bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ontogenetic development of the diencephalic MCH neurons: a hypothalamic ‘MCH area’ hypothesis
Authors: Brischoux F. , Fellmann D. , Risold P. Y. 
Published: March 2003

AbstractThe ontogeny of rat diencephalic melanin‐concentrating hormone (MCH) neurons has been analysed, using the bromodeoxyuridine method to determine the period of birth of these neurons, and using in situ hybridization and immunohistochemistry to study their chemical differentiation. The spatiotemporal pattern of MCH neuron generation is complex, although it is broadly lateromedial with a peak between embryonic days (E) 12 and E13. The first expression of the MCH gene has been detected on E13 in neurons in the presumptive lateral hypothalamic area. But the adult‐like pattern was observed from E18. Medial‐most MCH neurons express the peptide CART (cocaine‐amphetamine‐regulated transcript) from E18, and the receptor neurokinin 3 (NK3) from between postnatal day (P) 0 and P5. These results are discussed and compared with data from the literature to better understand the organization of the ‘MCH‐containing area’.
Glutamate receptor targeting in the postsynaptic spine involves mechanisms that are independent of myosin Va
Authors: Petralia Ronald S. , Wang Ya‐Xian , Sans Nathalie , Worley Paul F. , Hammer Iii John A. , Wenthold Robert J. 
Published: March 2003

AbstractTargeting of glutamate receptors (GluRs) to synapses involves rapid movement of intracellular receptors. This occurs in forms of synaptic upregulation of receptors, such as long‐term potentiation. Thus, many GluRs are retained in a cytoplasmic pool in dendrites, and are transported to synapses for upregulation, presumably via motor proteins such as myosins travelling along cytoskeletal elements that extend up into the spine. In this ultrastructural immunogold study of the cerebellar cortex, we compared synapses between normal rats/mice and dilute lethal mutant mice. These mutant mice lack myosin Va, which has been implicated in protein trafficking at synapses. The postsynaptic spine in the cerebellum lacks the inositol trisphosphate receptor (IP3R) ‐laden reticular tubules that are found in normal mice and rats (Takagishi et al., Neurosci. Lett., 1996, 215, 169). Thus, we tested the hypothesis that myosin Va is necessary for transport of GluRs and associated proteins to spine synapses. We found that these spines retain a normal distribution of (i) GluRs (delta 1/2, GluR2/3 and mGluR1α), (ii) at least one associated MAGUK (membrane‐associated guanylate kinase) protein, (iii) Homer (which interacts with mGluR1α and IP3Rs), (iv) the actin cytoskeleton, (v) the reticulum‐associated protein BiP, and (vi) the motor‐associated protein, dynein light chain. Thus, while myosin Va may maintain the IP3R‐laden reticulum in the spine for proper calcium regulation, other mechanisms must be involved in the delivery of GluRs and associated proteins to synapses. Other possible mechanisms include diffusion along the extrasynaptic membrane and delivery via other motors running along the spine's actin cytoskeleton.
Radial migration in the cerebral cortex is enhanced by signals from thalamus
Authors: Edgar Julia M. , Price David J. 
Published: March 2003

AbstractThe six layered cerebral cortex derives from cells that divide in the ventricular zone and migrate to their final destination in the cortical plate (future cortex). In the mouse, cortical layer III and IV neurons undergo their final mitotic division at around E16, at which time thalamic axons are beginning to enter the cortex. We used bromodeoxyuridine‐birthdating of cells in cortical slice cultures to show that the thalamus enhances the migration out of the ventricular zone of future layer III/IV cells. When cortical slices were cultured alone, less than 35% of cells born in vitro on E16 were present in the pial half of the slice after 48 h in culture. In contrast, when cortical slices were cocultured with thalamus, 69% of these cells were found in the pial half of the slice. Explants of other developing tissues did not mimic the effect of the thalamus. The thalamus had no obvious effect on cortical radial glial cells, cortical cell viability or maintenance of cortical slice structure. We found that most precursors born at a similar age but in vivo, shortly before cortical slices were isolated, migrated to the pial half of the cultured slices in the absence of a cocultured thalamic explant. Thus, E16 cortical slices cultured without thalamus permit migration of cells born in vivo and therefore already exposed to the thalamus. Our results indicate that the thalamus provides factors to E16‐born cortical precursors that enhance their directed migration out of the ventricular zone to the cortical plate.
Sensory enrichment after peripheral nerve injury restores cortical, not thalamic, receptive field organization
Authors: Florence S. L. , Boydston L. A. , Hackett T. A. , Lachoff H. Taub , Strata F. , Niblock M. M. 
Published: March 2003

