bluuebunny/crossref_metadata_2025_split huggingface dataset:
An identified central pattern‐generating neuron co‐ordinates sensory‐motor components of respiratory behavior in Lymnaea
Authors: Haque Zara , Lee Thomas K. M. , Inoue Takuya , Luk Collin , Hasan Shabih U. , Lukowiak Ken , Syed Naweed I. 
Published: January 2006

AbstractDefining the attributes of individual central pattern‐generating (CPG) neurons underlying various rhythmic behaviors are fundamental to our understanding of how the brain controls motor programs, such as respiration and locomotion. To this end, we have explored a simple invertebrate preparation in which the neuronal basis of respiratory rhythmogenesis can be investigated from the whole animal to a single cell level. An identified dopaminergic neuron, termed right pedal dorsal 1 (RPeD1), is a component of the CPG network which controls hypoxia‐driven, aerial respiration in the fresh water snail Lymnaea stagnalis. Using intact, semi‐intact and isolated brain preparations, we have discovered that in addition to its role as a respiratory CPG neuron, RPeD1 co‐ordinates sensory‐motor input from the pneumostome (the respiratory orifice) at the water/air interface to initiate respiratory rhythm generation. An additional, novel role of RPeD1 was also found. Specifically, direct intracellular stimulation of RPeD1 induced pneumostome openings, in the absence of motor neuronal activity. To determine further the role of RPeD1 in the respiratory behavior of intact animals, either its axon was severed or the soma selectively killed. Many components of the respiratory behavior in the intact animals were found to be perturbed following RPeD1 axotomy or ‘somatomy’ (soma removed). Taken together, the data presented provide a direct demonstration that RPeD1 is a multifunctional CPG neuron, which also serves many additional roles in the control of breathing behavior, ranging from co‐ordination of mechanosensory input to the motor control of the respiratory orifice.
Hitting Ras where it counts: Ras antagonism in the basolateral amygdala inhibits long‐term fear memory
Authors: Merino Stephen M. , Maren Stephen 
Published: January 2006

AbstractSeveral studies have implicated the Ras/mitogen‐activated protein kinase (MAPK) pathway in Pavlovian fear conditioning. RasGRF1 knockout mice show significant deficits in acquisition of long‐term fear memories and long‐term potentaition (LTP) in the basolateral amygdala (BLA). MAPK kinase inhibition also impairs fear conditioning and amygdaloid LTP. However, there is no direct evidence to date for the involvement of Ras itself in fear conditioning. To address this issue, we examined the effects of intra‐amygdala infusions of the selective Ras antagonist farnesylthiosalicylic acid (FTS) on the acquisition and expression of conditional freezing in rats. Micro‐infusions of FTS into the BLA prior to contextual fear conditioning significantly impaired acquisition of long‐term contextual fear memory in a dose‐dependent manner. Post‐training FTS infusions had no effect on acquisition of long‐term fear memory. The effects of FTS on fear conditioning were specific for the BLA. Finally, intra‐amygdala infusions of FTS inhibited MAPK activation in BLA. Collectively, these results provide further evidence for the involvement of amygdaloid Ras in the acquisition of long‐term conditional fear memory.
Caspase‐like activity is essential for long‐term synaptic plasticity in the terrestrial snail Helix
Authors: Bravarenko N. I. , Onufriev M. V. , Stepanichev M. Yu , Ierusalimsky V. N. , Balaban P. M. , Gulyaeva N. V. 
Published: January 2006

AbstractAlthough caspase activity in the nervous system of mollusks has not been described before, we suggested that these cysteine proteases might be involved in the phenomena of neuroplasticity in mollusks. We directly measured caspase‐3 (DEVDase) activity in the Helix lucorum central nervous system (CNS) using a fluorometrical approach and showed that the caspase‐3‐like immunoreactivity is present in the central neurons of Helix. Western blots revealed the presence of caspase‐3‐immunoreactive proteins with a molecular mass of 29 kDa. Staurosporin application, routinely used to induce apoptosis in mammalian neurons through the activating cleavage of caspase‐3, did not result in the appearance of a smaller subunit corresponding to the active caspase in the snail. However, it did increase the enzyme activity in the snail CNS. This suggests differences in the regulation of caspase‐3 activity in mammals and snails. In the snail CNS, the caspase homolog seems to possess an active center without activating cleavage typical for mammals. In electrophysiological experiments with identified snail neurons, selective blockade of the caspase‐3 with the irreversible and cell‐permeable inhibitor of caspase‐3 N‐benzyloxycarbonyl‐Asp(OMe)‐Glu(OMe)‐Val‐Asp‐(OMe)‐fluoro‐methylketone prevented development of the long‐term stage of synaptic input sensitization, suggesting that caspase is necessary for normal synaptic plasticity in snails. The results of our study give the first direct evidence that the caspase‐3‐like activity is essential for long‐term plasticity in the invertebrate neurons. This activity is presumably involved in removing inhibitory constraints on the storage of long‐term memory.
Blockade of mGluR5 glutamate receptors in the subthalamic nucleus ameliorates motor asymmetry in an animal model of Parkinson's disease
Authors: Phillips Janice M. , Lam Hoa A. , Ackerson Larry C. , Maidment Nigel T. 
Published: January 2006

