bluuebunny/crossref_metadata_2025 huggingface dataset:
The Organization of Projections from Subdivisions of the Auditory Cortex and Thalamus to the Auditory Sector of the Thalamic Reticular Nucleus in Galago
Authors: Conley Michael , Kupersmith Andrew C. , Diamond Irving T.
Published: April 2006

Anterograde and retrograde transport techniques were used to study the connexions between different subdivisions of the auditory cortex and thalamus with the thalamic reticular nucleus in the prosimian, Galago. In particular, the goal was to determine whether the primary auditory nucleus, GMv, and its cortical target, area I of the auditory cortex (A I), project to a different region of the auditory sector of the reticular nucleus from the secondary auditory nuclei, GMmc and Po and their cortical targets outside A I. The results show that the projections to and from the auditory sector are indeed segregated: injections of wheatgerm agglutinin‐conjugated horseradish peroxidase into either GMmc or Po labelled cells and terminals along the medial, lateral and ventral borders of the auditory sector, forming a U‐shaped pattern. Projections from area II of the auditory cortex produced almost an identical pattern of the terminal labelling in the auditory sector. In contrast, injections into GMv‐labelled cells and terminals in the centre region of the auditory sector, in the ‘interior’ of the U‐shaped region. Projections from A I were distributed to both the U‐shaped border region and the central core of the auditory sector probably because A I received projections from GMmc, Po and GMv. The significance of these results depends on a comparison between the auditory and visual sectors of the reticular nucleus. Both sectors are divided into tiers or subsectors–one related to the primary relay nucleus, i.e. GLd or GMv, and the other related to the secondary relay nuclei, i.e. pulvinar nucleus, GMmc, Po, etc.
Axons Sprout and Microtubules Increase After Local Inhibition of RNA Synthesis, and Microtubules Decrease after Inhibition of Protein Synthesis: A Morphometric Study of Rat Sural Nerves
Authors: Bustos Jorge , Vial Juan D. , Faúndez Victor , Alvarez Jaime
Published: April 2006

Drugs that inhibit RNA or protein synthesis are known to affect some functional properties of axons. In this context, we studied the ultrastructural effects of actinomycin‐D, an inhibitor of RNA synthesis, and cycloheximide and emetine, inhibitors of protein synthesis, in rat sural nerves. A silicone sleeve (4 mm long) loaded with drug was placed around the nerves and left for about a week. The ultrastructural alterations of axons and Schwann cells progressed over this period. After cycloheximide and emetine, the cytoplasm of Schwann cells was enlarged and the rough endoplasmic reticulum was prominent. After actinomycin‐D, the Schwann cells reached the stage of lysis. Nonmedullated were more affected than myelinated axons. After cycloheximide and emetine, the axoplasmic matrix decreased substantially but reversibly. Microtubules of nonmedullated fibres decreased by about 50%. Actinomycin‐D determined sprouting of axons and a rise of axonal microtubules; in nonmedullated axons, the normal inverse correlation between microtubular density and calibre gave way to a high and constant density for all axonal sizes. A few millimetres proximal and distal to the sleeve, the nerve tissue and the axonal microtubular content were close to normal, i.e. the effects of drugs were local. Present results suggest that the local turnover of amino acids in the axon is necessary to maintain the integrity of microtubule and neurofilament proteins. We propose that the Schwann cell down‐regulates the axonal cytomatrix.
Differential Distribution of Tau Proteins in Developing Cat Cerebral Cortex and Corpus Callosum
Authors: Riederer Beat M. , Innocenti Giorgio M.
Published: April 2006

During the postnatal development of cat visual cortex and corpus callosum the molecular composition of tau proteins varied with age. In both structures, they changed between postnatal days 19 and 39 from a set of two juvenile forms to a set of at least two adult variants with higher molecular weights. During the first postnatal week, tau proteins were detectable with TAU‐1 antibody in axons of corpus callosum and visual cortex, and in some perikarya and dendrites in the visual cortex. At later ages, tau proteins were located exclusively within axons in all cortical layers and in the corpus callosum. Dephosphorylation of postnatal day 11 cortical tissue by alkaline phosphatase strongly increased tau protein immunoreactivity on Western blots and in numerous perikarya and dendrites in all cortical layers, in sections, suggesting that some tau forms had been unmasked. During postnatal development the intensity of this phosphate‐dependent somatodendritic staining decreased, but remained in a few neurons in cortical layers II and III. On blots, the immunoreactivity of adult tau to TAU‐1 was only marginally increased by dephosphorylation. Other tau antibodies (TAU‐2, B19 and BR133) recognized two juvenile and two adult cat tau proteins on blots, and localized tau in axons or perikarya and dendrites in tissue untreated with alkaline phosphatase. Tau proteins in mature tissue were soluble and not associated with detergent‐resistant structures. Furthermore, dephosphorylation by alkaline phosphatase resulted in the appearance of more tau proteins in soluble fractions. Therefore tau proteins seem to alter their degree of phosphorylation during development. This could affect microtubule stability as well as influence axonal and dendritic differentiation.
Cytotoxic Effect of Brain Macrophages on Developing Neurons
Authors: Théry Clotilde , Chamak Brigitte , Mallat Michel
Published: April 2006

