bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion of the adenosine A1 receptor gene does not alter neuronal damage following ischaemia in vivo or in vitro
Authors: Olsson Tomas , Cronberg Tobias , Rytter Anna , Asztély Fredrik , Fredholm Bertil B. , Smith Maj‐Lis , Wieloch Tadeusz 
Published: September 2004

AbstractExtracellular adenosine is dramatically increased during cerebral ischaemia and is considered to be neuroprotective due to its inhibitory effect on synaptic transmission mediated by the adenosine A1 receptor (A1R). We investigated the importance of the A1R in a mouse model of global ischaemia and in a murine hippocampal slice culture model of in vitro ischaemia, using mice with the A1R gene deleted. In brains from mice lacking the A1R, damage induced by global ischaemia was similar to that in wild‐type animals. In contrast, treatment with a selective A1R antagonist [8‐cyclo‐pentyl theophylline (8‐CPT)], administered before the ischaemic insult in naive wild‐type mice, exacerbated the neuronal damage following global ischaemia. Although the inhibitory action of adenosine on excitatory neurotransmission in hippocampal slices was lost in A1R knockout mice, there was no difference in damage between slices from wild‐type and knockout mice after in vitro ischaemia. The results suggest that some effects of the A1R are compensated for in knockout animals.
Independent coding of connected environments by place cells
Authors: Paz‐Villagrán V. , Save E. , Poucet B. 
Published: September 2004

AbstractPlace cells are hippocampal neurons that have a strong location‐specific firing activity in the rat's current environment. Collectively, place cells also provide a signature of the rat's environment as their ensemble activity is markedly different when recorded in distinct apparatuses. This phenomenon, referred to as ‘remapping’, suggests that each environment activates a different hippocampal map. In this study, we sought to determine the independence of such maps. In Experiment 1, we used a cylinder apparatus that was divided into two equal halves by a central barrier with an aperture allowing the rat to freely commute between the two sides. A local change in one side failed to induce field remapping in the changed side, thus precluding any significant conclusion to be drawn. We therefore designed Experiment 2 in which place cells were first recorded while rats explored three distinct high‐walled boxes. Most cells had distinctive firing fields in each box. A runway was then added to connect two initially unrelated boxes. This manipulation altered the firing of some cells but the fields in each box were still clearly distinguishable. The final manipulation consisted of changing one box and allowing the rat to commute freely between the changed and unchanged boxes. While the firing fields remapped in the changed box, they were most usually unaltered in the unchanged box. These results suggest that the hippocampus holds a set of independent maps for each box, and that each specific map is activated mainly according to the rat's current sensory environment.
Optical detection of neural function in the chick visual pathway in the early stages of embryogenesis
Authors: Miyakawa Naohisa , Sato Katsushige , Momose‐Sato Yoko 
Published: September 2004

AbstractWe investigated the developmental pattern of functional synaptogenesis in the chick visual pathway using a multiple‐site optical recording method. Responses to optic nerve stimulation were recorded from the diencephalon and mesencephalon of the chick embryo. The first excitatory postsynaptic responses to optic nerve stimulation appeared in the contralateral diencephalon at Hamburger–Hamilton stage 27, which corresponds to an incubation day 5.5 (E5.5). At more developed stages, the optical signals evoked by optic nerve stimulation spread to several different regions, including the tectum and extra‐tectal visual nuclei. We constructed maps of neural activity in the diencephalon and mesencephalon at different stages to investigate the spatio‐temporal patterns of functional development in the chick visual system. The maps revealed that distinct postsynaptic response areas in the extra‐tectal regions showed different onsets of activity, suggesting that the corresponding visual nuclei exhibit different time courses of functional synaptogenesis. We also identified the onset and location of the first functional synaptic connection in the optic tectum, which had been a point of controversy in earlier studies. In the tectal region, the action potential and the excitatory postsynaptic potential first appeared at E8, although these signals were recognized in the tecto/tegmental region at E7. The response area expanded with retinotectal fibre elongation, and reached the area centralis at E9. These results show that the onset of synaptic function in the tectum occurs 2–3 days earlier than was previously reported.
Effects of muscarinic acetylcholine receptor activation on membrane currents and intracellular messengers in medium spiny neurones of the rat striatum
Authors: Lin John Y. , Chung Kenny K. H. , De Castro Denis , Funk Gregory D. , Lipski Janusz 
Published: September 2004

