Upstate Channel Switch

Abstract

Medium spiny neurons (MSNs) of the striatum are key regulators of voluntary movement, and loss or deregulation of these neurons causes movement disorders, such as Huntington's or Parkinson's disease. These GABAergic neurons are activated by glutamatergic input to their dendritic spines. MSNs exist in a resting (—80 mV membrane potential) and an "upstate" (—50 mV membrane potential). Carter and Sabatini used 2-photon laser-scanning microscopy (2PLSM) and 2-photon laser uncaging of glutamate to investigate the calcium signals generated in resting or upstate MSNs in rat striatal slices. Calcium signals were larger and longer lasting in upstate cells, with the largest increase detected in the dendritic spine head. Using pharmacological inhibitors of different classes of voltage-gated calcium channels (VGCCs), the authors determined that stimulation of resting cells activates T-type and R-type VGCCs, and stimulation of upstate cells activates L-type and R-type VGCCs. Resting cells also respond to localized uncaging of glutamate with a fast Ca 2+ transient mediated by AMPA receptors and a slower, prolonged Ca 2+ transient mediated by N -methyl D aspartate (NMDA) receptors. Comparing responses in resting and upstate cells indicated a strong AMPA receptor contribution in resting cells and a dominant NMDA receptor contribution in upstate cells. These results indicate that differences in calcium signaling observed in resting and upstate MSNs arise from changes in the contributions of different classes of VGCCs and glutamate receptors. A. G. Carter, B. L. Sabatini, State-dependent calcium signaling in dendritic spines of striatal medium spiny neurons. Neuron 44 , 483-493 (2004). [Online Journal]