Brain macrophages are transiently present in different regions of the central nervous system during development or in the course of tissue remodelling following various types of injuries. To investigate the influence of these phagocytes on neuronal growth and survival, brain macrophages stemming from the cerebral cortex of rat embryos were added to neuronal primary cultures. A neurotoxic effect of brain macrophages was demonstrated by the reduction of the number of neurons bearing neurites within two days of contact between the two cell types. Neuronal death and phagocytosis were also directly observed in video recordings of living cultures. This toxicity involved the production by brain macrophages of reactive oxygen intermediates, as shown by the protective effect of catalase, a scavenger of H2O2. In addition, the respiratory bursts of brain macrophages were stimulated in the presence of neurons. These results suggest that brain macrophages could favour the appearance of neuroregressive events which occur either during neurogenesis or in neurodegenerative diseases, implying intracerebral recruitment of mononuclear phagocytes.
Facilitation and Delay Sensitivity of Auditory Cortex Neurons in CF‐FM Bats, Rhinolophus rouxi and Pteronotus p.parnellii
Authors: Schuller G. , O'Neill W. E. , Radtke‐Schuller S.
Published: April 2006

Responses of auditory neurons to complex stimuli were recorded in the dorsal belt region of the auditory cortex of two taxonomically unrelated bat species, Rhinolophus rouxi and Pteronotus parnellii parnellii, both showing Doppler shift compensation behaviour. As in P.p.parnellii (Suga et al., J. Neurophysiol, 49, 1573–1626, 1983), cortical neurons of R. rouxi show facilitated responses to pairs of pure tones or frequency modulations. Best frequencies for the two components lie near the first and second harmonic of the echolocation call but are in most cases not harmonically related. Neurons facilitated by pairs of pure tones show little dependence on the delay between the stimuli, whereas pairs of frequency modulations evoke best facilitated responses at distinct best delays between 1 and 10 ms. Facilitated neurons are found in distinct portions of the dorsal cortical belt region, with a segregation of facilitated neurons responding to pure tones and to frequency modulations. Non‐facilitated neurons are found throughout the field. Neurons are topographically aligned with increasing best delays along a rostrocaudal axis. The best delays between 2 and 4 ms are largely overrepresented numerically, and occupy ˜56% of the cortical area containing facilitated neurons. A functional interpretation of the large overrepresentation of best delays ˜3ms is proposed. Facilitated neurons are located almost entirely within layer V of the dorsal field.
The Gene for Ciliary Neurotrophic Factor (CNTF) Maps to Murine Chromosome 19 and its Expression is Not Affected in the Hereditary Motoneuron Disease ‘Wobbler’ of the Mouse
Authors: Kaupmann Klemens , Sendtner Michael , Stöckli Kurt A. , Jockusch Harald
Published: April 2006

The cDNA for ciliary neurotrophic factor (CNTF), a polypeptide involved in the survival of motoneurons in mammals, has recently been cloned (Stöckli et al., Nature, 342, 920–923, 1989; Lin et al Science, 246, 1023–1025, 1989). We have now localized the corresponding gene Cntf to chromosome 19 in the mouse, using an interspecific cross between Mus spretus and Mus musculus domesticus. The latter was carrying the gene wobbler (wr) for spinal muscular atrophy. DNA was prepared from backcross individuals and typed for the segregation of species‐specific Cntf restriction fragments in relation to DNA markers of known chromosomal location. The M.spretus allele of Cntf cosegregated with chromosome 19 markers and mapped closely to Ly‐1 to a region of mouse chromosome 19 with conserved synteny to human chromosome 11q. Cntf is not linked to wr, and the expression of CNTF mRNA and protein appears close to normal in facial and sciatic nerves of affected (wr/wr) mice, suggesting that motoneuron degeneration of wobbler mice has its origin in defects other than reduced CNTF expression.
Monosynaptic Interjoint Reflexes and their Central Modulation During Fictive Locomotion in Crayfish
Authors: El Manira A. , DiCaprio R. A. , Cattaert D. , Clarac F.
Published: April 2006

An in vitro preparation of the crayfish nervous system has been utilized to study an interjoint reflex pathway and its variability during rhythmic locomotor activity. The coxo‐basal chordotonal organ (CBCO) is a joint stretch receptor spanning the second joint of walking legs in crayfish, where it encodes joint movements and position. Mechanical stimulation (stretch and release) of the CBCO and electrical stimulation of the CBCO nerve elicits reflex responses in promotor and remotor motor neurons innervating muscles moving the basal thoraco‐coxal (TC) leg joint. Promotor and remotor motor neurons receive monosynaptic excitatory inputs from at least four CBCO afferents, including both stretch‐ and release‐sensitive CBCO afferents. In a tonic preparation, in which there is no tendency to produce alternating bursts of activity in antagonistic motor neurons, the reflex responses were evoked during each cycle of imposed movement. However, when the preparation became rhythmic and produced bouts of fictive locomotion, the reflex responses were unstable and their gain was phasically modulated. Paired recordings indicate that such a modulation of the monosynaptic interjoint reflex could be due to both a phasic change in the excitability of the motor neurons and presynaptic inhibition that reduces the excitatory input from CBCO primary afferents.
Aspartate‐ and Glutamate‐like Immunoreactivities in Rat Hippocampal Slices: Depolarization‐induced Redistribution and Effects of Precursors
Authors: Gundersen V. , Ottersen O. P. , Storm‐Mathisen J.
Published: April 2006

