@article {Yang15660, author = {Li Yang and Zilai Wang and Baiping Wang and Nicholas J. Justice and Hui Zheng}, title = {Amyloid Precursor Protein Regulates Cav1.2 L-type Calcium Channel Levels and Function to Influence GABAergic Short-Term Plasticity}, volume = {29}, number = {50}, pages = {15660--15668}, year = {2009}, doi = {10.1523/JNEUROSCI.4104-09.2009}, publisher = {Society for Neuroscience}, abstract = {Amyloid precursor protein (APP) has been strongly implicated in the pathogenesis of Alzheimer{\textquoteright}s disease (AD). Although impaired synaptic function is believed to be an early and causative event in AD, how APP physiologically regulates synaptic properties remains poorly understood. Here, we report a critical role for APP in the regulation of L-type calcium channels (LTCC) in GABAergic inhibitory neurons in striatum and hippocampus. APP deletion in mice leads to an increase in the levels of Cav1.2, the pore-forming subunit of LTCCs, and subsequent increases in GABAergic calcium currents (ICa2+) that can be reversed by reintroduction of APP. Upregulated levels of Cav1.2 result in reduced GABAergic paired-pulse inhibition and increased GABAergic post-tetanic potentiation in both striatal and hippocampal neurons, indicating that APP modulates synaptic properties of GABAergic neurons by regulating Cav1.2. Furthermore, APP physically interacts with Cav1.2, suggesting a mechanism in which loss of APP leads to an inappropriate accumulation and aberrant activity of Cav1.2. These results provide a direct link between APP and calcium signaling and might help explain how altered APP regulation leads to changes in synaptic function that occur with AD.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/29/50/15660}, eprint = {https://www.jneurosci.org/content/29/50/15660.full.pdf}, journal = {Journal of Neuroscience} }