AbstractSensory perception can be severely degraded after peripheral injuries that disrupt the functional organization of the sensory maps in somatosensory cortex, even after nerve regeneration has occurred. Rehabilitation involving sensory retraining can improve perceptual function, presumably through plasticity mechanisms in the somatosensory processing network. However, virtually nothing is known about the effects of rehabilitation strategies on brain organization, or where the effects are mediated. In this study, five macaque monkeys received months of enriched sensory experience after median nerve cut and repair early in life. Subsequently, the sensory representation of the hand in primary somatosensory cortex was mapped using multiunit microelectrodes. Additionally, the primary somatosensory relay in the thalamus, the ventroposterior nucleus, was studied to determine whether the effects of the enrichment were initiated subcortically or cortically. Age‐matched controls included six monkeys with no sensory manipulation after median nerve cut and regeneration, and one monkey that had restricted sensory experience after the injury. The most substantial effect of the sensory environment was on receptive field sizes in cortical area 3b. Significantly greater proportions of cortical receptive fields in the enriched monkeys were small and well localized compared to the controls, which showed higher proportions of abnormally large or disorganized fields. The refinements in receptive field size and extent in somatosensory cortex likely provide better resolution in the sensory map and may explain the improved functional outcomes after rehabilitation in humans.
Electrophysiological characterization of laminar synaptic inputs to the olfactory tubercle of the rat studied in vitro: modulation of glutamatergic transmission by cholinergic agents is pathway‐specific
Authors: Owen G. S. , Halliwell J. V. 
Published: March 2003

AbstractWe have exploited the complementary arrangement of afferents in a coronal slice (300–400 µm) of the rat olfactory tubercle (OT) maintained in vitro to investigate transmission in two separate synaptic pathways. We recorded extracellular responses within the OT dense cell layer in slices and stimulated either the outermost layer to activate primary olfactory fibres or deeper to activate secondary input. Superficial stimulation produced a synaptic potential with superimposed population spike. This interpretation was based on blockade by calcium removal from the bathing medium and the use of the glutamate antagonist DNQX (10 µm); the spike was found to be selectively suppressed by tetrodotoxin applied near the cells. The spike, but not the synaptic wave, was depressed by 12 mm Ca2+ and enhanced by 1 mm Ba2+ in the bathing medium. Deep stimulation to activate association and intrinsic fibres elicited a nerve volley followed by a later response, also blocked by Ca2+ removal or 10 µm DNQX. It was unaffected by high Ca2+ or Ba2+, hence resulting from synaptic and not action current flow. Removal of Mg2+ from the bathing medium revealed an NMDA component of synaptic transmission at both loci that was selectively blocked by D‐AP‐5. The deep synaptic response, only, was depressed by carbachol IC50 7 µm or muscarine IC50 13 µm. This depression was also induced by AChE inhibitors eserine or tacrine and was antagonized by 1 µm atropine or 5–10 µm clozapine. These results characterize transmission in the OT and demonstrate a role for muscarinic modulation of deeper synapses in the OT that is influenced by psychotherapeutic drugs.
Modulation of dendrodendritic interactions and mitral cell excitability in the mouse accessory olfactory bulb by vaginocervical stimulation
Authors: Otsuka Tomoko , Ishii Keiji , Osako Yoji , Okutani Fumino , Taniguchi Mutsuo , Oka Tatsuzo , Kaba Hideto 
Published: March 2003

AbstractWhen female mice are mated, they form a memory to the pheromonal signal of their male partner. The neural changes underlying this memory occur in the accessory olfactory bulb, depend upon vaginocervical stimulation at mating and involve changes at the reciprocal synapses between mitral and granule cells. However, the action of vaginocervical stimulation on the reciprocal interactions between mitral and granule cells remains to be elucidated. We have examined the effects of vaginocervical stimulation on paired‐pulse depression of amygdala‐evoked field potentials recorded in the external plexiform layer of the accessory olfactory bulb (AOB) and the single‐unit activity of mitral cells antidromically stimulated from the amygdala in urethane‐anaesthetized female mice. Artificial vaginocervical stimulation reduced paired‐pulse depression (considered to be due to feedback inhibition of the mitral cell dendrites from the granule cells via reciprocal dendrodendritic synapses) recorded in the AOB external plexiform layer. As would be expected from this result, vaginocervical stimulation also enhanced the spontaneous activity of a proportion of the mitral cells tested. These results suggest that vaginocervical stimulation reduces dendrodendritic feedback inhibition to mitral cells and enhances their activity.
Δ9‐tetrahydrocannabinol releases and facilitates the effects of endogenous enkephalins: reduction in morphine withdrawal syndrome without change in rewarding effect
Authors: Valverde Olga , Noble Florence , Beslot Françoise , Daugé Valérie , Fournié‐Zaluski Marie‐Claude , Roques Bernard P. 
Published: March 2003