The light microscopic localization of aspartate‐like immunoreactivity (Asp‐LI) was compared to that of glutamate‐like immunoreactivity (Glu‐LI) in hippocampal slices by means of specific polyclonal antibodies recognizing the amino acids fixed by glutaraldehyde. After incubation in Krebs' solution with normal (5 mM) or depolarizing concentrations of K+, and various additives, the slices were fixed with glutaraldehyde, resectioned and processed according to the peroxidase ‐ antiperoxidase procedure. At 5 mM K+, Glu‐LI was localized in nerve‐terminal like dots with a conspicuous laminar distribution, the highest Glu‐LI concentrations coinciding with the terminal fields of major excitatory pathways thought to use glutamate or aspartate as transmitters. The localization of Asp‐LI showed some similarity to that of Glu‐LI, but the laminar distribution was less differentiated and the immunoreactivity was much weaker. At 40 and 55 mM K+ the nerve terminal localizations of Glu‐LI and Asp‐LI were strongly reduced. Concomitantly, both immunoreactivities appeared in astroglial cells. These changes were Ca2+‐dependent. The nerve ending staining patterns of Asp‐LI and Glu‐LI could be sustained during depolarization if the medium was supplemented with glutamine (0.5 mM). Under these conditions Asp‐LI became more intense and its distribution approached that of Glu‐LI. This suggests that, when stimulated, some nerve endings can increase their reservoir of releasable aspartate. The presence of glutamine during depolarization strongly reduced glial Asp‐LI and Glu‐LI, possibly due to its providing nitrogen for conversion of glutamate to glutamine. α‐Ketoglutarate, another glia‐derived precursor of neuronal glutamate, was virtually ineffective in supporting Glu‐LI and Asp‐LI in nerve endings, and did not suppress Glu‐LI or Asp‐LI in glia. Our findings provide morphological support for the view that excitatory nerve endings under certain conditions can contain high levels of both aspartate and glutamate (possibly in the same terminals), and that aspartate as well as glutamate can be released synaptically. Further, they underline the importance of the glial supply of the nerve endings with precursor glutamine, which allows them to build up and sustain high concentrations of transmitter amino acids during release.
Localization of Sequences Determining Cell Type Specificity and NGF Responsiveness in the Promoter Region of the Rat Choline Acetyltransferase Gene
Authors: Ibáñez Carlos F. , Persson Håkan
Published: April 2006

A genomic clone containing 7 kb of 5’flanking sequences from the rat choline acetyltransferase (ChAT) gene was isolated and shown to contain a TATA box‐like sequence and several consensus binding sites for the transcription factor AP1. Two constructs containing 450 and 1450 base pairs (bp), respectively, of 5’flanking sequences promoted expression of a fused chloramphenicol acetyltransfersase (CAT) gene when transfected into fibroblast FR3T3, Sertoli TM4, phaeochromocytoma PC12 and cholinergic neuronal SN6 cell lines. In contrast, a longer construct containing 3850 bp of 5’flanking sequence allowed CAT activity only in the cholinergic cell line SN6. CAT activity with this construct was suppressed in the three other cell lines, indicating that the distal region of the ChAT promoter contains a cell type‐specific silencer‐like element that restricts ChAT gene expression to cholinergic cells. Treatment of PC12 cells with nerve growth factor (NGF) increased the promoter activity of the ‐450 and ‐1450 constructs approximately four‐fold and allowed promoter activity from the ‐3850 construct, indicating that elements involved in NGF responsiveness of the ChAT promoter are contained in the first 450 bp of upstream sequence. These results support a model in which gene transcription controlled by cell‐type specific regulatory elements contribute to the establishment, maintenance and plasticity of the cholinergic transmitter phenotype in the nervous system.
Complementary Distribution of Calbindin D‐28k and Parvalbumin in the Basal Forebrain and Midbrain of the Squirrel Monkey
Authors: Côté Pierre‐Yves , Sadikot Abbas F. , Parent André
Published: April 2006

The distribution of cell bodies expressing either calbindin D‐28k or parvalbumin immunoreactivity in the basal forebrain and midbrain of squirrel monkeys (Saimiri sciureus) was studied on contiguous sections incubated with monoclonal antibodies raised against calbindin or parvalbumin. In the nucleus accumbens, medium‐sized calbindin‐positive neurons formed two cell bridges joining the ventral part of the striatum to the olfactory tubercle, whereas medium‐sized parvalbumin‐positive cells in the same area were much less numerous and more uniformly distributed. The medial and dorsal septal nuclei contained a small number of elongated calbindin‐positive neurons and only a few parvalbumin‐immunoreactive cells. In the nucleus of the diagonal band of Broca, calbindin and parvalbumin were found to label two distinct but closely intermingled neuronal populations. In the striatum, medium‐sized calbindin‐immunoreactive cells occurred in very large numbers and appeared to be confined to the extrastriosomal matrix. Medium‐sized, parvalbumin‐immunoreactive neurons were also present in the striatum but they were less numerous than the calbindin‐positive cells. The calbindin‐positive neurons in the dorsal portion of the striatum were less intensely stained than those in the ventral portion, whereas this pattern did not occur for neurons expressing parvalbumin immunoreactivity. At the pallidal level, neurons in both segments were devoid of calbindin but displayed a very strong parvalbumin immunoreactivity. Most of the large neurons of the nucleus basalis of Meynert were strongly calbindin‐immunoreactive and many of them invaded dorsally the medullary laminae of the pallidal complex. The neurons of the subthalamic nucleus were markedly enriched with parvalbumin but displayed only light calbindin staining. In the substantia nigra/ventral tegmental area complex, calbindin‐immunoreactive cells abounded in the ventral tegmental area and in the dorsal tier of the pars compacta of the substantia nigra, but were absent in the ventral tier of the pars compacta and in the entire pars reticulata of the substantia nigra. In contrast, numerous parvalbumin‐immunoreactive neurons occurred in the pars reticulata and pars lateralis, but none were found in the pars compacta and ventral tegmental area. These findings reveal that the patterns of calbindin and parvalbumin distribution in primate basal forebrain and midbrain are strikingly complementary, suggesting a synergistic role for these calcium‐binding proteins in basal forebrain and midbrain function.
Serotonin Reinnervation of the Suprachiasmatic Nucleus by Intrahypothalamic Fetal Raphe Transplants, with Special Reference to Possible Influences of the Target
Authors: Daszuta Annie , Marocco Céile , Bosler Olivier
Published: April 2006

