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

J.L. Anderson, S.I. Head and J.W. Morley, School of Medical Sciences, UNSW, NSW 2052, Australia.

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.