Book of abstracts - British Neuroscience Association

17.03
Activity-independent and dependent mechanisms for the
formation of the thalamocortical projection
Yamamoto N, Uesaka N, Hayano Y, Yamada A
Cellular and Molecular Neurobiology, Graduate School of Frontier
Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-
0871
During development, thalamocortical (TC) axons form elaborate
branches in the specific layers of the neocortex. The target- and
activity-dependent mechanisms of TC axon branching were
investigated in organotypic coculture preparations of the thalamus and
cortex. Axon tracing with enhanced yellow fluorescent protein
demonstrated that TC axons formed extensive branches during the
second week in culture. Simultaneously, spontaneous firing activity
emerged in both thalamic and cortical neurons. To study the role of
the spontaneous activity in branch formation, TC axon branching was
examined in the presence of the drugs that block synaptic or firing
activities. The result demonstrated that lamina-specific branch
formation was suppressed considerably by addition of these blockers.
What aspect of TC axon branching is affected by neural activity was
further investigated by time-lapse imaging of individual axons. TC
axon branching was found to be generated dynamically by addition
and elimination, with a preference toward branch accumulation in the
target layer. Blockade of firing or synaptic activity reduced the
remodeling process, in particular, branch addition in the target layer.
Together, these findings suggest that TC axon branching is regulated
by the remodeling process with branch-inducing and inhibiting
molecules and that neural activity can modify the molecular
mechanisms.
17.04
Specificity and plasticity in thalamocortical connectivity: lessons from
Semaphorin-6A mutant mice
Little G, López-Bendito G, Rünker A E, Molnár Z, Mitchell K J
Smurfit Institute of Genetics, Trinity College Dublin, Ireland; (2) Department
of Human Anatomy and Genetics, University of Oxford, UK; 3Instituto de
Neurociencias, San Juan de Alicante, Spain.
The mechanisms controlling the specificity of connectivity between thalamic
nuclei and cortical areas are not well understood. There is good evidence
to support targeting of thalamic axons to specific regions of the cortex but
also to suggest that the “identity” of cortical areas may be defined by their
thalamic innervation. We have observed in Semaphorin-6A mutant mice a
defect in connectivity from thalamus to cortex. This is specific to the visual
axons from the thalamus that would normally project to the visual part of
the cortex. In Sema6A mutants these axons project inappropriately into the
amygdala. In their absence occipital cortex is partially invaded by
somatosensory axons leading to a shift of cortical domains, which persists
in adults. The Sema6A mutant mice are the first animals that show this type
of phenotype that survive to adulthood. As such they are a unique model in
which to explore the targeting of thalamocortical axons and the
specification of cortical areas.
18.01
Are there stem cells in the olfactory system
Barnett S, Tome M, Toft A, Riddell J
1Division of Clinical Neurosciences. Beatson Labs, Glasgow
University, Glasgow G61 1BD. ^IBLS, University of Glasgow G12 8QQ
The peripheral olfactory system is thought to contain stem cells. To
assess the stem cell properties of these cells, we compared their
ability to form neurospheres and to differentiate in vitro with CNS
neural stem cells. Brain and olfactory mucosa (OM) of embryonic rats
were processed using a standard methodology for CNS neurosphere
culture. Primary spheres were formed by both tissues but OM-spheres
rarely formed secondary spheres. OM-spheres exhibited two main
morphologies, one which resembled CNS neurospheres, (type-I) the
second which was smaller and more tightly formed (type-II). As
expected brain neurospheres were strongly positive for the stem cell
marker nestin and differentiated into typical neural cells. The type-I
OM-spheres, although expressing nestin also expressed markers for
peripheral glia and connective tissue. The type-II spheres were mainly
cytokeratin positive, a marker of sustentacular and horizontal basal
cells. To assess the potential of olfactory cells in CNS repair we used
a partial transection model of SC injury. We compared the
regenerative capacity of a mixed population of OM cells with OMspheres.
Both types of transplant survived and filled the injury site.
Mixed mucosa grafts produced an extensive graft environment that
supported axonal ingrowth and myelination. OM-sphere grafts
produced less extensive graft areas in general. These were
characterised by the presence of large spheres into which there was
little axon ingrowth or consisted of a more diffuse cellular environment
into which some axonal ingrowth occurred. Thus neurospheres from
the olfactory mucosa have no particular advantage over candidate
cells for CNS repair.
18.02
Embryonic solutions for adult problems
Chandran S
Cambridge Centre for Brain Repair, UK
Repair of the damaged brain has long been regarded as the holy grail of
regenerative medicine. The emergence of stem cells as an experimental
and therapeutic resource represents a major opportunity for brain repair.
Although repair need not necessarily recapitulate development, insights
rooted in an understanding of developmental principles are central to the
design of novel neural repair strategies. Human embryonic stem cells
(hESCs) are an attractive source of defined tissue for cell-based therapies
and drug screening in regenerative neurology. In order for their therapeutic
potential to be realised, there is a need for controlled and large-scale
differentiation of hESCs into defined neural precursors without the use of
animal products or genetic manipulation. Derivation of hESC-NSCs under
defined conditions will be discussed.
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