AbstractIt has been suggested that Group I metabotropic glutamate receptor antagonists could have potential therapeutic value in the treatment of Parkinson's disease. There is evidence that when given systemically, 2‐methyl‐6‐(phenylethynyl)‐pyridine (MPEP), a metabotropic glutamate receptor type 5 (mGluR5) antagonist, produces anti‐parkinsonian effects in animal models, but the site of action has not been directly established. In the present study, we examined whether the subthalamic nucleus (STN) and its output structures may mediate such an effect using a unilateral rat model of Parkinson's disease. A battery of simple behavioral tests, reliably sensitive to dopamine depletion, was applied consecutively: (i) prior to surgery; (ii) 3 weeks following a unilateral 6‐hydroxydopamine lesion of the substantia nigra pars compacta; (iii) at 1 h, 24 h and 4 days following a microinjection of MPEP, via an indwelling cannula, into the STN, entopeduncular nucleus (EP) or substantia nigra zona reticulata. Unilaterally dopamine‐depleted animals typically had severe motor and sensorimotor asymmetries 3 weeks following surgery. Microinjection of 25 nmol MPEP into the STN of these animals significantly attenuated these asymmetries relative to vehicle. Further microinjections of lower doses (5 and 10 nmol) revealed a dose–response effect. Microinjection of MPEP into either the EP or substantia nigra zona reticulata was without effect. These data suggest that MPEP may act at the level of the STN to reduce glutamatergic overactivity and thereby induce anti‐parkinsonian effects.
Temporal memory deficits in Alzheimer's mouse models: rescue by genetic deletion of BACE1
Authors: Ohno Masuo , Chang Lei , Tseng Wilbur , Oakley Holly , Citron Martin , Klein William L. , Vassar Robert , Disterhoft John F. 
Published: January 2006

AbstractTransgenic mouse models of Alzheimer's disease (AD) exhibit amyloid‐β (Aβ) accumulation and related cognitive impairments. Although deficits in hippocampus‐dependent place learning have been well characterized in Alzheimer's transgenic mice, little is known about temporal memory function in these AD models. Here, we applied trace fear conditioning to two different Alzheimer's mouse models and investigated the relationship between pathogenic Aβ and temporal memory deficits. This behavioral test requires hippocampus‐dependent temporal memory processing as the conditioned and unconditioned stimuli are separated by a trace interval of 30 s. We found that both amyloid precursor protein (APP) transgenic (Tg2576) and APP/presenilin (PS)1 transgenic (Tg6799) mice were impaired in memorizing this association across the time gap. Both transgenic groups performed as well as wild‐type control mice in delay fear conditioning when the trace interval was removed, indicating that the trace conditioning deficits are hippocampus‐specific. Importantly, Tg6799 mice engineered to lack the major Alzheimer's β‐secretase (β‐site APP‐cleaving enzyme 1: BACE1) showed behavioral rescue from temporal memory deficits. Elevated levels of soluble Aβ oligomers found in Tg6799+ mouse brains returned to wild‐type control levels without changes in APP/PS1 transgene expression in BACE1–/–·Tg6799+ bigenic mouse brains, suggesting Aβ oligomers as potential mediators of memory loss. Thus, trace fear conditioning is a useful assay to test the mechanisms and therapeutic interventions for Aβ‐dependent deficits in temporal associative memory. Our gene‐based approach suggests that lowering soluble Aβ oligomers by inhibiting BACE1 may be beneficial for alleviating cognitive disorders in AD.
Long‐lasting modulation of the induction of LTD and LTP in rat hippocampal CA1 by behavioural stress and environmental enrichment
Authors: Artola Alain , Von Frijtag Josefien C. , Fermont Patrick C. J. , Gispen Willem Hendrik , Schrama Loes H. , Kamal Amer , Spruijt Berry M. 
Published: January 2006

