Synaptic plasticity in the dy2J mouse model of laminin α2-deficient congenital muscular dystrophy

Abstract

Laminin α2-deficient congenital muscular dystrophy is a debilitating disease affecting both muscle and neural tissue as a result of mutations in the LAMA2 gene. It presents at or soon after birth with muscle weakness and is further characterised by clinical central nervous system involvement. Laminin α2 is part of the extracellular matrix, linked to the cellular cystoskeleton via dystroglycan which is an integral part of the dystrophin–glycoprotein complex (DGC). We examined both short- and long-term synaptic plasticity in the C57BL6J/ dy 2J mouse, an animal model of laminin α2 deficient congenital muscular dystrophy. Using a cerebellar slice preparation, we show that the pre-synaptically mediated paired-pulse facilitation (PPF) was no different between dy 2J and littermate controls. Approximately half (7/12) the dy 2J Purkinje cells displayed a blunted LTD compared to littermate controls, and one third (4/12) of dy 2J Purkinje cells displayed LTP. This study demonstrates that a defective laminin α2 causes a disruption in long-term synaptic plasticity at the Purkinje cell-parallel fibre synapse.