Programme Contents

Reduced long-term depression is recovered in aging mdx cerebellar Purkinje cells

Duchenne muscular dystrophy (DMD) is characterized primarily by a loss of skeletal muscle and marked CNS and cognitive defects (Anderson et al,, 2002). It is known that DMD is due to the mutation of a gene which produces the protein dystrophin, of which there are seven identified isoforms, expressed in a range of tissues including brain. In the cerebellum an isoform of dystrophin is found exclusively in Purkinje neurons and is selectively localised in post-synaptic regions of GABAergic synapses. We have previously demonstrated (Anderson et al,, 2004) a deficit in long-term depression (LTD) in cerebellar Purkinje cells in the mdx mouse (an animal model of DMD) compared to controls at 3 months of age. In the present study we investigated LTD and short-term plasticity at the parallel fibre to Purkinje cell synapse in cerebellar brain slices from ageing (6-12 months) control and mdx mice. Mice were anaesthetised with halothane, decapitated, cerebellum removed, bisected, placed in ice-cold aCSF and sagittal slices (250μM) cut. Individual Purkinje cells were visualised using a 40× immersion lens and IR-DIC optics. Intracellular electrodes (∼120MΩ) filled with potassium acetate were used and a stimulating electrode was placed in the molecular layer of the slice (<250μM from the cell under study). We found that the deficit in LTD which we reported (Anderson et al,, 2004) in mdx mice at 3 months of age was no longer evident in aging mdx mice, and that these cells showed a long lasting and robust LTD. In addition, there were no differences in short-term plasticity between the ageing control and mdx mice.

Anderson, J.L., Head, S.I., Rae, C. & Morley, J.W. (2002) Brain 125, 4-13.

Anderson, J.L., Head. S.I. & Morley, J.W. (2004) Brain Research 1019, 289-92.