Survival and development of fetal serotonin (5‐HT) neurons grafted to various brain areas in adult mammals have been suggested to be under host influences. The aim of this study was to determine whether the suprachiasmatic nucleus of the hypothalamus (SCN), a region receiving a 5‐HT input which is one of the densest and the most heavily synaptic in the brain, can actually support the development of transplanted 5‐HT neurons. The time course and extent of 5‐HT reinnervation were therefore investigated with 5‐HT immunocytochemistry in adult rats subjected to intraventricular injection of 5,7‐dihydroxytryptamine and subsequent grafting of fetal cell suspension of mesencephalic raphe neurons. The ultrastructural features of the newly formed 5‐HT terminal plexa were also examined. Serotonin reinnervation of the SCN remained partial up to 4 months post‐transplantation, with no apparent predilection of the reinnervating fibres for any particular portion of the nucleus, thus differing from the normal 5‐HT innervation of the SCN both quantitatively and qualitatively. This was in sharp contrast to the 5‐HT hyperinnervation observed in neighbouring areas such as the supraoptic nucleus, a structure normally provided with only few 5‐HT fibres, and the ventral wall of the third ventricle. The graft‐derived 5‐HT‐axons, however, displayed ultrastructural features that did not appear different from those of their normal counterparts; in particular they re‐established defined synaptic contacts with the host population. These results may indicate that the mature SCN specifically lacks a trophic factor necessary for the ingrowth of graft‐derived 5‐HT fibres, or that it represents an inhibitory environment for such an ingrowth. The limited ability of regrowing 5‐HT axons to restore a normal density of 5‐HT innervation could also be related to the fact that these neurons normally establish a relatively high number of synaptic contacts in the target region.
The Distribution of μ and δ Opioid Binding Sites Belonging to a Single Cervical Dorsal Root in the Superficial Dorsal Horn of the Rat Spinal Cord: A Quantitative Autoradiographic Study
Authors: Besse D. , Lombard M. C. , Besson J. M.
Published: April 2006

Numerous studies have demonstrated a dense concentration of opioid receptors in the superficial layers (laminae I‐II) of the spinal cord. These receptors are located both pre‐ and postsynaptically at this level. The purpose of this study was to assess the distribution of opioid receptors belonging to a single (C7) dorsal root. Thus, quantitative autoradiography of γ ([3H]Tyr‐d‐Ala‐Gly‐NMe‐Phe‐Gly‐ol; [3H]DAMGO) and δ ([3H]Tyr‐d‐Thr‐Gly‐Phe‐Leu‐Thr; [3H]DTLET) opioid binding sites was performed for several experimental groups: control rats with intact dorsal roots and lesioned rats with a unilateral dorsal rhizotomy of (a) the C7 root alone, (b) the three successive roots rostral and caudal to the spared C7 root, and (c) the seven roots C4‐Th2. By subtracting results of the ‘C7 cut’ group from the ‘intact’ group or by subtracting results of the C4‐Th2 cut group from the C7 spaced group, it was possible to measure the distribution of γ. and δ opioid binding sites belonging to the C7 root. The combination of these two methods of calculation allowed us to demonstrate a significant distribution over two segments rostral and one segment caudal to the segment of entry. For [3H]DAMGO, the distribution was 10% (P < 0.05) in the C5, 27%, (P < 0.001) in the C6, 38% (P < 0.001) in the C7 and 14% (P < 0.05) in the C8 segment. For [3H]DTLET, the distribution was 11% (P= 0.05) in the C5, 27%, (P < 0.01) in the C6, 37% (P < 0.001) in the C7 and 18% (P < 0.05) in the C8 segment. It is also noted that rostral distributions spread more densely and further than the caudal ones.
Activation of N‐methyl‐D‐aspartate Receptors Induces Endogenous Rhythmic Bursting Activities in Nucleus Tractus Solitarii Neurons: An Intracellular Study on Adult Rat Brainstem Slices
Authors: Tell Fabien , Jean André
Published: April 2006

