Book of abstracts - British Neuroscience Association
Book of abstracts - British Neuroscience Association
Book of abstracts - British Neuroscience Association
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25.04<br />
The L1 cell adhesion family and their interaction with the 4.1<br />
superfamily<br />
Lissa Herron(1), Davey F(1), Maria Hill(1), Aviva Tolkvosky(2), Diane<br />
Sherman (3), Peter Brophy (3), Frank Gunn-Moore(1)<br />
(1) School <strong>of</strong> Biology, Bute Medical Building, University <strong>of</strong> St Andrews,<br />
Scotland, UK. KY16 9TS, (2) Dept Biochemistry,, University <strong>of</strong><br />
Cambridge, Building 0,, The Downing Site, Cambridge CB2 1QW, UK,<br />
(3)Division <strong>of</strong> Veterinary Biomedical Sciences, University <strong>of</strong><br />
Edinburgh, Summerhall, Edinburgh EH9 1QH<br />
The L1 immunoglobulin (Ig) subfamily <strong>of</strong> cell adhesion molecules<br />
includes L1, NrCAM, (Neuron glial-related cell adhesion molecule) and<br />
neur<strong>of</strong>ascin. Their fundamental importance in mammalian<br />
development is highlighted by their constituting 1% <strong>of</strong> all membrane<br />
proteins in mature brains; their involvement in growth cone and<br />
synapse formation, and cancer development. Mutations can lead to<br />
human retardation and knockout studies show phenotypic changes.<br />
We have shown that these receptors bind to differing cytoplasmic<br />
proteins and so elicit differing signals. From these studies we found<br />
that both neur<strong>of</strong>ascin and L1 but not NrCAM, can bind to the 4.1<br />
superfamily protein member, Ezrin, but by different binding motifs.<br />
Physiologically the interaction <strong>of</strong> Neur<strong>of</strong>ascin and Ezrin appears to<br />
occur in the microvilli <strong>of</strong> interdigitating Schwann cells over the node <strong>of</strong><br />
Ranvier, whilst L1 and Ezrin interaction is important for neuronal<br />
growth. This interaction between Neur<strong>of</strong>ascin and Ezrin was via the<br />
FERM (4.1 Ezrin-Radixin-Moesin) domain <strong>of</strong> Ezrin and 28 amino acid<br />
sequence at the cytoplasmic C-terminus <strong>of</strong> Neur<strong>of</strong>ascin. As part <strong>of</strong><br />
these studies, we identified a novel FERM containing protein, “Willin”.<br />
Willin has a recognizable N-terminal FERM domain, which is able to<br />
bind both phospholipids and proteins. Recently Willin has been<br />
identified as the human homologue to the Drosophila protein,<br />
Expanded, which associates with Merlin, a tumour suppressor protein<br />
responsible for neur<strong>of</strong>ibromatosis. We have shown that Willin is<br />
expressed in the peripheral nervous system in Schwann cells and we<br />
are currently investigating its association with Neur<strong>of</strong>ascin and Merlin.<br />
25.05<br />
Theta frequency-induced bursting <strong>of</strong> dentate gyrus cells correlates<br />
with long-term synaptic plasticity<br />
Tsanov M, Manahan-Vaughan D<br />
International Graduate School <strong>of</strong> <strong>Neuroscience</strong>, Ruhr University Bochum,<br />
FNO 1/116, Universitaetsstr 150 44780 Bochum, Germany<br />
Neocortico-hippocampal transfer <strong>of</strong> new spatial information occurs during<br />
exploratory behaviour. The entorhinal cortex encodes, in a theta rhythmassociated<br />
manner, particular representations in subsets <strong>of</strong> hippocampal<br />
neurons where memories are temporarily held. However, it remains<br />
unclear, how neuronal cooperativity during theta oscillations is powerful<br />
enough to bring about the nondecremental synaptic change required to<br />
achieve this. We report that long-term potentiation occurs in the dentate<br />
gyrus after phasic activation <strong>of</strong> entorhinal afferents in the theta-frequency<br />
range in freely moving rats. This plasticity is proportional to the bursting<br />
ability <strong>of</strong> granule cells during the stimulation, and may comprise a key step<br />
in spatial information transfer. Long-term potentiation <strong>of</strong> the synaptic<br />