AbstractRecent studies have suggested that cannabinoids might initiate the consumption of other highly addictive substances, such as opiates. In this work, we show that acute administration of Δ9‐tetrahydrocannabinol in mice facilitates the antinociceptive and antidepressant‐like responses elicited by the endogenous enkephalins protected from their degradation by RB 101, a complete inhibitor of enkephalin catabolism. This emphasizes the existence of a physiological interaction between endogenous opioid and cannabinoid systems. Accordingly, Δ9‐tetrahydrocannabinol increased the release of Met‐enkephalin‐like material in the nucleus accumbens of awake and freely moving rats measured by microdialysis. In addition, this cannabinoid agonist displaced the in vivo[3H]diprenorphine binding to opioid receptors in total mouse brain. The repetitive pretreatment during 3 weeks of Δ9‐tetrahydrocannabinol in mice treated chronically with morphine significantly reduces the naloxone‐induced withdrawal syndrome. However, this repetitive administration of Δ9‐tetrahydrocannabinol did not modify or even decrease the rewarding responses produced by morphine in the place preference paradigm. Taken together, these behavioural and biochemical results demonstrate the existence of a direct link between endogenous opioid and cannabinoid systems. However, chronic use of high doses of cannabinoids does not seem to potentiate the psychic dependence to opioids.
Glutamate transporter expression in astrocytes of the rat dentate gyrus following lesion of the entorhinal cortex
Authors: Hein C. , Horváth E. , Kugler P. 
Published: March 2003

AbstractThe glutamate transporters GLT‐1 and GLAST localized in astrocytes are essential in limiting transmitter signalling and restricting harmful receptor overstimulation. To show changes in the expression of both transporters following lesion of the entorhinal cortex (and degeneration of the glutamatergic tractus perforans), quantitative microscopic in situ hybridization (ISH) using alkaline‐phosphatase‐labelled oligonucleotide probes was applied to the outer molecular layer of the hippocampal dentate gyrus of rats (termination field of the tractus perforans). Four groups of rats were studied: sham‐operated controls, and animals 3, 14 and 60 days following unilateral electrolytic lesion of the entorhinal cortex. The postlesional shrinkage of the terminal field of the perforant path, ipsilateral to the lesion side, was determined and considered in the evaluation of quantitative ISH data. Statistical analysis revealed that ipsilateral to the lesion side there was a significant decrease of the GLT‐1 mRNA at every postlesional time‐point and of the GLAST mRNA at 14 and 60 days postlesion. The maximal decrease was ≈ 45% for GLT‐1 and ≈ 35% for GLAST. In the terminal field of the perforant path contralateral to the lesion side, no significant changes of ISH labelling were measured. The results were complemented by immunocytochemical data achieved using antibodies against synthetic GLT‐1 and GLAST peptides. In accordance with ISH results, there was an obvious decrease of GLT‐1 and GLAST immunostaining in the terminal field of the perforant path ipsilateral to the lesion side. From these data we conclude that, following a lesioning of the entorhinal cortex, the loss of glutamatergic synapses in the terminal field of the perforant path resulted in a strong downregulation of glutamate transporters in astrocytes. The decrease of synaptically released glutamate or of other neuronal factors could be involved in this downregulation.
Neurotoxicity of channel mutations in heterologously expressed α7‐nicotinic acetylcholine receptors
Authors: Lukas Ronald J. , Lucero Linda , Buisson Bruno , Galzi Jean‐Luc , Puchacz Elzbieta , Fryer John D. , Changeux Jean‐Pierre , Bertrand Daniel 
Published: March 2003