A brainstem slice preparation and intracellular recording techniques were used to examine the effects of N‐methyl‐D‐aspartate (NMDA) application on neurons within the swallowing area of the nucleus tractus solitarii (NTS). According to their cellular properties, NTS neurons were classified into type I and type II neurons. The most striking difference was the occurrence of delayed excitation in type I but not in type II neurons, when they were depolarized from membrane potentials more negative than ‐60 mV. Bath application of NMDA (30–60 μM) elicited depolarization and triggered stable repetitive firing in all the NTS neurons but one. During the NMDA‐induced depolarization, hyperpolarization below ‐60 mV elicited, in some type I neurons, a rhythmic bursting pattern. The duration of the bursts (300–1000 ms) and their frequency (0.5–2 Hz) depended on the membrane potential. With hyperpolarizations below ‐75 mV, rhythmic bursting was converted into rhythmic single discharges, a pattern elicited directly in the other type I neurons. In all cases, rhythmic patterns were superimposed on cyclic depolarizations of the membrane potential characterized by an initial ramp‐shaped phase. In type II neurons, rhythmic bursting discharges, superimposed on rhythmic oscillations of the membrane potential, were also obtained upon hyperpolarization during the NMDA‐induced depolarization. In all type I neurons tested, NMDA‐induced cyclic ramp‐shaped depolarizations continued after addition of tetrodotoxin to the medium. Rhythmic bursting was not elicited by bath application of kainate (10–20 μM). Application of D‐2‐amino‐5‐phosphonovalerate (50 μM) blocked NMDA‐induced depolarizations without modifying those elicited by kainate, which were selectively depressed by 6‐cyano‐7‐nitroquinoxaline‐2, 3‐dione (10 μM). Moreover, removal of Mg2+ from the medium suppressed NMDA‐induced cyclic depolarizations. Results demonstrate that both NMDA and non‐NMDA receptors are present in NTS neurons and that selective activation of NMDA receptors induced rhythmic bursting and/or rhythmic single discharges. Rhythmic patterns were not driven by synaptic mechanisms but originated from endogenous properties of NTS neurons activated by NMDA. Thus, NTS neurons can be considered as conditional pacemakers. According to the location of the neurons, the conditional properties shown in these in vitro experiments might be involved in vivo in the generation of rhythmic motor activities set up at the NTS level, such as swallowing.
Poor Growth of Mammalian Motor and Sensory Axons Into Intact Proximal Nerve Stumps
Authors: Brown M. C. , Lunn E. R. , Perry V. H.
Published: April 2006

Wallerian degeneration is very slow in the mouse strain now known as C57BL/Ola. Sensory axon regrowth following peripheral nerve lesions is very poor in these animals but motor axons succeed in reinnervating the distal nerve stump even while the majority of severed axons are still intact (Lunn et al Eur. J. Neurosci., 1, 27–33, 1989). To see if motor axons could grow into a completely undegenerated portion of nerve, the proximal stumps of the peroneal and tibial nerves were sutured together in six BALB/c mice and the ability of large motor and sensory fibres from the tibial nerve to grow into the peroneal nerve was examined electrophysiologically in four of them. For the acute experiment the peroneal nerve was cut ‐ 7 mm central to the point of suture to the tibial nerve. Both at 2 weeks and 7 weeks after surgery the size of the potential recorded in the ventral roots on stimulating the portion of peroneal nerve into which tibial axons were directed to grow was only ‐8% of the potential recorded when the tibial nerve was itself stimulated. The potential recorded in the dorsal roots was only ‐2%. Counts of axon numbers in electron micrographs showed a small but non‐significant increase over normal in the number of unmyelinated axons in the peroneal nerves which’ had been connected to the tibial nerve in this way. It is concluded, in agreement with Langley and Anderson (J. Physiol., 31, 365–391, 1904), that axon growth into intact nerves is extremely limited in mammals and that the distal nerve stump of C57BL/Ola mice, although it degenerates very slowly, is not therefore equivalent to an intact peripheral nerve.
Presynaptic GABAA and GABAB Receptor‐mediated Phasic Modulation in Axons of Spinal Motor Interneurons
Authors: Alford Simon , Christenson Johan , Grillner Sten
Published: April 2006

The lamprey spinal cord has been utilized to investigate the role of presynaptic inhibition in the control of the spinal motor system. Axons of the lamprey spinal cord are comparatively large because of their lack of myelination. Axons impaled with microelectrodes demonstrate depolarizing responses to the application of GABAA and GABAB receptor agonists, muscimol and baclofen. These depolarizing effects are counteracted by the specific GABAA and GABAB receptor antagonists, bicuculline and phaclofen. GABAA receptor activation leads to a gating of Cl− channels on the axons. However, the ionic mechanism leading to axonal depolarization following GABAB receptor activation is unknown. After initiation of fictive locomotion, these axons demonstrate oscillations in axonal membrane potential related to the locomotor cycle. During ficitive locomotion they depolarize in phase with the bursting of the ipsilateral ventral root of the same segment. These axonal membrane potential oscillations are due to a phasic GABAA and GABAB receptor‐mediated gating of ion channels on the axonal membrane. Fictive locomotion in the lamprey spinal cord is largely unaffected by antagonism of one or other GABA receptor subtype alone, but is severely disrupted by simultaneous antagonism of both subtypes. In conclusions, we demonstrate, for the first time, an agonist‐gated depolarization of a vertebrate presynaptic element measured by direct impalement of the axon under study. We also demonstrate that GABA‐mediated presynaptic inhibition occurs in axons of spinal interneurons. It is not limited to the primary afferents as has previously been believed.
A Monoclonal Antibody Defining a Carbohydrate Epitope Restricted to Glial Cells
Authors: Cameron‐Curry Patrizia , Dulac Catherine , Le Douarin Nicole M.
Published: April 2006

To follow cell lineage segregation of glial cell precursors in the central and peripheral nervous systems (CNS and PNS), we made monoclonal antibodies against purified avian myelin glycoproteins and made detailed studies of antibodies reacting with cellular antigens expressed early in development. We describe here the cellular and molecular characterization of the 4B3 epitope, which is first expressed at day 2.5 in quail embryos and appears strictly specific to glial cell membranes in the PNS and CNS. We demonstrate that, not only oligodendrocytes and astrocytes but also myelinating and non‐myelinating Schwann cells, satellite cells of sensory and autonomic ganglia and enteric glial cells are 4B3‐positive. This epitope was identified as an N‐linked carbohydrate determinant shared by several unrelated molecules, one of them already described as the SMP glycoprotein.
Chronic Suppression of Bioelectric Activity and Cell Survival in Primary Cultures of Rat Cerebral Cortex: Biochemical Observations
Authors: Ramakers G. J. A. , Boer G. J.
Published: April 2006

