Increased excitability and compromised long-term potentiation in the neocortex of NPC1−/− mice

Niemann–Pick type C1 (NPC1) disease is a neurodegenerative lysosomal storage disorder caused by mutations in the NPC1 gene which encodes a transmembrane protein of the acidic compartment. Albeit the NPC1−/− mouse is available serving as an appropriate animal model of the human disease, the precise function of this protein remains obscure. Here, we investigated the synaptic consequences of this disease and explored long-term potentiation (LTP) in slices taken from the hippocampal CA1 region, the dorsomedial striatum as well as the somatosensory neocortex in NPC1−/− mice using extracellular field potential recordings. We did not observe significant changes in synaptic excitability as well as LTP in the hippocampal CA1 region and the dorsomedial striatum of NPC1−/− mice when compared to wildtype littermates. However, neocortical excitability was significantly enhanced while LTP was abolished. These results suggest that at least in the somatosensory neocortex NPC1 protein is instrumental in synaptic function.

► NPC1−/− mouse, modeling Niemann–Pick type C1 disease, was investigated in vitro. ► Changes in network excitability and synaptic plasticity were assessed. ► Three different regions were investigated: hippocampus, striate body, and neocortex. ► No changes were seen in hippocampus and striatum. ► In neocortex, excitability was significantly enhanced while LTP was abolished.