AbstractBehavioural experience (e.g. chronic stress, environmental enrichment) can have long‐lasting effects on cognitive functions. Because activity‐dependent persistent changes in synaptic strength are believed to mediate memory processes in brain areas such as hippocampus, we tested whether behaviour has also long‐lasting effects on synaptic plasticity by examining the induction of long‐term potentiation (LTP) and long‐term depression (LTD) in slices of hippocampal CA1 obtained from rats either 7–9 months after social defeat (behavioural stress) or 3–5 weeks after 5‐week exposure to environmental enrichment. Compared with age‐matched controls, defeated rats showed markedly reduced LTP. LTP was even completely impaired but LTD was enhanced in defeated and, subsequently, individually housed (during the 7–9‐month period after defeat) rats. However, increasing stimulus intensity during 100‐Hz stimulation resulted in significant LTP. This suggests that the threshold for LTP induction is still raised and that for LTD lowered several months after a short stressful experience. Both LTD and LTP were enhanced in environmentally enriched rats, 3–5 weeks after enrichment, as compared with age‐matched controls. Because enrichment reduced paired‐pulse facilitation, an increase in presynaptic release, facilitating both LTD and LTP induction, might contribute to enhanced synaptic changes. Consistently, enrichment reduced the number of 100‐Hz stimuli required for inducing LTP. But enrichment may also actually enhance the range of synaptic modification. Repeated LTP and LTD induction produced larger synaptic changes in enriched than in control rats. These data reveal that exposure to very different behavioural experiences can produce long‐lasting effects on the susceptibility to synaptic plasticity, involving pre‐ and postsynaptic processes.
Developmental changes of CaMKII localization, activity and function during postembryonic CNS remodelling in Manduca sexta
Authors: Burkert P. , Duch C. 
Published: January 2006

AbstractInsect metamorphosis is a compelling example of postembryonic remodelling of neuronal structure and synaptic connectivity as larval and adult behaviours place distinct demands on the CNS. Holometabolous insects such as the moth Manduca sexta have long served as suitable models for the study of steroid effects on CNS remodelling, but activity and calcium‐dependent mechanisms have been found to act in concert with hormonal signals. This study examines developmental changes in the localization and the activational state of CaMKII during postembryonic Manduca CNS remodelling. Western blotting, CaMKII purification and autophosphorylation with γ32P‐ATP indicate that the lepidopteran CNS may contain only one CaMKII isoform. In situ immunohistochemistry reveals developmental changes in the expression patterns of CaMKII in different types of thoracic neurons and in different neuronal compartments. Early pupal life is characterized by an increase in postsynaptic CaMKII localization, which coincides with a developmental increase in CaMKII activation. Both events correlate temporally with motoneuron dendritic filopodia collapse and rapid synaptogenesis, indicating a possible functional role for CaMKII for the postembryonic development of invertebrate motor circuitry. Substrate phosphorylation assays demonstrate that CaMKII activity in the ventral nerve cord reflects changes in calcium influx through voltage‐activated channels as occurring in vivo during normal development.
Neurogenesis in the adult spinal cord in an experimental model of multiple sclerosis
Authors: Danilov Alexandre I. , Covacu Ruxandra , Moe Morten C. , Langmoen Iver A. , Johansson Clas B. , Olsson Tomas , Brundin Lou 
Published: January 2006

AbstractMultiple sclerosis is an inflammatory disease of the central nervous system characterized by inflammation, demyelination, axonal degeneration and accumulation of neurological disability. Previously, we demonstrated that stem cells constitute a possible endogenous source for remyelination. We now addressed the question of whether neurogenesis can occur in neuroinflammatory lesions. We demonstrated that, in experimental autoimmune encephalomyelitis, induced in rats 1,1′‐dioctadecyl‐6,6′‐di(4sulphopentyl)‐3,3,3′,3′tetramethylindocarbocyanin(DiI)‐labelled ependymal cells not only proliferated but descendants migrated to the area of neuroinflammation and differentiated into cells expressing the neuronal markers β‐III‐tubulin and NeuN. Furthermore, these cells were immunoreactive for bromodeoxyuridine and PCNA, markers for cells undergoing cell proliferation. Using the whole‐cell patch‐clamp technique on freshly isolated 1, DiI‐labelled cells from spinal cord lesions we demonstrated the ability of these cells to fire overshooting action potentials similar to those of immature neurones. We thus provide the first evidence for the initiation of neurogenesis in neuroinflammatory lesions in the adult spinal cord.
Serotonergic modulation of neuronal responses to behavioural inhibition and reinforcing stimuli: an fMRI study in healthy volunteers
Authors: Völlm Birgit , Richardson Paul , McKie Shane , Elliott Rebecca , Deakin J. F. W. , Anderson Ian M. 
Published: January 2006

