In order to obtain an analogous improvement for the optical recordings, we developed a new CSD transformation, which calculates the locations of the transmembrane current generators from the intracellular potential distributions (iCSD). Compared to the underlying fluorescence maps, the new iCSD profiles exhibit a considerable improvement in spatial resolution. Results can be directly interpreted in terms of physiological membrane processes, such as postsynaptic potentials and action potentials. The iCSD profiles show a surprisingly good correspondence with the classical eCSD profiles both qualitatively and quantitatively, the only difference being that cell body activity is reduced in amplitude. Thus, this new optical CSD analysis paves the way for a quantitative interpretation, rather than the hitherto predominantly qualitative interpretation of spatio‐temporal activity profiles from optical recording measurements.
Characterization of a Neurite Outgrowth Inhibitor Expressed After CNS Injury
Authors: Bovolenta Paola , Wandosell Francisco , Nieto‐Sampedro Manuel
Published: April 2006

Reactive gliosis, a general response to injury in the central nervous system grey and white matter, represents a serious obstacle to axonal regeneration in mammals. In culture, myelin‐free plasma membranes from normal rat brain tissue promoted neurite outgrowth, whereas myelin‐free membranes purified from injured tissue were inhibitory. The inhibitory activity could be solubilized by detergent, was sensible to glycosaminoglycan lyase digestion and eluted with an apparent molecular weight of 160 – 220 kDa in gel filtration chromatography. When presented as a surface‐bound molecule, the inhibitor prevented neurite initiation; when added in a soluble form to growing neurites, it induced their retraction. These results provide cellular and molecular evidence supporting the classical view that, in the mammalian central nervous system, damage‐evoked gliosis correlates with the expression of molecules capable of preventing neurite outgrowth.
The Neurotrophins BDNF, NT‐3 and NT‐4/5, But Not NGF, Up‐regulate the Cholinergic Phenotype of Developing Motor Neurons
Authors: Wong Vivien , Arriaga Ruth , Ip Nancy Y. , Lindsay Ronald M.
Published: April 2006

Although developing motor neurons express low‐affinity nerve growth factor (NGF) receptors, there is no known biological effect of NGF on developing or adult motor neurons. In this study, we found that, unlike NGF, brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3) and neurotrophin‐4/5 (NT‐4/5) stimulated cholinergic phenotype by increasing choline acetyltransferase (CAT) activity in cultures enriched with embryonic rat motor neurons. Ciliary neurotrophic factor (CNTF) also stimulated CAT activity. The effects of BDNF and NT‐4/5 on CAT activity appeared to be synergistic with that of CNTF. Cotreatment with BDNF and NT‐3 resulted in an additive effect, suggesting that signal transduction was mediated through different high‐affinity receptors tyrosine kinases B and C (Trk B and Trk C). However, cotreatment with BDNF and NT‐4/5 did not result in an increase in CAT activity greater than that of either BDNF or NT‐4/5 alone, suggesting that their effects were mediated via the same receptor Trk B. Supporting our findings that spinal cholinergic neurons are responsive to trophic actions of members of the neurotrophin family, motor neuron‐enriched cultures were found to express mRNA for Trk B and Trk C, which have been identified as high‐affinity receptors for BDNF and NT‐4/5, and NT‐3, respectively.
Effects of Intracortical Infusion of Anticholinergic Drugs on Neuronal Plasticity in Kitten Striate Cortex
Authors: Gu Qiang , Singer Wolf
Published: April 2006

During a critical period of postnatal development the mammalian visual cortex is highly susceptible to experience‐dependent alterations of neuronal response properties. These modifications are facilitated by the neuromodulators noradrenalin and acetylcholine. To identify the cholinergic mechanisms responsible for this facilitation, muscarinic and nicotinic antagonists were infused into the visual cortex of kittens while the animals were subject to monocular deprivation. Subsequently the ocular dominance of cortical cells was assessed by single‐unit recording. Ocular dominance changes were suppressed by scopolamine and pirenzepine but not by gallamine, hexamethonium and mecamylamine. This blocking effect was concentration‐dependent, and control experiments revealed that it was not due to suppression of neuronal responses to light. It is concluded from these results that acetylcholine facilitates neuronal plasticity in the visual cortex through mechanisms activated by muscarinic M1receptors.
Retinal Projections to the Pretectum, Accessory Optic System and Superior Colliculus in Pigmented and Albino Ferrets
Authors: Zhang H. Y. , Hoffmann K.‐P.
Published: April 2006

