bluuebunny/crossref_metadata_2025_split huggingface dataset:
Control of neurotransmission, behaviour and development, by photo‐dynamic manipulation of tissue redox state of brain targets
Authors: Kataoka Yosky , Morii Hiroshi , Imamura Kazuyuki , Cui Yilong , Kobayashi Masayuki , Watanabe Yasuyoshi 
Published: March 2003

AbstractReversible manipulation of local neurotransmission in brain areas, using controlled spatial and temporal resolution, is one of the powerful techniques used to investigate integrative aspects of brain function. We have developed a novel technique for rapidly inactivating local synaptic transmission, from outside the brain, within seconds or minutes via oxidation of target tissue using a photosensitive dye followed by photoirradiation (photo‐dynamic tissue oxidation; PDTO). PDTO applied through a defined slit, sharply suppressed excitatory synaptic transmission in rat hippocampal slices and also suppressed in vivo hippocampal neurotransmission reversibly. Furthermore, we manipulated the voluntary movement of gerbils in free‐field activity by application of PDTO to the striatum. Also, in freely moving kittens, the development of the visual cortex was manipulated by long‐lasting application of PDTO to the eye. Thus, PDTO enables external manipulation of in vivo or in vitro neurotransmission in various clearly defined regions on the submillimeter scale. Suppression of neurotransmission occurred only within the photo‐oxidized area which can be histochemically visualized.
The vagus nerve mediates behavioural depression, but not fever, in response to peripheral immune signals; a functional anatomical analysis
Authors: Konsman Jan Pieter , Luheshi Giamal N. , Bluthé Rose‐Marie , Dantzer Robert 
Published: March 2003

AbstractCytokines act on the brain to induce fever and behavioural depression after infection. Although several mechanisms of cytokine‐to‐brain communication have been proposed, their physiological significance is unclear. We propose that behavioural depression is mediated by the vagus nerve activating limbic structures, while fever would primarily be due to humoral mechanisms affecting the preoptic area, including interleukin‐6 (IL‐6) action on the organum vasculosum of the laminae terminalis (OVLT) and induction of prostaglandins. This study assessed the effects of subdiaphragmatic vagotomy in rats on fever, behavioural depression, as measured by the social interaction test, and Fos expression in the brain. These responses were compared with induction of the prostaglandin‐producing enzyme cyclooxygenase‐2 and the transcription factor Stat3 that translocates after binding of IL‐6. Vagotomy blocked behavioural depression after intraperitoneal injection of recombinant rat IL‐1β (25 µg/kg) or lipopolysaccharide (250 µg/kg; LPS) and prevented Fos expression in limbic structures and ventromedial preoptic area, but not in the OVLT. Fever was not affected by vagotomy, but associated with translocation of Stat3 in the OVLT and cyclooxygenase‐2 induction around blood vessels. These results indicate that the recently proposed vagal link between the immune system and the brain activates limbic structures to induce behavioural depression after abdominal inflammation. Although the vagus might play a role in fever in response to low doses of LPS by activating the ventromedial preoptic area, it is likely to be overridden during more severe infection by action of circulating IL‐6 on the OVLT or prostaglandins induced along blood vessels of the preoptic area.
Differential DNA damage in response to the neonatal and adult excitotoxic hippocampal lesion in rats
Authors: Khaing Zin Z. , Weickert Cynthia Shannon , Weinberger Daniel R. , Lipska Barbara K. 
Published: March 2003