AbstractSerotonin (5‐HT) has been implicated in the aetiology of a number of psychiatric conditions, including depression, anxiety and antisocial personality disorder. The development of these disorders may arise from alterations in underlying motivational and cognitive processes such as emotional recognition, reinforcement processing and central inhibitory control. This study aimed to localize where in the brain 5‐HT modulates neuropsychological processes relevant to putative 5‐HT disorders, using functional magnetic resonance imaging. We examined the effect of the antidepressant mirtazapine on brain activations associated with behavioural inhibition and reinforcement processing in healthy subjects. Forty‐five men were randomly allocated to receiving mirtazapine or placebo in a double‐blind fashion. A Go/No‐Go, Reward/No‐Reward and Loss/No‐loss task were performed during functional magnetic resonance imaging using a 1.5 Tesla Philips Gyroscan scanner. Blood oxygenation level dependent (BOLD) responses were analysed using SPM2. Task activations were largely consistent with previous findings. Mirtazapine modulated brain activations in the Go/No‐Go and Reward/No‐Reward task. During behavioural inhibition, enhanced activations were observed in the right orbitofrontal cortex (BA47). Increased activations in bilateral parietal cortex were found during the Reward task while no significant interaction was observed in the Loss task. Our results support the suggestion of an important role of serotonin in modulating basic processes involved in psychiatric disorders. Combining drug challenge with fMRI (pharmacoMRI; pMRI) is a promising tool for investigating these processes in healthy as well as patient groups.
Intraischemic mild hypothermia prevents neuronal cell death and tissue loss after neonatal cerebral hypoxia–ischemia
Authors: Zhu Changlian , Wang Xiaoyang , Xu Falin , Qiu Lin , Cheng Xiuyong , Simbruner George , Blomgren Klas 
Published: January 2006

AbstractThe effectiveness of hypothermia in preventing ischemic brain damage depends on when it is started. The purpose of this study was to investigate the effects of temperature reduction during a hypoxic–ischemic (HI) insult on brain injury and signalling pathways of neuronal cell death and survival. Seven‐day‐old mice were subjected to left common carotid artery ligation and hypoxia (10% oxygen) at different temperatures (37, 36 or 34 °C) for 50 min. Brain injury at 7 days post‐HI was significantly reduced from 67.4% at 37 °C to 31.6% at 36 °C and 10% at 34 °C, with no observable injury in the cortex of the 34 °C group. Cytochrome c release, caspase‐3 activation and apoptosis‐inducing factor translocation from mitochondria to nuclei were all significantly inhibited after intraischemic temperature reduction. Concurrently, the cell survival signalling pathway involving Akt was significantly sustained (the phosphorylated form of Akt was maintained) when the hypoxia temperature was decreased. These results indicate that intraischemic hypothermia diminished apoptosis through inhibition of both caspase‐dependent and caspase‐independent neuronal cell death pathways and promoted cell survival by inhibition of phosphorylated Akt dephosphorylation in the neonatal brain, thereby preventing neuronal cell death.
Intracellular acidification in neurons induced by ammonium depends on KCC2 function
Authors: Titz Stefan , Hormuzdi Sheriar , Lewen Andrea , Monyer Hannah , Misgeld Ulrich 
Published: January 2006