Chronic suppression of spontaneously occurring bioelectric activity (BEA) has been shown to increase neuronal cell death in tissue culture, but may also affect astrocytes. We investigated this process in primary cultures of rat cerebral cortex by measuring the levels of NSE (neuron‐specific enolase) and GFAP (glial fibrillary acidic protein) in relation to general tissue markers, including measurements for cell death and proliferation. In electrically active (control) cultures, the content of DNA, protein, and NSE became maximal between 21 and 28 days in vitro (DIV) and thereafter decreased, whereas the content of GFAP rose continuously up to 43 DIV. Chronic suppression of BEA by tetrodotoxin (TTX; from 6 DIV) decreased the content of DNA, total protein, and especially NSE. The content of GFAP was decreased in all culture series investigated, but with great temporal variations among culture series. Chronic TTX treatment (started at 6 DIV) increased the efflux of lactate dehydrogenase, a marker for cell lysis, between 12 and 21 DIV, but this efflux was mainly derived from the supporting glial cells with which the cerebral cortex cultures were cocultured. Chronic, but not acute (7 h) TTX treatment decreased total [3H]thymidine incorporation into DNA from 14 DIV; this appeared to be due to a reduced number of astrocytes. Chronic suppression of BEA with xylocaine from 6 DIV had similar effects on DNA‐, protein‐, and NSE‐content as TTX, but led to an increased content of GFAP at 21 DIV. Chronic suppression of synaptic transmission with 10 mM Mg2+ and 0.2 mM Ca2+, starting at 6 DIV, increased the content of DNA, protein, and GFAP at 21 DIV, but NSE was still decreased. We conclude that chronic suppression of BEA in cerebral cortex cultures enhances neuronal cell death, whereas astrocytes are differentially affected, depending on the suppressing agent. As astrocytes may have a modulating effect on neuronal survival, their involvement should be regarded when studying the effects of chronic suppression of BEA on neuronal development.
Impaired Learning and Abnormal Open‐field Behaviours of Rats After Early Postnatal Anoxia and the Beneficial Effect of the Calcium Antagonist Nimodipine
Authors: Nyakas C. , Markel Éva , Schuurman T. , Luiten P. G. M.
Published: April 2006

Perinatal anoxia/hypoxia is considered a serious risk factor for normal brain development. Anoxia induced by repeated asphyxia at 2 and 4 days after birth resulted in a transient hyperactivity in the small open‐field, and a behavioural depression in adult open‐field activity of male Wistar rats. The same treatment impaired adult learning behaviour in pole‐jumping conditioned avoidance and appetitively motivated hole‐board test situations. The calcium entry blocker nimodipine (in doses of 3 and 10 mg/kg) prevented the anoxia‐induced changes in orientation motility in the open‐field tests and almost fully antagonized the learning deficit in the hole‐board test. The behavioural deficit seen during acquisition of the pole‐jumping conditioned avoidance response was ameliorated to a lesser degree. The results indicate that the maintenance of calcium homeostasis during the early postnatal phase of brain development is crucial to prevent anoxia‐induced behavioural abnormalities.
Comparative Distribution of Neurons Containing FLFQPQRFamide‐like (morphine‐modulating) Peptide and Related Neuropeptides in the Rat Brain
Authors: Kivipelto Leena , Panula Pertti
Published: April 2006

FLFQPQRF‐NH2 (F8Famide; morphine‐modulating peptide), isolated from bovine brain, is an FMRFamide‐like peptide with opioid analgesia modulating effects. In the rat brain, F8Famide is immunohistochemically localized in neurons of the medial hypothalamus and medulla oblongata. Neuropeptide Y (NPY) is structurally related to F8Famide and the mammalian FMRFamide‐like immunoreactivity (LI) was once thought to be due to an NPY‐like peptide. We compared the anatomical distribution of F8Famide‐LI with the localization of enkephalin‐ and NPY‐LI‐containing structures in the rat brain to find out if NPY or enkephalins coexist with F8Famide‐LI. Cryostat sections of colchicine‐treated Wistar rat brains were incubated with specific antisera against F8Famide, NPY, YGGFMRGL (Met‐enkephalin‐Arg‐Gly‐Leu), or YGGFMRF (Met‐enkephalin‐Arg‐Phe) raised in rabbits. The immunoreactivity was visualized by the peroxidase – antiperoxidase or immunofluorescence method. The light microscopic mirror method was applied to study the colocalization of F8Famide and NPY. The F8Famide‐immunoreactivity was concentrated in smaller areas of medial hypothalamus and nucleus of the solitary tract than that of enkephalins and NPY. In all brain areas, the distributions of F8Famide‐, enkephalin‐ and NPY‐immunoreactive neurons were distinct. F8Famide‐, NPY‐and enkephalin‐LI‐containing nerve terminals were seen in the nucleus of the solitary tract and in the lateral parabrachial nucleus. These results show that the neuronal systems containing F8Famide‐, enkephalin‐ or NPY‐LI are anatomically separate in all brain regions. However, there are terminal areas in which more than one type of these immunoreactivities are detected. These results have anatomical correlation with pharmacological reports, suggesting modulatory functions for these peptides on regulation of blood pressure, feeding behaviour and endocrine functions.
Projections from Areas 18 and 19 to Cat Striate Cortex: Divergence and Laminar Specificity
Authors: Henry G. H. , Salin P. A. , Bullier J.
Published: April 2006