AbstractWe examined the developmental profile of excitotoxin‐induced nuclear DNA fragmentation using the transferase dUTP nick‐end labelling (TUNEL) technique, as a marker of DNA damage and cell death in rats with neonatal and adult excitotoxic lesions of the ventral hippocampus. We hypothesized that infusion of neurotoxin may result in a differential pattern of cell death in neonatally and adult lesioned rats, both in the infusion site and in remote brain regions presumably involved in mediating behavioural changes observed in these animals. Brains of rats lesioned at 7 days of age and in adulthood were collected at several survival times 1–21 days after the lesion. In the lesioned neonates 1–3 days postlesion, marked increases in TUNEL‐positive cells occurred in the ventral hippocampus, the site of neurotoxin infusion, and in a wide surrounding area. Adult lesioned brains showed more positive cells than controls only at the infusion site. In the lesioned neonates, TUNEL‐labelled cells were also present in the striatum and nucleus accumbens 1 day postlesion but not at later survival times. Our findings indicate that cell death in remote regions is more prominent in immature than adult brains, that it may lead to distinct alterations in development of these brain regions, and thus may be responsible for functional differences between neonatally and adult lesioned rats.
Differential maturation of motoneurons innervating ankle flexor and extensor muscles in the neonatal rat
Authors: Vinay L , Brocard F. , Clarac F. 
Published: March 2003

AbstractThe first postnatal week is a critical period for the development of posture in the rat. The use of ankle extensor muscles in postural reactions increases during this period. Changes in excitability of motoneurons are probably an important factor underlying this maturation. The aim of this study was to identify whether variations in the maturation exist between motor pools innervating antagonistic muscles. Intracellular recordings in the in vitro brain stem–spinal cord preparation of neonatal rats (from postnatal day 0–5) were used to examine the developmental changes in excitability of motoneurons innervating the ankle flexors (F‐MNs) and the antigravity ankle extensors (E‐MNs). No significant difference in resting potential, action potential threshold, input resistance or rheobase was observed at birth. The age‐related increase in rheobase was more pronounced for F‐MNs than for E‐MNs. The development of discharge properties of E‐MNs lagged behind that of F‐MNs. More F‐MNs than E‐MNs were able to fire repetitively in response to current injection at birth. F‐MNs discharged at a higher frequency than E‐MNs at all ages. Differences in the duration of action potential afterhyperpolarization accounted, at least partly, for the differences in discharge frequency between E‐MNs and F‐MNs at birth, and for the age‐related increase in firing rate. These results suggest that E‐MNs are more immature at birth than F‐MNs and that there is a differential development of motoneurons innervating antagonistic muscles. This may be a critical factor in the development of posture and locomotion.
Retrograde signalling with nitric oxide at neocortical synapses
Authors: Volgushev Maxim , Balaban Pavel , Chistiakova Marina , Eysel Ulf T. 
Published: March 2003

AbstractLong‐term changes of synaptic transmission in slices of rat visual cortex were induced by intracellular tetanization: bursts of short depolarizing pulses applied through the intracellular electrode without concomitant presynaptic stimulation. Long‐term synaptic changes after this purely postsynaptic induction were associated with alterations of release indices, thus providing a case for retrograde signalling at neocortical synapses. Both long‐term potentiation and long‐term depression were accompanied by presynaptic changes, indicating that retrograde signalling can achieve both up‐ and down‐regulation of transmitter release. The direction and the magnitude of the amplitude changes induced by a prolonged intracellular tetanization depended on the initial properties of the input. The inputs with initially high paired‐pulse facilitation (PPF) ratio, indicative of low release probability, were most often potentiated. The inputs with initially low PPF ratio, indicative of high release probability, were usually depressed or did not change. Thus, prolonged postsynaptic activity can lead to normalization of the weights of nonactivated synapses. The dependence of polarity of synaptic modifications on initial PPF disappeared when plastic changes were induced with a shorter intracellular tetanization, or when the NO signalling pathway was interrupted by inhibition of NO synthase activity or by application of NO scavengers. This indicates that the NO‐dependent retrograde signalling system has a relatively high activation threshold. Long‐term synaptic modifications, induced by a weak postsynaptic challenge or under blockade of NO signalling, were nevertheless associated with presynaptic changes. This suggests the existence of another retrograde signalling system, additional to the high threshold, NO‐dependent system. Therefore, our data provide a clear case for retrograde signalling at neocortical synapses and indicate that multiple retrograde signalling systems, part of which are NO‐dependent, are involved.
Effects of selective excitotoxic prefrontal lesions on acquisition of nonmatching‐ and matching‐to‐place in the T‐maze in the rat: differential involvement of the prelimbic–infralimbic and anterior cingulate cortices in providing behavioural flexibility
Authors: Dias R. , Aggleton J. P. 
Published: March 2003