AbstractThe Cl–‐extruding neuron‐specific K+–Cl– cotransporter KCC2, which establishes hyperpolarizing inhibition, can transport NH4+ instead of K+. It is, however, not clear whether KCC2 provides the only pathway for neuronal NH4+ uptake. We therefore investigated NH4+ uptake in cultured rat brain neurons. In neurons cultured for > 4 weeks, the response to NH4Cl applications (5 mm) consisted of an alkaline shift which reversed to an acid shift within seconds. Rebound acid shifts which followed brief applications of NH4Cl were blocked by furosemide (100 µm). They were rather insensitive to bumetanide (1 and 100 µm), in contrast to those induced in cultured glial cells. Rebound acid shifts persisted in the presence of 1 mm Ba2+ and in Na+‐free solution but were inhibited by extracellular K+. In neurons with depolarizing GABA responses, indicating the absence of functional KCC2, applications of NH4Cl barely induced an acidosis. However, large rebound acid shifts occurred in neurons that had changed their GABA response from Ca2+ increases to Ca2+ decreases. Rebound acid shifts continued to increase even after the change in the GABA response had occurred and could be induced earlier in neurons transfected with KCC2 cDNA. We conclude that KCC2 provides the main pathway for fast neuronal NH4+ uptake. Therefore, NH4Cl‐induced rebound acid shifts can be used to indicate the development of KCC2 function. Further, the well known up‐regulation of KCC2 function during development has the inevitable consequence of opening a major pathway for NH4+ influx, which can be relevant under pathophysiological conditions.
Long‐term depression of neuron to glial signalling in rat cerebellar cortex
Authors: Bellamy Tomas C. , Ogden David 
Published: January 2006

AbstractBergmann glial cells enclose synapses throughout the molecular layer of the cerebellum and express extrasynaptic AMPA receptors and glutamate transporters. Accordingly, stimulation of parallel fibres leads to the generation of inward currents in the glia due to AMPA receptor activation and electrogenic uptake of glutamate. Elimination of AMPA receptor Ca2+ permeability leads to the withdrawal of glial processes and synaptic dysfunction, suggesting that AMPA receptor‐mediated Ca2+ signalling is essential for glial support of the neuronal network. Here we show that glial extrasynaptic currents (ESCs) exhibit activity‐dependent plasticity, specifically, long‐term depression during repetitive stimulation of parallel fibres at low frequencies (0.033–1 Hz) − conditions in which Purkinje neuron excitatory postsynaptic currents (EPSCs) remain stable. Both the rate of onset and the magnitude of ESC depression increased with stimulation frequency. Depression was reversible following brief periods of stimulation, but became increasingly persistent as the duration of repetitive stimulation increased. All glial currents − AMPA receptors, glutamate transporter and a recently discovered slow 1,2,3,4‐tetrahydro‐6‐nitro‐2,3‐dioxo‐benzo[f]quinoxaline‐7‐sulphonamide (NBQX)‐sensitive current − were depressed. Increasing presynaptic release probability by doubling external Ca2+ concentration did not affect the time course of depression, suggesting that neither decreased release probability nor fatigue of release sites contribute to depression. Inhibition of glutamate uptake caused a dramatic enhancement of the rate of depression, implicating glutamate in the underlying mechanism. The strength of neuron to glial signalling in the cerebellum is therefore dynamically regulated, independently of adjacent synapses, by the frequency of parallel fibre activity.
Immunological and virological responses to highly active antiretroviral therapy in a non‐clinical trial setting in a developing Caribbean country
Authors: Kilaru KR , Kumar A , Sippy N , Carter AO , Roach TC 
Published: January 2006

ObjectiveFew data exist on the efficacy of antiretroviral therapy in individuals infected with HIV in the Caribbean. We evaluated the virological and immunological responses of HIV‐infected adults starting highly active antiretroviral therapy (HAART).DesignThis was a prospective observational cohort study.MethodsA total of 158 antiretroviral‐naive patients who initiated HAART between January 2002 and March 2003, and completed at least 6 months of treatment and follow up, were included in the analysis. The response to therapy was assessed by changes in CD4 cell counts and viral loads from baseline. The mean increase in CD4 cell count, the rate of virological success (a viral load of <50 HIV‐1 RNA copies/mL) and the rate of immunological success (an increase in CD4 cell count of≥50 cells/μL over the baseline value) after commencing HAART were measured.ResultsIn total, 82% of patients (123 of 150) achieved viral loads of <50 copies/mL after 6 months of therapy. Viral success rate after 6 months of HAART was similar irrespective of gender, pre‐HAART CD4 cell count and pre‐HAART viral load. However, patients older than 40 years were significantly more likely to achieve virorological success than those younger than 40 years. At 6 months after starting HAART, 79.5% of patients were estimated to have achieved immunological success and 17.9% had an increase in CD4 cell count of ≥200 cells/μL over the baseline value. The median increase in CD4 cell count for the 156 patients who had CD4 cell counts at baseline and at 6 months of therapy was 122 cells/μL.ConclusionIn this cohort of antiretroviral‐naive HIV‐infected adults, there was a high rate of virological and immunological success after 6 months of HAART, irrespective of the pre‐HAART viral load and CD4 cell count.