AbstractAcetylcholine, acting through muscarinic receptors, modulates the excitability of striatal medium spiny neurones. However, the underlying membrane conductances and intracellular signalling pathways have not been fully determined. Our aim was to characterize excitatory effects mediated by M1 muscarinic acetylcholine receptors in these neurones using whole‐cell patch‐clamp recordings in brain slices of postnatal rats. Under voltage‐clamp, muscarine evoked an inward current associated with an increase in cell membrane resistance. The current, which reversed at −85 mV, was sensitive to the M1 receptor antagonist pirenzepine. Blocking the potassium conductance attenuated the response and the residual current was further reduced by ruthenium red (50 µm) and reversed at +15 mV. Simultaneous recordings from cholinergic interneurones and medium spiny neurones in conjunction with spike‐triggered averaging revealed small unitary excitatory postsynaptic currents in four of 39 cell pairs tested. The muscarine‐induced inward current was attenuated by a phospholipase C (PLC) inhibitor, U73122, but not by a protein kinase C inhibitor, chelerythrine, or by the intracellular calcium chelator 1,2‐bis(2‐aminophenoxy) ethane‐N,N,N′,N′‐tetra‐acetic acid, suggesting that the current was associated with PLC in a protein kinase C‐ and Ca2+‐independent manner. The phosphatidylinositol 4‐kinase inhibitor wortmannin (10 µm) reduced the recovery of the inward current, indicating that the recovery process was dependent on the removal of diacylglycerol and/or inositol 1,4,5 triphosphate or resynthesis of phospholipid phosphatidylinositol 4,5‐bisphophate. Ratiometric measurement of intracellular calcium after cell loading with fura‐2 demonstrated a muscarine‐induced increase in calcium signal that originated mainly from intracellular stores. Thus, the cholinergic excitatory effect in striatal medium spiny neurones, which is important in motor disorders associated with altered cholinergic transmission in the striatum such as Parkinson's disease, is mediated through M1 receptors and the PLC‐dependent pathway.
Integration and differentiation of neural stem cells after transplantation into the dysmyelinated central nervous system of adult mice
Authors: Ader Marius , Schachner Melitta , Bartsch Udo 
Published: September 2004

AbstractMutant mice deficient in the myelin‐associated glycoprotein (MAG) and the nonreceptor‐type tyrosine kinase Fyn are characterized by a severely hypomyelinated central nervous system (CNS) and morphologically abnormal myelin sheaths. Despite this pronounced phenotype, MAG/Fyn‐deficient mice have a normal longevity. In the present study, we took advantage of the normal life expectancy of this myelin mutant and grafted neural stem cells (NSCs) into the CNS of MAG/Fyn‐deficient mice to study in short‐ and long‐term experiments the fate of NSCs in adult dysmyelinated brains. Neural stem cells were isolated from spinal cords of transgenic mouse embryos ubiquitously expressing enhanced green fluorescent protein. Cells were expanded in vitro in the presence of mitogens for up to 5 weeks before they were grafted into the lateral ventricles or injected into white matter tracts. Analysis of mutant brains 3–15 weeks after intracerebroventricular transplantation of NSCs revealed only limited integration of donor cells into the host brains. However, injection of NSCs directly into white matter tracts resulted in widespread distribution of donor cells within the host tissue. Donor cells survived for at least 15 weeks in adult host brains. The majority of grafted cells populated white matter tracts and differentiated into oligodendrocytes that myelinated host axons. Results suggest that intraparenchymal transplantation of NSCs might be a strategy to reconstruct myelin in dysmyelinated adult brains.
BDNF increases rat brain mitochondrial respiratory coupling at complex I, but not complex II
Authors: Markham A. , Cameron I. , Franklin P. , Spedding M. 
Published: September 2004