The results of electrical stimulation experiments [Bullier et al., (1988) Exp. Brain Res., 70, 90–98] demonstrated that afferents from areas 18 and 19 contact different functional types of neurons in area 17. We were therefore interested in examining whether these results could be explained by differences in the morphology of the terminals of these two groups of afferent connections to area 17. We also wanted to confirm, by a direct method, our earlier results [Salin et al. (1989) J. Comp. Neurol., 283, 486–512] that cortical afferents to area 17 in the cat present extensive divergences. We therefore placed small injections of anterograde tracers in areas 18 and 19 and examined the laminar distributions of terminals thus revealed and the extent of the surface of area 17 contacted by these terminals. Three tracers were used: wheat germ agglutinin – horseradish peroxidase (WGA–HRP), Phaseolus vulgaris leucoagglutinin (Pha‐L) and biocytin. The results show that the divergence of these afferent connections are very extensive: 7–8 mm in the rotrocaudal direction and 3.5–6 mm in the mediolateral direction. In other words, neurons located in a region a few hundreds micron wide in areas 18 or 19 contact a region of area 17 covering several millimeters. Corticocortical connections are therefore not organized in a point‐to‐point fashion but are strongly divergent. The laminar distributions of terminals from areas 18 and 19 displayed a specific pattern. Area 19 projects most heavily to layers 5 and 6, also terminates in layers 1–3 and very little is present in layer 4. In contrast, the afferent terminals from area 18 are heaviest in layers 1, 2, 3, 4A and 5 and are rare in layer 6. Injections placed at different depths in area 18 revealed that upper layer neurons in that area mostly project to layers 1, 2, 3 and 5 in area 17, whereas lower layer neurons send their heaviest projections to layers 4A, 5 and 6 and hardly project to layers 1, 2 and 3.
On the Life Span of Olfactory Receptor Neurons
Authors: Mackay‐Sim A. , Kittel P. W.
Published: April 2006

The life span of olfactory receptor neurons was investigated after injection of a retrograde tracer into the olfactory bulb. Mice were injected unilaterally with colloidal gold conjugated with Concanavalin A and their olfactory epithelia were examined after 7, 14, 30, 60, and 90 days. Gold particles could be seen in the epithelia at all survival periods after silver intensification. There was no gold in the epithelia on the uninjected side. In order to test whether gold could be recycled within the epithelium upon the death of receptor neurons, the olfactory bulbs of some mice were ablated 4 days after colloidal gold injection. None of the receptor neurons in these epithelia contained gold at any survival period. To investigate whether gold was continuously available at the injection site, olfactory bulbs were examined by electron microscopy. By 7 days after injection all gold was sequestered intracellularly and was presumably unavailable for uptake by the olfactory axons. These results indicate that olfactory receptor neurons live for at least three times the commonly accepted life span of 30 days. A long life span challenges the widely held view that olfactory receptor neurons are regularly replaced.
Noradrenergic Control of Thalamic Oscillation: the Role of α‐2 Receptors
Authors: Buzsáki G. , Kennedy B. , Solt V. B. , Ziegler M.
Published: April 2006

The effects of α‐adrenergic drugs on neocortical high voltage spike and wave spindles (HVS), reflecting thalamic oscillation, was investigated in freely moving rats. HVS occurred spontaneously in the awake but immobile animal. Peripheral administration of the α‐1 antagonist, prazosin and α‐2 agonists, xylazine and clonidine increased the incidence and duration of HVS in a dose‐dependent manner. The α‐2 antagonist, yohimbine and the tricyclic antidepressants, desipramine and amitriptyline, significantly decreased the incidence of the neocortical HVS. Bilateral microinjections of the α‐2 agonists into the nucleus ventralis lateralis area of the thalamus, but not into the hippocampus or corpus callosum, was as effective as peripheral injection of these drugs. Xylazine was most effective in Fischer 344 rats that display high spontaneous rate of HVS and less effective in the Sprague – Dawley and Buffalo strains. The HVS‐promoting effect of clonidine was antagonized by prior intrathalamic injection of the α‐2 antagonist, yohimbine. The amplitude of the HVS was increased by picomole amounts of unilaterally‐injected clonidine. Neurotoxic destruction of the thalamopetal noradrenergic afferents by intracisternal or intrathalamic injection of 6‐hydroxydopamine, but not by peripheral administration of DSP‐4, increased the incidence of HVS. Importantly, intrathalamic administration of xylazine continued to induce HVS after destroying the thalamic noradrenergic terminals. Following downregulation of the α‐2 adrenoceptors by chronic administration (3 weeks) of amitriptylene the incidence of HVS decreased and the effectiveness of intrathalamic xylazine on the induction of HVS was significantly reduced. Based on these findings, we suggest that a major action of α‐2 adrenergic drugs on thalamic oscillation may be mediated by postsynaptic α‐2 adrenoceptors located on the thalamocortical neurons. We hypothesize that noradrenaline in the thalamus has a dual effect on the relay cells: blocking and promoting thalamic oscillation via α‐1 and α‐2 receptors, respectively. The final physiological effect is assumed to be a function of the relative density and affinity of these adrenergic receptor subtypes.
The Neural Cell Adhesion Molecule (N‐CAM) Modulates K+ Channels in Cultured Glial Precursor Cells
Authors: Sontheimer Harald , Kettenmann Helmut , Schachner Melitta , Trotter Jacqueline
Published: April 2006

