Book of abstracts - British Neuroscience Association

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22.04 Inflammation and CNS remyelination Franklin R J M , Cambridge Centre for Brain Repair, University of Cambridge, Cambridge CB3 OES, UK, Remyelination, the process by which new myelin sheaths are restored to demyelinated axons, represents one of the most compelling examples of adult multipotent stem/precursor cells contributing to regeneration of the injured CNS. This process can occur with remarkable efficiency in both clinical disease, such as multiple sclerosis, and in experimental models, revealing an impressive ability of the adult CNS to repair itself. However, the inconsistency of remyelination in multiple sclerosis, and the loss of axonal integrity that results from its failure, makes enhancement of remyelination an important therapeutic objective. Identifying potential targets will depend on a detailed understanding of the cellular and molecular mechanisms of remyelination. This talk will review 1) the nature of the cell or cells that respond to demyelination and generate new oligodendrocytes, 2) the concept of inflammation-induced adult progenitor activation, 3) how an environment favourable to remyelination is generated by inflammation, and 4) will introduce the concept of a matrix of signalling events critical for the successful completion of remyelination. 23.01 Mechanisms of adenosine release in the basal forebrain and control of sleep Dale N Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL Adenosine, an important homoeostatic regulator of sleep, accumulates in the brain during wakefulness and dissipates during sleep. In the basal forebrain and preoptic areas these increased levels of adenosine lead to slow wave sleep. The mechanisms by which adenosine accumulates during wakefulness, and disappears during sleep remain opaque. I have examined the mechanisms of adenosine release in the basal forebrain in vitro using patch clamp recordings and novel real-time biosensor measurements. Although depolarization is a sufficient stimulus for adenosine release, only selective depolarizing stimuli (activation of NMDA, AMPA or mGlu receptors) are able to evoke adenosine release. Other powerful depolarizing stimuli of basal forebrain neurons such as orexin, neurotensin and histamine do not evoke adenosine release. Adenosine release evoked by high K+, AMPA, NMDA and mGlu receptors does not require extracellular Ca2+, suggesting that neuronal exocytosis cannot underlie its production. This glutamate receptor mediated adenosine release exhibits diurnal variation and can be significantly enhanced by prior sleep deprivation. Some aspects of adenosine accumulation related to sleep homoeostasis can therefore be studied in vitro. I suggest that activitydependent release of adenosine (mediated via glutamate receptors) coupled with diurnal variation in the capacity to release adenosine could explain the sleep-wake cycle of adenosine accumulation and removal. Identification of the adenosine-releasing cells will greatly assist the understanding of adenosine-dependent mechanisms of sleep homeostasis. 23.02 The role of ATP in the brain mechanisms controlling breathing Gourine A V, Dale N, Spyer K M Department of Physiology, University College London, Gower Street, London WC1E 6BT and *Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom There has been increasing interest in the role of purines in the nervous system. In addition to its known role as an intracellular energy source, ATP also functions as an extracellular signalling molecule in the brain and many peripheral tissues. Immunohistochemical studies demonstrate the presence of ATP receptors throughout the brainstem structures involved in respiratory control. Results obtained in our laboratory indicate that ATP-mediated purinergic signalling indeed plays an important role in the brain mechanisms controlling breathing. Using transgenic animal models we have demonstrated that ATP acting via ionotropic P2X2 receptors is essential for the development of normal ventilatory response to hypoxia. It was also found that ATP mediates central respiratory CO2 chemosensory transduction in the medulla oblongata. Recently we obtained evidence suggesting that ATP is also involved in central afferent processing – ATP is released with glutamate from the central terminals of slowly adapting lung stretch receptors to activate second-order relay neurones. Thus, it emerges that ATP acts as a common mediator of peripheral and central chemosensory transduction and also contributes to neurotransmission at a first central synapse in the Breuer-Hering reflex pathway. These data reveal the importance of purinergic signalling in the brainstem mechanisms underlying respiratory control (Supported by the BBSRC and the Wellcome Trust). 