AbstractNicotinic acetylcholine receptors (nAChR) composed of chick α7 subunits mutated to threonine at amino acid valine‐251 in the putative channel‐lining M2 domain were expressed heterologously in several neuron‐like and non‐neuronal mammalian cell lines. Expression of mutant α7‐nAChR is toxic to neuron‐like cells of the human neuroblastoma cell lines SH‐SY5Y and IMR‐32, but not to several other cell types. Growth in the presence of the α7‐nAChR antagonist methyllycaconitine (MLA) protects against neurotoxicity, as does gradual downregulation of functional, mutant α7‐nAChR in surviving transfected SH‐SY5Y cells. Relative to wild‐type α7‐nAChR, functional α7‐nAChR mutants show a higher affinity for agonists, slower rates of desensitization, and sensitivity to dihydro‐β‐erythroidine (DHβE) as an agonist, but they retain sensitivity to MLA as a competitive antagonist. These findings demonstrate that expression of hyperfunctional, mutant forms of Ca2+‐permeable α7‐nAChR is toxic to neuron‐like cells.
Opposing effects of behavioural activity and light on neurons of the suprachiasmatic nucleus
Authors: Schaap Jeroen , Meijer Johanna H. 
Published: March 2003

AbstractThe mammalian circadian pacemaker is located in the suprachiasmatic nuclei. It can be shifted in phase by photic cues and by the behavioural activity of the animal. When presented together, light and behavioural activity attenuate each others' phase‐shifting effect. Still unclear is how behavioural activity affects the suprachiasmatic nuclei and how it interacts with photic information. Previously, we reported the occurrence of behaviourally induced suppressions of neuronal activity. The present study investigates the characteristics of these suppressions as a function of circadian time and, additionally, in the presence of photic cues. We performed long‐term multiunit activity recordings of neurons in freely moving rats and found that these suppressions of neuronal firing in the suprachiasmatic nucleus occurred at every phase of the circadian cycle. The magnitude of the suppressions showed a circadian variation, with larger suppressions during subjective day. When a light pulse was applied during a suppression, light and activity appeared to oppose each others' effects within the recorded population of neurons. The resulting discharge level appeared to be the sum of both responses. The opposing effects of light and activity were also found in single unit recordings, indicating that photic and behavioural stimuli interact at the level of a single neuron.
Lesions of the pedunculopontine tegmental nucleus reduce paradoxical sleep (PS) propensity: evidence from a short‐term PS deprivation study in rats
Authors: Deurveilher Samuel , Hennevin Elizabeth 
Published: March 2003

AbstractCholinergic neurons in the mesopontine tegmentum are thought to play a critical role in the generation of paradoxical sleep (PS). However, no study has yet examined whether lesions of these neurons cause deficits of PS in the rat. We describe here the effects of lesions of the pedunculopontine tegmental nucleus (PPT) on spontaneous PS and on PS propensity, expressed during and after a short period of PS deprivation. Lesions were induced by bilateral injections of ibotenate. PS deprivation was performed manually by gently waking rats each time they showed polygraphic signs of PS. Two weeks after lesions, an 8‐h baseline recording was performed; the following day, rats were PS deprived for 6 h and polygraphic recordings were then continued for 2 h, to examine recovery sleep. The same protocol was repeated 1 week later. Compared with controls and with rats with limited PPT lesions, rats bearing > 60% NADPH‐diaphorase‐positive cell loss within the PPT showed unaffected PS under baseline conditions. However, they made fewer attempts to enter PS during deprivation and they exhibited an attenuated rebound increase in PS time after deprivation. The number of PS attempts and the magnitude of PS rebound were negatively correlated with the percent loss of diaphorase‐positive neurons within the PPT. Thus, PS propensity that accumulated as a result of PS deprivation was reduced after extensive PPT lesions. In summary, although spontaneous PS was found to be unaltered, the PS deprivation procedure used in this study demonstrated the dysfunctioning of PS caused by PPT lesions.
Protective effect of harmaline and harmalol against dopamine‐ and 6‐hydroxydopamine‐induced oxidative damage of brain mitochondria and synaptosomes, and viability loss of PC12 cells
Authors: Kim Dong Hyun , Jang Yoon Young , Han Eun Sook , Lee Chung Soo 
Published: March 2003