Application of antibodies against the neural cell adhesion molecule (N‐CAM) to O4‐positive murine glial precursor cells in vitro results in a reduction of two distinct K+ currents measured using the whole cell patch clamp technique. Both the A‐type and delayed rectifier K+ currents are reduced in amplitude within a few minutes of the application of poly‐ or monoclonal antibodies against N‐CAM. This effect is not due to the binding of any antibody to the surface of the glial precursor cells because monoclonal antibody directed against the O4 surface antigen, or polyclonal antibodies directed against liver cell membranes (which also bind to the surface of glial precursor cells), do not affect membrane currents. Activators of protein kinase C, such as phorbol esters or diacylglycerol, also induce changes in potassium currents that appear, both in magnitude and kinetics, to be similar to those induced by antibodies against N‐CAM. In contrast, activation of G proteins upregulates K+ currents. Glial precursor cells thus respond to triggering of N‐CAM by altering channel properties. These observations suggest that adhesive events between neural cells can influence the intracellular ionic milieu.
Differential Distribution of Somatostatin‐like Immunoreactivity in the Visual Sector of the Thalamic Reticular Nucleus in Galago
Authors: Conley Michael , Schmechel Donald E. , Diamond Irving T.
Published: April 2006

Immunocytochemical methods were used to compare the distributions of somatostatin‐14 (SOM) and glutamic acid decarboxylase (GAD) in the medial and lateral tiers of the visual sector of the thalamic reticular nucleus in the bushbaby, Galago. As expected, all of the neurons in the visual sector were immunoreactive for GAD, the synthesizing enzyme for GABA, but the distribution of SOM‐immunoreactive cells was not uniform. It appeared that every cell in the medial tier was immunoreactive for SOM, but that very few cells in the lateral tier contained this neuropeptide. The significance of the difference in reticular neuron SOM content could be related to the functional differences between the dorsal lateral geniculate nucleus, which is connected reciprocally with the lateral tier, and the pulvinar nucleus, which is connected reciprocally with the medial tier.
Origins of Spinal Ascending Pathways that Reach Central Areas Involved in Visceroception and Visceronociception in the Rat
Authors: Menétrey D. , de Pommery J.
Published: April 2006

The location of spinal cells projecting rostrally to central areas that process visceroception and visceronociception were studied in rat using the retrograde transport of a protein‐gold complex. Origins of afferents to the nucleus tractus solitarius (the spinosolitary tract), the parabrachial area (the spinoparabrachial tract), the hypothalamus (the spinohypothalamic tract) and the amygdala (the spinoamygdalar tract) were studied at thoracic, lumbar and sacral levels, where spinal visceroceptive areas are concentrated. All of the afore‐mentioned pathways have common origins in the lateral spinal nucleus and in the reticular formation of the neck of the dorsal horn at all the levels studied, and also in the dorsal grey commissure and adjacent areas at sacral levels. The spinosolitary and the spinoparabrachial tracts are dense pathways, both of which are also characterized by afferents from the superficial layers of the dorsal horn at all the levels studied and from cells lying in close proximity to some autonomie spinal areas. These autonomie areas are the central autonomie nucleus (dorsal commissural nucleus) of lamina X at thoracolumbar levels and the parasympathetic column at sacral levels; some projections from the intermediolateral cell column at thoracic levels were also noted. Projections from all these autonomie structures to the parabrachial area have not yet been recognized. Thus, the origin of the spinoparabrachial tract closely resembles that of the spinomesencephalic tract that reaches the periaquaductal grey and adjacent areas. The spinohypothalamic and the spinoamygdalar tracts are smaller pathways. Direct spinal connections to the amygdala have not been reported previously. Both the hypothalamus and amygdala receive projections from lamina VII cells at low thoracic and upper lumbar levels in a pattern that resembles that of the preganglionic cells of the intercalated nucleus. Hypothalamic projections from the sacral parasympathetic area were also noted. The use of c‐fos as a functional marker to identify spinal neurons that are activated by noxious visceral stimulation suggests that both the spinoparabrachial and the spinosolitary tracts contribute significantly to the central transmission of visceronociceptive messages. Most of the visceronociceptive ascending projections in these pathways issued from lamina I cells. The results presented here confirm previous observations regarding the spinosolitary and the spinohypothalamic tracts and also demonstrate, for the first time, the complex origin of the spinoparabrachial tract and the existence of direct spinal afferents to the amygdala. These findings suggest that rostral transmission and central integration of visceral inputs require several parallel routes. The spinosolitary and spinoparabrachial tracts clearly play a role in conveying information regarding visceronociception.
Behavioural Correlates of the Release and Subsequent Action of Acetylcholinesterase Secreted in the Substantia Nigra
Authors: Jones S. A. , Greenfield S. A.
Published: April 2006

Acetylcholinesterase is secreted in the central nervous system (independently of cholinergic transmission) in a non‐classic, non‐enzymatic capacity. A light‐emitting reaction has recently been established that demonstrates release of this protein from the substantia nigra of a guinea pig with a temporal resolution corresponding to real time, i.e. ‘on‐line’. In this study the technique has been applied to investigate the significance of this novel phenomenon in the generation of specific types of movement. During locomotion a ‘pulsatile’ release of acetylcholinesterase occurs much more frequently than in other situations. However, these pulses of released acetylcholinesterase are of shorter duration than the respective periods of locomotion that caused them. Furthermore, as episodes of movement are repeated, the release of acetylcholinesterase becomes less likely. These observations suggest that the phenomenon does not simply reflect ongoing movement. Indeed, chewing behaviour is frequently initiated when acetylcholinesterase release occurs during locomotor activity. Hence, acetylcholinesterase released in association with locomotion may favour the onset of further types of movement.