23.03 Astrocytic purinergic signaling coordinates synaptic networks Haydon P G Department of Neuroscience, University of Pennsylvania School of Medicine, Many recent studies have demonstrated that astrocytes release chemical transmitters in a process termed gliotransmission. Though gliotransmission can modulate synaptic transmission and neuronal excitability, it is less clear how this process regulates neuronal networks. We have generated inducible, astrocyte-specific transgenic mice which express a dominant negative SNARE domain that suppresses vesicular exocytosis and consequently reduces the release of gliotransmitters from astrocytes. Using brain slices from this animal we demonstrate that excitatory synaptic transmission at the Schaffer collateral CA1 synapse is augmented when gliotransmission is suppressed, a result which arises from a reduction in extracellular adenosine. These studies demonstrate that astrocytes regulate adenosine which causes a presynaptic inhibition of synaptic transmission. Neighboring synaptic pathways exhibit adenosine-mediated heterosynaptic depression. Using dnSNARE transgenic animals our results demonstrate that activation of astrocytes leads to ATP release, which following hydrolysis to adenosine, results in the depression of neighboring synapses. Since each astrocyte contacts tens of thousands of synapses, our results indicate that astrocytes are able to coordinate groups of synapses in the hippocampus. Because of the potential for adenosine in the control of sleep and seizures, current studies are examining neural networks in vivo to test the hypothesis that astrocytes are critically involved in these two processes. Supported by funds from the NINDS and NIMH Page 36/101 - 10/05/2013 - 11:11:03
23.04 Adenosine, astrogliosis and epilepsy: a rational approach for novel cell and gene therapies Boison D R.S. Dow Neurobiology Laboratories, , Legacy Research, , Portland OR, , USA Adenosine is an inhibitory modulator of brain activity with neuroprotective and anticonvulsant properties. In adult brain, extracellular levels of adenosine are mainly regulated by intracellular metabolism via the astrocyte-based enzyme adenosine kinase (ADK), which removes adenosine via phosphorylation to AMP. Recent evidence suggests that ADK expression undergoes rapid and coordinated changes during brain development and following brain injury, such as after status epilepticus or stroke. Thus, after acute brain injury, transient downregulation of ADK initially protects the brain from seizures and cell death. However, astrogliosis as a chronic response to brain injury leads to overexpression of ADK, which can cause seizures and promote cell death in epilepsy. To address the role of ADK in epileptogenesis, we created a panel of transgenic mice with either elevated levels of brain ADK (160%, Adk-tg), or reduced levels of forebrain ADK (60%, fb-Adk-def). Subjecting these animals to intraamygdaloid kainic acid injections revealed that even subtle changes in ADK expression render the brain more vulnerable (Adk-tg) or more resistant (fb-Adk-def) to subsequent epileptogenesis. In line with these findings intrahippocampal implants of ADK-deficient – and thus adenosine releasing – ES cell derived neural progenitor cells retard the development of kindling epileptogenesis in rats. ES cell derived brain implants showed integration into the CA1 region of the hippocampus and neuronal differentiation. We conclude that tight regulation of ambient levels of adenosine by ADK controls the vulnerability of the brain but also offers a rationale for therapeutic intervention. 24.01 Behavioural feedback and circadian rhythms Piggins H D Faculty of Life Sciences, University of Manchester, Manchester UK M13 9PT Daily rhythms in mammalian physiology and behaviour are a product of the activities of the master circadian clock in the suprachiasmatic nuclei (SCN) and the entrainment of this clock to photic cues (the light-dark cycle) and arousal-promoting, non-photic cues such as social interactions, food availability, etc. The SCN is composed of thousands of autonomous cellular clocks and the past 5 years has seen considerable progress in understanding the mechanisms via which these clock cells become synchronized to one another. Vasoactive intestinal polypeptide (VIP) acting via the VPAC2 receptor has emerged as a key SCN intercellular signalling pathway involved in such processes. Transgenic mice deficient in VIP (VIP- /-) or the VPAC2 receptor (Vipr2-/-) manifest profoundly disrupted circadian competence, reduced SCN neuronal excitability, and do not respond properly to photic cues. It is unknown if behavioural rhythms in these mice can be altered by non-photic cues. Using a schedule of daily locomotor activity whereby mice voluntarily exercised in a running wheel for 6h/day, we found that this non-photic stimulus reorganizes and sculpts locomotor rhythms in VIP-/- and Vipr2-/- mice, such that they can sustain robust near 24h rhythms in behaviour. These findings indicate that behavioural feedback is more effective than light in resynchronizing rhythms in mice with impaired neuropeptide signalling, raising the possibility that scheduled exercise can be used as rescue circadian competence in organisms with impaired circadian clocks. Supported by the BBSRC. 24.02 Melatonin in the avian pineal gland and retina – photic, circadian, and neurochemical regulations Zawilska J B Centre for Medical Biology, Polish Academy of Sciences and Department of Pharmacodynamics, Medical University of Lodz, Poland The avian pineal gland and retina synthesize melatonin in a lightdependent circadian rhythm with high levels at night. The rate of melatonin formation is regulated primarily by serotonin N- acetyltransferase (AANAT). Circadian oscillations in AANAT activity were found in pineal glands and retinas of chickens and turkeys kept under constant darkness, or continuous light (pineals only). Exposure to white light and near-ultraviolet radiation (UV-A) acutely suppressed nocturnal AANAT activity and melatonin. This light action is mediated by D4-dopamine receptors in the retina and alpha2-adrenergic receptors in the pineal, and involves decrease in cAMP, ultimately leading to the proteosomal destruction of AANAT