AbstractThe present study investigated the contributions of the medial prefrontal cortex and its major subdivisions, the dorsal anterior cingulate (ACd) and prelimbic–infralimbic (PL) cortices, to spatial working memory and inhibitory control processes. In experiment 1, excitotoxic lesions centred in the ACd or PL cortex did not affect acquisition of a nonmatching‐to‐place task in the T‐maze with a retention interval of 10 s. However, the same reinforced alternation task was impaired by larger prefrontal lesions that combined ACd and PL cortices. In experiment 2, new animals were trained on a matching‐to‐place task in the T‐maze that uses a rule counter to the animals' innate bias to alternate spontaneously. Now, discrete lesions of both the ACd and PL cortices impaired acquisition, but in different ways. Both animals with PL and with ACd lesions perseverated by nonmatching for more sessions than the controls, but only the PL animals also showed a more general increase in perseveration reflected in a further, extended period of applying an inefficient response rule (e.g. always turn right) and a deficit at reversing from matching to nonmatching. Acquisition of the matching‐to‐place task was also impaired by combined lesions of ACd and PL cortices. Overall, whilst spatial working memory processes appear to remain intact in those animals with discrete prefrontal lesions, the present findings provide strong evidence for the differential involvement of the prelimbic–infralimbic and anterior cingulate regions in providing behavioural flexibility.
Differential adrenergic regulation of the circadian expression of the clock genes Period1 and Period2 in the rat pineal gland
Authors: Takekida Seiichi , Yan Lily , Maywood Elizabeth S. , Hastings Michael H. , Okamura Hitoshi 
Published: March 2003

AbstractPrecise temporal regulation of transcription is pivotal to the role of the mammalian pineal gland as a transducer of circadian and seasonal information. The circadian clock genes Per1 and Per2 encode factors implicated in temporally gated transcriptional programmes in brain and pituitary. Here we show that the nocturnal circadian expression of Per1 and Per2 in the rat pineal gland parallels that of serotonin N‐acetyltransferase (NAT) mRNA, which encodes the rate‐limiting enzyme of melatonin biosynthesis. This rhythm is dependent upon an intact sympathetic innervation. Increases in rPer1 (r indicates rat) and rPer2, as well as rNAT, expression during subjective night were blocked completely by superior cervical ganglionectomy (SCGX). In SCGX rats, the β‐adrenergic receptor agonist isoproterenol rapidly induced the rPer1 mRNA with dynamics very similar to its effect on rNAT mRNA. In contrast, isoproterenol was without effect on expression of rPer2 mRNA. These findings demonstrate that circadian pineal expression of both rPer1 and rPer2 is controlled by sympathetic afferent innervation, but whereas β‐adrenergic signalling regulates rPer1 and rNAT, an alternative route mediates sympathetic regulation over rPer2 expression.
Increased expression of neuronal nitric oxide synthase mRNA in the accessory olfactory bulb during the formation of olfactory recognition memory in mice
Authors: Okere Chuma O. , Kaba Hideto 
Published: March 2003

AbstractThe mouse accessory olfactory bulb contains a high density of nitric oxide synthase and, in females, is involved in the formation of a mating and pheromone‐specific recognition memory. The exact role of nitric oxide in this memory model is not yet clearly understood. In this study, in situ hybridization was used to assess neuronal nitric oxide synthase mRNA expression during the critical interval associated with synaptic plasticity in the accessory olfactory bulb of female mice leading to the formation of a recognition memory for the stud male pheromones present following mating. Nitric oxide synthase mRNA was significantly increased following mating and 120‐min stud male exposure compared with oestrus mice. The mRNA expression was more predominant in the anterior than the posterior regions of the bulb. These observations indicate a stimulus‐specific activation of nitric oxide gene expression in the female mouse accessory olfactory bulb and support the hypothesis that nitric oxide may modulate intermediate synaptic pathways during the formation of a pheromone‐dependent olfactory recognition for stud males.
Vascular endothelial growth factor is a neurotrophic factor which stimulates axonal outgrowth through the flk‐1 receptor
Authors: Sondell Mariann , Sundler Frank , Kanje Martin 
Published: March 2003