AbstractThe present study elucidated the protective effect of β‐carbolines (harmaline, harmalol and harmine) against oxidative damage of brain mitochondria, synaptosomes and PC12 cells induced by either dopamine or 6‐hydroxydopamine. Harmaline, harmalol and antioxidant enzymes (superoxide dismutase/SOD and catalase) decreased the alteration of mitochondrial swelling and membrane potential induced by 200 µm dopamine or 100 µm 6‐hydroxydopamine. Deprenyl attenuated the dopamine‐induced mitochondrial dysfunction but did not reduce the effect of 6‐hydroxydopamine. While β‐carbolines inhibited the electron flow in mitochondria, they did not enhance the depressant effect of catecholamines. β‐Carbolines and antioxidant enzymes reversed the depression of synaptosomal Ca2+ uptake induced by 10 µm catecholamines. The compounds inhibited the catecholamine‐induced thioredoxin reductase inhibition, thiol oxidation and carbonyl formation in mitochondria and synaptosomes. β‐Carbolines decreased the reactive species‐induced deoxyribose degradation. Harmaline and harmalol reduced the catecholamine‐induced loss of the transmembrane potential and of cell viability in PC12 cells.β‐Carbolines alone did not show a significant cytotoxic effect on PC12 cells. The results suggest that β‐carbolines may attenuate the dopamine‐ or 6‐hydroxydopamine‐induced alteration of brain mitochondrial and synaptosomal functions, and viability loss in PC12 cells, by a scavenging action on reactive oxygen species and inhibition of thiol oxidation.
Patterned cerebellar Purkinje cell death in a transgenic mouse model of Niemann Pick type A/B disease
Authors: Sarna Justyna , Miranda Silvia R. P. , Schuchman Edward H. , Hawkes Richard 
Published: March 2003

AbstractNiemann Pick disease is a family of autosomal recessive disorders characterized by cholesterol accumulation. The most common type is Niemann Pick type A/B (NPA/B), resulting from deficient acid sphingomyelinase activity, which leads to sphingomyelin and cholesterol accumulation. The neuropathology of NPA/B includes widespread neuronal degeneration. An acid sphingomyelinase knockout mouse model of NPA/B (ASMKO) has been developed by the targeted deletion of the acid sphingomyelinase gene. When cerebellar morphology was examined in the ASMKO mouse at postnatal day 60 (P60), a dramatic pattern of longitudinal stripes was revealed in which roughly half the Purkinje cells had died, leaving a highly stereotyped, bilaterally symmetrical array of stripes. Antizebrin II immunocytochemistry revealed that the absent Purkinje cells corresponded exactly to the zebrin II‐negative subset, leaving the zebrin II‐positive subset apparently intact. By P120, some of the zebrin II‐positive Purkinje cells had also been eliminated from the posterior vermis and hemispheres. By P180, all Purkinje cells had been lost from the anterior lobe. Finally at P240, almost all Purkinje cells had disappeared to leave a stereotyped distribution in lobules VI, IX–X and the flocculus and paraflocculus. The temporal pattern of Purkinje cell death demonstrates differential susceptibility of morphologically identical cells that appear to be linked to their molecular phenotypes.
Identification of a cis‐acting dendritic targeting element in the mRNA encoding the alpha subunit of Ca2+/calmodulin‐dependent protein kinase II
Authors: Blichenberg Arne , Rehbein Monika , Müller Reinhold , Garner Craig C. , Richter Dietmar , Kindler Stefan 
Published: March 2003

AbstractIn mammalian neurons a selected group of mRNAs, including the transcript encoding the alpha subunit of Ca2+/calmodulin‐dependent protein kinase II, is found in dendrites. The molecular mechanisms underlying extrasomatic RNA trafficking are not well described. It is thought that dendritic transcripts contain cis‐acting elements that direct their selective subcellular sorting. Here we report the identification of an extrasomatic targeting element in the 3′ untranslated region of the mRNA encoding the alpha subunit of Ca2+/calmodulin‐dependent protein kinase II. In primary hippocampal neurons, this 1200‐nucleotide‐spanning, cis‐acting element is sufficient to mediate dendritic localization of chimeric reporter transcripts. The trafficking signal does not share any striking sequence similarity with a previously characterized dendritic targeting element in transcripts encoding the microtubule‐associated protein 2. In dendrites of transfected primary neurons, recombinant RNAs form granules with an average diameter of 0.45 µm that may represent preferential RNA docking sites or multimolecular transport units. These findings imply that extrasomatic sorting of individual dendritic mRNAs involves at least partially distinct molecular mechanisms, as well as large trafficking complexes.