Title: Calcium Dependent Inactivation of Calcium Channels in the Medial Striatum Increases at Eye 1 Opening 2 3 4 Running Head: Cdi in Striatal Neurons during Development Introduction

22 Influx of calcium through voltage gated calcium channels (VGCCs) is essential for striatal 23 function and plasticity. VGCCs expressed in striatal neurons have varying kinetics, voltage 24 dependences and densities resulting in heterogeneous subcellular calcium dynamics. One 25 factor that determines the calcium dynamics in striatal medium spiny neurons is inactivation of 26 VGCCs. Aside from voltage dependent inactivation, VGCCs undergo calcium-dependent 27 inactivation (CDI): inactivating in response to an influx of calcium. CDI is a negative feedback 28 control mechanism; however its contribution to striatal neuron function is unknown. 29 Furthermore, though the density of VGCC expression changes with development, it is unclear 30 whether CDI changes with development. Because calcium influx through L-type calcium 31 channels is required for striatal synaptic depression, a change in CDI could contribute to age 32 dependent changes in striatal synaptic plasticity. Here we use whole cell voltage clamp to 33 characterize CDI over developmental stages and across striatal regions. We find that CDI 34 increases at the age of eye opening in the medial striatum, but not the lateral striatum. The 35 developmental increase in CDI mostly involves L-type channels, though calcium influx through 36 non-L-type channels contributes to the CDI in both age groups. Agents that enhance protein 37 kinase A (PKA) phosphorylation of calcium channels reduce the magnitude of CDI after eye 38 opening, suggesting that the developmental increase in CDI may be related to a reduction in 39 the phosphorylation state of the L-type calcium channel. These results are the first to show that 40 modifications in striatal neuron properties correlate with changes to sensory input. 41