Combined activation of L-type Ca2+ channels and synaptic transmission is sufficient to induce striatal long-term depression

Changes in synaptic strength at striatal synapses, such as long- term depression ( LTD), may be involved in striatal- based learning and memory. Several molecular mechanisms have been implicated in striatal LTD, but it is not clear which mechanisms are crucial for LTD induction. We found that the activation of L- type calcium channels by 2,5- dimethyl- 4-[ 2-( phenylmethyl) benzoyl]- 1H- pyrrole- 3carboxylic acid methylester ( FPL64176), combined with modest postsynaptic depolarization and synaptic activation, is sufficient to induce robust LTD ( FPL - LTD). The L- channel activator 1,4- dihydro- 2,6- dimethyl- 5- nitro- 4-[ 2( trifluoromethyl) phenyl] pyridine- 3carboxylic acid methyl ester ( Bay K 8644) has a similar action. FPL - LTD occludes LTD induced by high- frequency stimulation ( HFS LTD) and requires elevated postsynaptic calcium and retrograde endocannabinoid signaling, properties similar to those of HFS - LTD. In contrast, FPL - LTD does not require the activation of metabotropic glutamate receptors ( mGluRs), phospholipase C, or dopamine D-2 receptors. FPL - LTD induction also requires afferent stimulation. These findings suggest a scenario in which L- type calcium channel activation is a crucial switch for LTD induction, and mGluRs and D-2 receptors can be bypassed if this channel is activated.