Retinal projections to the pretectal nuclei, accessory optic system and superior colliculus in pigmented and albino ferrets were studied using anterograde tracing techniques. Both Nissl‐ and myelin‐stained material was used to identify the pretectal nuclei, nuclei of the accessory optic system and the layers of the superior colliculus. Following monocular injection of either horseradish peroxidase or rhodamine‐B‐isothiocyanate, four pretectal nuclei, including the nucleus of the optic tract, posterior pretectal nucleus, anterior pretectal nucleus and the olivary pretectal nucleus, could be identified to receive direct retinal input in both pigmented and albino strains. In the accessory optic system, retinal terminals were observed in the dorsal, lateral and medial terminal nuclei as well as in the interstitial nucleus of the superior fasciculus, posterior fibres. The retinal projection to the superior colliculus was found to innervate the three superficial layers. The retinal projections to the pretectal nuclei and nuclei of the accessory optic system in the pigmented animals were bilateral, although the label was most dense contralateral to the injected eye. Ipsilateral retinal projections to the pretectal nuclei and nuclei of the accessory optic system appeared to be absent in albino ferrets, i.e. they were invisible with our methods. In both pigmented and albino ferrets retinal terminals in the contralateral superior colliculus densely innervated the three superficial layers. In both strains the ipsilateral projection appeared as clusters which were absent in rostral and caudal poles. In pigmented animals the ipsilateral projection was much denser and more extensive than in albinos. Following injection of retrograde tracers into the brainstem at the level of the dorsal cap of the inferior olive, retrogradely labelled neurons in the pretectum were found in the ipsilateral nucleus of the optic tract. Their somata overlapped mainly with scattered retinal terminals close to the pretectal surface and rarely or not all with the deeper prominent terminal clusters. In the accessory optic system, inferior olive projecting neurons were observed in all four ipsilateral nuclei and fully coincided with the retino‐recipient zones. In the superior colliculus, retrogradely labelled neurons were found contralateral to the injection site in the deep layers.
Squint Affects Synchronization of Oscillatory Responses in Cat Visual Cortex
Authors: König Peter , Engel Andreas K. , Löwel Siegrid , Singer Wolf
Published: April 2006

As shown previously, neurons in various areas of the cat's visual cortex respond to appropriate visual stimuli with oscillatory activity in the frequency range of 30 – 70 Hz. It has been suggested that synchronization of such responses serves to define assemblies of coherently active cells which represent individual visual objects. In this study, we have investigated this putative binding mechanism in the visual cortex of strabismic cats. We used six adult cats in which divergent squint had been induced surgically at the age of 3 weeks. Multiunit activity was recorded from area 17 with arrays of four or five closely spaced microelectrodes. Subsequently, auto‐ and cross‐correlation functions were computed for all spike trains. To quantify the oscillatory nature of the responses and the strength of synchronization between spatially remote sites, damped sine wave functions were fitted to the correlograms. Analysis of responses obtained from 202 recording sites showed that the vast majority of cells had become monocular. Auto‐correlation analysis revealed that the proportion of oscillatory firing patterns was similar to that observed in normal cats. However, cross‐correlation analysis of 153 response pairs demonstrated that synchronization was reduced significantly between cells dominated by different eyes while it was as frequent and strong as in normal cats between cells dominated by the same eye. These findings indicate that strabismus not only causes a reorganization of afferent inputs but also affects intracortical interactions. Since strabismic cats lack tangential intracortical connections between territories connected to different eyes and are unable to combine signals conveyed by the two eyes these results support the notion that response synchronization is achieved by cortico‐cortical connections and serves as a mechanism for feature binding.