AbstractBrain‐derived neurotrophic factor (BDNF) governs both the selective survival of neurons during development and the experience‐based regulation of synaptic strength throughout life. BDNF produced a concentration‐dependent increase in the respiratory control index (RCI, a measure of the efficiency of respiratory coupling, ATP synthesis and organelle integrity) of rat brain mitochondria. This effect was mediated via a MAP kinase pathway and highly specific for oxidation of glutamate plus malate (complex I) by brain mitochondria. The oxidation by brain mitochondria of the complex II substrate succinate was unaffected by BDNF. The failure of BDNF to modify respiratory activity associated with mitochondrial preparations isolated from rat liver indicates that the actions of the neurotrophin are tissue specific. BDNF also increased the RCI values associated with Ca2+‐induced respiration to a similar extent. This is the first demonstration that BDNF, in addition to modifying neuronal plasticity, can modify brain metabolism and the efficiency of oxygen utilization. The finding that neurotrophins can alter mitochondrial oxidative efficiency has important implications for neurodegenerative and psychiatric diseases.
Directed interactions between visual areas and their role in processing image structure and expectancy
Authors: Salazar Rodrigo F. , König Peter , Kayser Christoph 
Published: September 2004

AbstractDuring sensory processing, cortical areas continuously exchange information in different directions along the hierarchy. The functional role of such interactions, however, has been the subject of various proposals. Here, we investigate the role of bottom‐up and top‐down interactions in processing stimulus structure and their relation to expected events. Applying multivariate autoregressive methods to local field potentials recorded in alert cats, we quantify directed interactions between primary (A17/18) and higher (A21) visual areas. A trial‐by‐trial analysis yields the following findings. To assess the role of interareal interactions in processing stimulus structure, we recorded in naïve animals during stimulation with natural movies and pink noise stimuli. The overall interactions decrease compared with baseline for both stimuli. To investigate whether forthcoming events modulate interactions, we recorded in trained animals viewing two stimuli, one of which had been associated with a reward. Several results support such modulations. First, the interactions increase compared with baseline and this increase is not observed in a context where food was not delivered. Second, these stimuli have a differential effect on top‐down and bottom‐up components. This difference is emphasized during the stimulus presentation and is maximal shortly before the possible reward. Furthermore, a spectral decomposition of the interactions shows that this asymmetry is most dominant in the gamma frequency range. Concluding, these results support the notion that interareal interactions are more related to an expectancy state rather than to processing of stimulus structure.
The frontal predominance in human EEG delta activity after sleep loss decreases with age
Authors: Münch Mirjam , Knoblauch Vera , Blatter Katharina , Schröder Carmen , Schnitzler Corina , Kräuchi Kurt , Wirz‐Justice Anna , Cajochen Christian 
Published: September 2004

AbstractSleep loss has marked and selective effects on brain wave activity during subsequent recovery sleep. The electroencephalogram (EEG) responds to sleep deprivation with a relative increase in power density in the delta and theta range during non‐rapid eye movement sleep. We investigated age‐related changes of the EEG response to sleep deprivation along the antero‐posterior axis (Fz, Cz, Pz, Oz) under constant routine conditions. Both healthy young (20–31 years) and older (57–74 years) participants manifested a significant relative increase in EEG power density in the delta and theta range after 40 h of sleep deprivation, indicating a sustained capacity of the sleep homeostat to respond to sleep loss in ageing. However, the increase in relative EEG delta activity (1.25–3.75 Hz) following sleep deprivation was significantly more pronounced in frontal than parietal brain regions in the young, whereas such a frontal predominance was diminished in the older volunteers. This age‐related decrease of frontal delta predominance was most distinct at the beginning of the recovery sleep episode. Furthermore, the dissipation of homeostatic sleep pressure during the recovery night, as indexed by EEG delta activity, exhibited a significantly shallower decline in the older group. Activation of sleep regulatory processes in frontal brain areas by an extension of wakefulness from 16 to 40 h appears to be age‐dependent. These findings provide quantitative evidence for the hypothesis that frontal brain regions are particularly vulnerable to the effects of elevated sleep pressure (‘prefrontal tiredness’) and ageing (‘frontal ageing’).
GABAergic phenotypic differentiation of a subpopulation of subventricular derived migrating progenitors
Authors: De Marchis S. , Temoney S. , Erdelyi F. , Bovetti S. , Bovolin P. , Szabo G. , Puche A. C. 
Published: September 2004