component results only after temporal proximity between the afferent<br />
stimulus and the evoked population burst. Our findings confirm<br />
synchronization-dependent memory models and gap the transition between<br />
functional and pathological patterns <strong>of</strong> network activity in hippocampus.<br />
26.0<br />
Nitric oxide, bioenergetics and cell signalling<br />
Moncada S<br />
Wolfson Institute for Biomedical Research, University College London,<br />
Gower Street, London WC1E 6BT<br />
At physiological concentrations nitric oxide (NO) inhibits mitochondrial<br />
complex IV (cytochrome c oxidase) in competition with oxygen. This<br />
action allows NO to act not only as a physiological regulator <strong>of</strong> cell<br />
respiration but also as a signalling agent in the mitochondria. Using a<br />
technique that we have developed based on visible light spectroscopy<br />
we have recently demonstrated that endogenous NO enhances the<br />
reduction <strong>of</strong> the mitochondrial electron transport chain, thus<br />
contributing to a mechanism whereby cells maintain their VO2 at low<br />
[O2]. This favours the release <strong>of</strong> superoxide anion, which initiates the<br />
transcriptional activation <strong>of</strong> NF-ÜB as an early signalling stress<br />
response.<br />
Many cells respond to a decrease in oxygen availability via<br />
transcriptional activation <strong>of</strong> hypoxia-inducible genes. Activation <strong>of</strong><br />
these genes requires the stabilisation <strong>of</strong> hypoxia-inducible factor-1Ü<br />
(HIF-1Ü) whose accumulation is normally prevented by the action <strong>of</strong><br />
prolyl hydroxylases. We have found that inhibition <strong>of</strong> mitochondrial<br />
respiration by low concentrations <strong>of</strong> NO leads to inhibition <strong>of</strong> HIF-1Ü|<br />
stabilisation. This prevents the cell from registering a state <strong>of</strong> hypoxia<br />
at low oxygen concentrations, which would normally lead to the<br />
upregulation <strong>of</strong> defensive genes associated with, for example,<br />
glycolysis and angiogenesis. Furthermore, upon inhibition <strong>of</strong><br />
mitochondrial respiration in hypoxia, oxygen is redistributed toward<br />
non-respiratory oxygen-dependent targets. The relevance <strong>of</strong> these<br />
mechanisms to the survival/death <strong>of</strong> cells from the nervous system will<br />
be discussed.<br />
27.0<br />
Insights into the molecular basis <strong>of</strong> memory<br />
Collingridge G L<br />
MRC Centre for Synaptic Plasticity, Department <strong>of</strong> Anatomy, School <strong>of</strong><br />
Medical Sciences, University Walk, Bristol, BS8 1TD, UK<br />
Understanding the molecular basis <strong>of</strong> information storage in the brain<br />
requires a concerted multidisciplinary approach involving all areas <strong>of</strong><br />
neuroscience. My group has focussed on one aspect <strong>of</strong> the topic, namely<br />
the identification <strong>of</strong> molecular events that are involved in the modification <strong>of</strong><br />
synaptic strength. Using long-term potentiation (LTP) and long-term<br />
depression (LTD) in the hippocampus as our experimental model we have<br />
identified the roles <strong>of</strong> glutamate receptors (AMPA, NMDA, kainate and<br />
mGluR), some proteins that interact with glutamate receptors (e.g., NSF,<br />
PICK1) and some downstream signalling molecules (protein tyrosine<br />
phosphatase, glycogen synthase kinase (GSK3)) in these plastic<br />
processes. In addition to using electrophysiology we have exploited<br />
imaging techniques to study the behaviour <strong>of</strong> native and recombinant<br />
glutamate receptors and their associated calcium signals during synaptic<br />
plasticity.<br />
I will present an overview <strong>of</strong> our work which has helped establish these<br />
molecules in synaptic plasticity and will discuss some <strong>of</strong> our recent work, in<br />
which we have identified a role for GSK3 in cross-talk between LTP and<br />
LTD.<br />
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