AbstractVascular endothelial growth factor (VEGF) is an angiogenic factor that stimulates axonal outgrowth. Here we used in situ hybridization and immunocytochemistry to study the VEGF receptor flk‐1 in cultured superior cervical ganglia (SCG) and dorsal root ganglia (DRG) from adult mice, and also the effects of VEGF on regeneration in vitro. Neurons in both ganglia contained the flk‐1 receptor and showed an increased mRNA expression and immunoreactivity for flk‐1 after 48 h in culture. In SCG, but not in DRG, double immunostaining for flk‐1 and VEGF revealed coexpression in many neurons, implying that VEGF may exert both autocrine and paracrine actions. One proportion of the flk‐1‐positive neurons in DRG stained positive for the large neuron marker RT97 and another proportion expressed calcitonin gene‐related peptide (CGRP). Small IB4‐positive neurons were devoid of flk‐1 immunoreactivity. Most flk‐1‐positive neurons in the DRG, but not in the SCG, were also immunoreactive to neuropilin‐1. VEGF was found to stimulate axonal outgrowth from DRG, both by an action on the growing axons and the nerve cell bodies. The latter effect could be mediated by retrograde axonal transport as revealed by the use of a two compartment system to assay axonal outgrowth. We also found that the VEGF‐induced axonal outgrowth was blocked by the flk‐1 inhibitor SU5416. The results strongly suggest that VEGF acts as a neurotrophic factor and plays an important role during the regeneration of peripheral nerves.
The central acoustic tract and audio‐vocal coupling in the horseshoe bat, Rhinolophus rouxi
Authors: Behrend O. , Schuller G. 
Published: March 2003

AbstractDoppler shift compensation (DSC) behaviour in horseshoe bats is a remarkable example of sensorimotor feedback that stabilizes the echo frequency at the bat's optimum hearing range regardless of motion‐induced frequency shifts in the echoes. Searching for a related neural interface, the nucleus of the central acoustic tract (NCAT) was investigated in the echolocating horseshoe bat, Rhinolophus rouxi, using various neurophysiological and tracer methods. The NCAT receives bilateral auditory input from the cochlear nuclei and sends projections to regions outside the classical acoustic pathway like the pretectal area or the superior colliculus. The binaural input is excitatory from the contralateral and inhibitory from the ipsilateral ear to 53% of the units, and auditory responses were biased to frontal and contralateral directions. The best frequencies of NCAT neurons match a narrow range above the main frequency component of the bat's species‐specific echolocation call (62% of the units), and the neurons exhibit extremely sharp tuning (Q10dB up to 632). DSC is degraded by unilateral electrical or pharmacological microstimulation of the NCAT, and heavily impaired by unilateral lesion of the region. Altogether, the efferents of the NCAT to prevocal areas, the tuning of its neurons to the DSC‐relevant echo frequency range, and the possibility to affect DSC by manipulation of the NCAT, support the assumption that the nucleus plays an important role in audio‐vocal control in the horseshoe bat.
Cooperative changes in GABA, glutamate and activity levels: the missing link in cortical plasticity
Authors: Arckens Lutgarde , Schweigart Georg , Qu Ying , Wouters Griet , Pow D. V. , Vandesande Frans , Eysel Ulf T. , Orban Guy A. 
Published: March 2003