AbstractOlfactory bulb interneurons are continuously generated throughout development and in adulthood. These neurons are born in the subventricular zone (SVZ) and migrate along the rostral migratory stream into the olfactory bulb where they differentiate into local interneurons. To investigate the differentiation of GABAergic interneurons of the olfactory bulb we used a transgenic mouse which expresses green fluorescent protein (GFP) under the control of the glutamic acid decarboxylase 65 kDa (GAD65) promoter. During development and in adulthood GFP was expressed by cells in the SVZ and along the entire length of its rostral extension including the distal portion within the olfactory bulb. The occurrence of GAD65 mRNA in these zones was confirmed by PCR analysis on microdissected regions along the pathway. Polysialic acid neural cell adhesion molecule, a marker of migrating neuroblasts in adults, was coexpressed by the majority of the GFP‐positive SVZ‐derived progenitor cells. Cell tracer injections into the SVZ indicated that ≈ 26% of migrating progenitor cells expressed GFP. These data show the early differentiation of migrating SVZ‐derived progenitors into a GAD65–GFP‐positive phenotype. These cells could represent a restricted lineage giving rise to GAD65‐positive GABAergic olfactory bulb interneurons.
GABAergic neurons participate in the brain's response to birdsong auditory stimulation
Authors: Pinaud Raphael , Velho Tarciso A. F. , Jeong Jin K. , Tremere Liisa A. , Leão Ricardo M. , Von Gersdorff Henrique , Mello Claudio V. 
Published: September 2004

AbstractBirdsong is a learned vocal behaviour that requires intact hearing for its development in juveniles and for its maintenance during adulthood. However, the functional organization of the brain circuits involved in the perceptual processing of song has remained obscure. Here we provide evidence that GABAergic mechanisms are an important component of these circuits and participate in the auditory processing of birdsong. We first cloned a zebra finch homologue of the gene encoding the 65‐kDa isoform of glutamic acid decarboxylase (zGAD‐65), a specific GABAergic marker, and conducted an expression analysis by in situ hybridization to identify GABAergic cells and to map their distribution throughout auditory telencephalic areas. The results showed that field L2, the caudomedial nidopallium (NCM) and the caudomedial mesopallium (CMM) contain a high number of GABAergic cells. Using patch‐clamp brain slice recordings, we found abundant GABAergic mIPSCs in NCM. Pharmacological antagonism of mIPSCs induced large EPSC bursts, suggesting that tonic inhibition helps to stabilize NCM against runaway excitation via activation of GABA‐A receptors. Next, using double fluorescence in situ hybridization and double immunocytochemical labelling, we demonstrated that large numbers of GABAergic cells in NCM and CMM show inducible expression of the transcriptional regulator ZENK in response to song auditory stimulation. These data provide direct evidence that GABAergic neurons in auditory brain regions are activated by song stimulation. Altogether, our results suggest that GABAergic mechanisms participate in auditory processing and perception, and might contribute to the memorization of birdsong.
Environmental enrichment in mice decreases anxiety, attenuates stress responses and enhances natural killer cell activity
Authors: Benaroya‐Milshtein N. , Hollander N. , Apter A. , Kukulansky T. , Raz N. , Wilf A. , Yaniv I. , Pick C.G. 
Published: September 2004

