Absence seizures occur in many types of
epilepsy but they are not well understood.
In absence seizures, epileptic activity
arises in the thalamus (which relays messages
from our senses) and the cortex (the outermost
layer of the brain). This study will investigate
the mechanisms of how these seizures happen,
focusing particularly on the principal inhibitory
messenger chemical in the brain, GABA, and
its activity in the thalamus and cortex.
GABA carries messages from neurone to neurone
via receptors at their synapses (the linking
points at the end of their long arms). However,
GABA is also involved in a recently-discovered
type of communication between neurones called
"tonic inhibition". This is a
constant background drift of the inhibitory
neurotransmitter to receptors located outside
the synapses. This slows the cells' rate
of communicating.
Dr David Cope, of School of Biosciences,
Cardiff University has shown that this type
of inhibition is doubled in brain tissue
from the thalamus affected by absence seizures.
This means there has been a change in the
number of receptors that can interact with
GABA in this way. It's not yet clear how
widespread these changes are, or exactly
how they lead to seizures. Dr Cope has been
awarded £184,017 in the 2008
Epilepsy Research UK Fellowship to investigate
whether similar changes also occur in cortex
cells affected by absence seizures, and
also to look at the mechanisms that cause
these changes.
His 3-year study is called Extrasynaptic
GABAA receptor-mediated
gain-of-function in absence seizures.
Dr Cope hopes his work will improve our
understanding of how absence seizures happen,
leading potentially to new ways of tackling
them with drugs, and also to the identification
of genes that can cause this type of seizures.