AbstractDifferent intracortical mechanisms have been reported to contribute to the substantial topographic reorganization of the mammalian primary visual cortex in response to matching lesions in the two retinas: an immediate expansion of receptive fields followed by a gradual shift of excitability into the deprived area and finally axonal sprouting of laterally projecting neurons months after the lesion. To gain insight into the molecular mechanisms of this adult plasticity, we used immunocytochemical and bioanalytical methods to measure the glutamate and GABA neurotransmitter levels in the visual cortex of adult cats with binocular central retinal lesions. Two to four weeks after the lesions, glutamate immunoreactivity was decreased in sensory‐deprived cortex as confirmed by HPLC analysis of the glutamate concentration. Within three months normal glutamate immunoreactivity was restored. In addition, the edge of the unresponsive cortex was characterized by markedly increased glutamate immunoreactivity 2–12 weeks postlesion. This glutamate immunoreactivity peak moved into the deprived area over time. These glutamate changes corresponded to decreased spontaneous and visually driven activity in unresponsive cortex and to strikingly increased neuronal activity at the border of this cortical zone. Furthermore, the previously reported decrease in glutamic acid decarboxylase immunoreactivity was found to reflect decreased GABA levels in sensory‐deprived cortex. Increased glutamate concentrations and neuronal activity, and decreased GABA concentrations, may be related to changes in synaptic efficiency and could represent a mechanism underlying the retinotopic reorganization that occurs well after the immediate receptive field expansion but long before the late axonal sprouting.
Up‐regulation of growth‐associated protein 43 mRNA in rat medial septum neurons axotomized by fimbria‐fornix transection
Authors: Haas Carola A. , Hollerbach Ewald , Deller Thomas , Naumann Thomas , Frotscher Michael 
Published: March 2003

AbstractTransection of septohippocampal fibres is widely used to study the response of CNS neurons to axotomy. Septohippocampal projection neurons survive axotomy and selectively up‐regulate the transcription factor c‐Jun. In the present study we investigated whether these cells concomitantly up‐regulate the growth‐associated protein‐43 (GAP‐43), a potential target gene of c‐Jun implicated in axonal growth and regeneration. Using in situ hybridization histochemistry (ISHH) it was demonstrated that postlesional c‐jun mRNA expression is accompanied by an increased expression of GAP‐43 mRNA in the medial septum 3 days following fimbria‐fornix transection (FFT). The increase reached a maximum at 7 days and gradually declined thereafter (17 days, 3 weeks). Retrograde prelabeling with Fluoro‐Gold followed by axotomy and ISHH revealed that GAP‐43 mRNA was up‐regulated in septohippocampal projection neurons. Colocalization of GAP‐43 mRNA and choline acetyltransferase protein showed that GAP‐43 mRNA was expressed by cholinergic medial septal neurons after axotomy. Selective immunolesioning of the cholinergic component of the septohippocampal projection with 192 IgG‐saporin followed by FFT demonstrated that GAP‐43 mRNA was also synthesized by axotomized GABAergic neurons. These results demonstrate an up‐regulation of GAP‐43 mRNA in axotomized septohippocampal projection neurons independent of their transmitter phenotype which is closely correlated with c‐Jun expression. Because the GAP‐43 gene contains an AP‐1 site, we hypothesize a c‐Jun‐driven up‐regulation of GAP‐43 in lesioned medial septal neurons that may contribute to their survival and regenerative potential following axotomy.
Migrating neurons cross a reelin‐rich territory to form an organized tissue out of embryonic cortical slices
Authors: Hedin‐Pereira Cecilia , DeMoraes Elizabeth C. P. , Santiago Marcelo F. , Méndez‐Otero Rosalia , Lent Roberto 
Published: March 2003

AbstractIn this study we show that the radial migration of neuronal precursors out of cerebral cortex of embryonic brain slices cultured for 4–7 days gives rise to an organized tissue that forms de novo off developing slices. In our in vitro preparations, migrating neuronal precursors overshot the marginal zone, as did the elongation of radial glial processes out of the slices. These cells detached from radial glia at a distance from the cortex and differentiated into pyramidal and nonpyramidal profiles that expressed different neuronal markers. Glial precursors were shown to proliferate in the slice and in the neotissue, and to differentiate into astrocytes. We show that cells expressing reelin in the marginal zone of embryonic cortical slices persist after a week in culture, which implies that neuronal migration is not necessarily hindered by the presumed stop signals provided by reelin in the marginal zone. Furthermore, our results provide a new model for in vitro studies of migration and differentiation during cortical development.