AbstractThe importance of environment in the regulation of brain, behaviour and physiology has long been recognized in biological, social and medical sciences. Animals maintained under enriched conditions have clearly been shown to have better learning abilities than those maintained under standard conditions. However, the effects of environmental enrichment (EE) on immunity and emotionality have been less documented and remain questionable. Therefore, we investigated the effect of EE on natural killer (NK) cell activity, psychological stress responses and behavioural parameters. Male C3H mice were housed either in enriched or standard conditions for 6 weeks. Behaviour was then examined by the grip‐strength test, staircase and elevated plus maze, and corticosterone levels and NK cell activity were measured. Furthermore, animals exposed to the stress paradigm, achieved by electric shock with reminders, were tested for freezing time in each reminder. Corticosterone levels were also measured. The EE mice showed decreased anxiety‐like behaviour and higher activity compared to standard mice, as revealed by a greater percentage of time spent in the open arms of the elevated plus maze, and a higher rate of climbing the staircase. A shorter freezing time in the stress paradigm and no corticosterone level reactivity were measured in EE mice. In addition, NK cell activity in spleens of EE mice was higher than that demonstrated in those of standard mice. Thus, EE has a beneficial effect on anxiety‐like behaviour, stress response and NK cell activity. The effect on NK cell activity is promising, due to the role of NK cells in host resistance.
Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions
Authors: Verge Gail M. , Milligan Erin D. , Maier Steve F. , Watkins Linda R. , Naeve Gregory S. , Foster Alan C. 
Published: September 2004

AbstractFractalkine is a unique chemokine reported to be constitutively expressed by neurons. Its only receptor, CX3CR1, is expressed by microglia. Little is known about the expression of fractalkine and CX3CR1 in spinal cord. Given that peripheral nerve inflammation and/or injury gives rise to neuropathic pain, and neuropathic pain may be partially mediated by spinal cord glial activation and consequent glial proinflammatory cytokine release, there must be a signal released by affected neurons that triggers the activation of glia. We sought to determine whether there is anatomical evidence implicating spinal fractalkine as such a neuron‐to‐glia signal. We mapped the regional and cellular localization of fractalkine and CX3CR1 in the rat spinal cord and dorsal root ganglion, under basal conditions and following induction of neuropathic pain, employing both an inflammatory (sciatic inflammatory neuropathy; SIN) as well as a traumatic (chronic constriction injury; CCI) model. Fractalkine immunoreactivity and mRNA were observed in neurons, but not glia, in the rat spinal cord and dorsal root ganglia, and levels did not change following either CCI or SIN. By contrast, CX3CR1 was expressed by microglia in the basal state, and the microglial cellular concentration was up‐regulated in a regionally specific manner in response to neuropathy. CX3CR1‐expressing cells were identified as microglia by their cellular morphology and positive OX‐42 and CD4 immunostaining. The cellular distribution of fractalkine and CX3CR1 in the spinal circuit associated with nociceptive transmission supports a potential role in the mechanisms that contribute to the exaggerated pain state in these models of neuropathy.
Functional repair after dorsal root rhizotomy using nerve conduits and neurotrophic molecules
Authors: Tang Xiao‐Qing , Cai Jie , Nelson Kevin D. , Peng Xue‐Jun , Smith George M. 
Published: September 2004

AbstractFunctional recovery after large excision of dorsal roots is absent because of both the limited regeneration capacity of the transected root, and the inability of regenerating sensory fibers to traverse the dorsal root entry zone. In this study, bioresorbable guidance conduits were used to repair 6‐mm dorsal root lesion gaps in rats, while neurotrophin‐encoding adenoviruses were used to elicit regeneration into the spinal cord. Polyester conduits with or without microfilament bundles were implanted between the transected ends of lumbar dorsal roots. Four weeks later, adenoviruses encoding NGF or GFP were injected into the spinal cord along the entry zone of the damaged dorsal roots. Eight weeks after injury, nerve regeneration was observed through both types of implants, but those containing microfilaments supported more robust regeneration of calcitonin gene‐related peptide (CGRP)‐positive nociceptive axons. NGF overexpression induced extensive regeneration of CGRP(+) fibers into the spinal cord from implants showing nerve repair. Animals that received conduits containing microfilaments combined with spinal NGF virus injections showed the greatest recovery in nociceptive function, approaching a normal level by 7–8 weeks. This recovery was reversed by recutting the dorsal root through the centre of the conduit, demonstrating that regeneration through the implant, and not sprouting of intact spinal fibers, restored sensory function. This study demonstrates that a combination of PNS guidance conduits and CNS neurotrophin therapy can promote regeneration and restoration of sensory function after severe dorsal root injury.