Altered Cerebellar Short-Term Plasticity but No Change in Postsynaptic AMPA-Type Glutamate Receptors in a Mouse Model of Juvenile Batten Disease

Juvenile Batten disease is the most common progressive neurodegenerative disorder of childhood. It is associated with mutations in the CLN3 gene, causing loss of function of CLN3 protein and degeneration of cerebellar and retinal neurons. It has been proposed that changes in granule cell AMPA-type glutamate receptors (AMPARs) contribute to the cerebellar dysfunction. In this study, we compared AMPAR properties and synaptic transmission in cerebellar granule cells from wild-type and Cln3 knock-out mice. In Cln3(Δex1–6) cells, the amplitude of AMPA-evoked whole-cell currents was unchanged. Similarly, we found no change in the amplitude, kinetics, or rectification of synaptic currents evoked by individual quanta, or in their underlying single-channel conductance. We found no change in cerebellar expression of GluA2 or GluA4 protein. By contrast, we observed a reduced number of quantal events following mossy-fiber stimulation in Sr(2+), altered short-term plasticity in conditions of reduced extracellular Ca(2+), and reduced mossy fiber vesicle number. Thus, while our results suggest early presynaptic changes in the Cln3 (Δ)(ex1–6) mouse model of juvenile Batten disease, they reveal no evidence for altered postsynaptic AMPARs.