protein. Light also resets the circadian pacemaker generating melatonin rhythm. Pulses of light applied during the first and second half of the night produced phase delay and phase advance, respectively, of the circadian rhythm of AANAT activity in the pineal gland and retina. In galliforms, pineal activity, in addition to being directly photosensitive, is regulated by retinally perceived light. White light and UV-A, acting on the eyes only, suppressed nocturnal melatonin synthesis in the pineal gland. Both light signals were also capable of resetting the phase of the circadian rhythm of pineal AANAT activity. It is suggested that regulation of melatonin synthesis in the chicken pineal by retinally perceived white light and UV-A might involve input from different photoreceptors. The cascade of events triggered by white light and UV-A includes stimulation of retinal D1-dopamine and NMDA-glutamate receptors, respectively. 24.03 Circadian plasticity of neurons and glial cells Pyza E, Gorska-Andrzejak J, Weber P, Radowska A Department of Cytology and Histology, Institute of Zoology, Jagiellonian University,, Ingardena 6, 30-060 Krakow, Poland, In the visual system of flies, the first order interneurons, the lamina monopolar cells L1 and L2 and epithelial glial cells show circadian rhythms in morphological changes. These rhythms have been detected in three species; Musca domestica, Calliphora vicina and Drosophila melanogaster. In all species the cross-sectional area of L1 and L2 axons changes during the day and night (LD) and also under constant darkness (DD) and continuous light (LL) conditions, indicating on their endogenous generation by a circadian clock. In the housefly both neurons swell during the day and shrink during night while the epithelial glial cells show the opposite pattern of morphological changes, swelling during the night. Using Drosophila transgenic line in which L2 cells are labelled with green fluorescent protein (GFP) we showed that beside L2 axons, dendrites and nuclei, but not somata, change their sizes. These changes are under control of clock genes since in per01 mutants, L2 morphology do not change in LD and DD. Daily changes of glial cell morphology were detected in another Drosophila transgenic line expressing GFP under control of glia specific gene repo. Like in M. domestica, glial cells in Drosophila are larger when L2 are shrank. The changes in morphology of L2 and glial cells seem to correlate with daily changes of synaptic contacts between the photoreceptors and monopolar cells in the lamina and with expression of certain genes. Page 37/101 - 10/05/2013 - 11:11:03
Page 1 and 2: 1.0 Paths to recovery: Modulating P
Page 3 and 4: 3.07 Congenital hypothyroidism alte
Page 5 and 6: 4.01 The effect of hippocampal slic
Page 7 and 8: 4.09 ß-adrenergic modulation of in
Page 9 and 10: 5.03 Constitutively active Ras and
Page 11 and 12: 6.07 Proteomic identification of bi
Page 13 and 14: 8.01 Dietary flavonoids stimulate P
Page 15 and 16: 9.04 Inducing neural differentiatio
Page 17 and 18: 10.02 The effect of PAT (thymulin r
Page 19 and 20: 10.10 Immuno-regulatory T cell func
Page 21 and 22: 11.04 Expression profile of mesench
Page 23 and 24: 12.01 Use of capillary chip based p
Page 25 and 26: 13.06 Contribution of synaptic cond
Page 27 and 28: 15.01 L-serine enhances the inhibit
Page 29 and 30: 16.03 Quantitative analysis of memb
Page 31 and 32: 18.03 Finding cells for replacement
Page 33 and 34: 20.01 Cannabinoid neuropharmacology
Page 35: 21.05 Spatial arrangement of cortic
Page 39 and 40: 25.04 The L1 cell adhesion family a
Page 41 and 42: 28.05 The effects of the FAAH inhib
Page 43 and 44: 28.13 Genetic determinants of ethan
Page 45 and 46: 29.02 A HAP1-kinesin protein traffi
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Page 49 and 50: 29.18 Supporting study skills: work
Page 51 and 52: 33.02 Noradrenaline reuptake inhibi
Page 53 and 54: 35.01 Synchrony and sensory coding
Page 55 and 56: 37.01 Nitric oxide inhibition incre
Page 57 and 58: 37.09 Behavioural and electrophysio
Page 59 and 60: 39.06 The role of glutamate recepto
Page 61 and 62: 40.03 Live imaging of Per1 driven G
Page 63 and 64: 41.01 A polymorphism at the 3’ un
Page 65 and 66: 43.02 Neuroleptic treatment worsens
Page 67 and 68: 43.10 Biochemical estimates of SNAR
Page 69 and 70: 45.01 Mutant SOD1-PUMA knockout dou
Page 71 and 72: 47.03 VAP proteins Skehel P Center
Page 73 and 74: 49.04 Regulation of synaptic functi
Page 75 and 76: 51.04 The use of MRI for tracking d
Page 77 and 78: 53.04 The role of the pedunculopont
Page 79 and 80: 56.06 Dissecting exploratory behavi
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Page 83 and 84: 57.09 Cognitive rigidity and altere
Page 85 and 86: 57.17 An analysis of DJ-1 (PARK7) a
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58.05 Differential effects of Inter
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59.05 Blockade of paw incision-indu
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60.07 2-Dimensional gel electrophor
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63.02 Subpyrogenic systemic inflamm
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64.08 Modulation of ketamine-induce
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65.08 The anti-inflammatory role of
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68.01 A comparison of carbachol and
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69.06 Comparison of data analysis t
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