Paul Barrow - Research Fellow
Neuroscience Unit, Department of Physiology, University of Birmingham,
UK
As you saw from the previous page, my specific interest within the group
is in prion disease. Previous work performed by the group suggests that
the endogenous, normal prion protein (PrPC) is required for normal synaptic
function, being especially important for normal synaptic transmission via
GABAA receptors (Collinge et al., Nature 370, 295-297). When scrapie prion
(PrPSc) isolates are introduced into mice bearing endogenous hamster PrPC,
electrophysiological recordings from hippocampus and neocortex resemble
those from the same brain areas in models of epilepsy where GABAergic transmission
is disrupted (Jefferys et al., Neurobiol.Disease 1, 25-30). The obvious
question is whether the abnormal responses seen in the scrapie infected
animals is due to the loss of normal, functional PrPC as it is converted
to PrPSc, or is the epileptiform activity due to the alteration of other
cellular mechanisms ?
In order to address this question, I am using in vitro extracellular and
sharp electrode intracellular electrophysiological techniques to investigate
network and cellular properties in Sc237 infected hamsters. To address the
specific issue of whether GABAA receptor-mediated currents are disrupted
in this model, I am using voltage clamp to characterise locally and distally
evoked isolated IPSCs in both hippocampus and neocortex.
