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

L Adermark, DM Lovinger - Journal of Neuroscience, 2007 - Soc Neuroscience
L Adermark, DM Lovinger
Journal of Neuroscience, 2007Soc Neuroscience
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]-1 H-pyrrole-3-carboxylic acid methylester (FPL64176), combined
with modest postsynaptic depolarization and synaptic activation, is sufficient to induce robust …
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-3-carboxylic 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-3-carboxylic 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 D2 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 D2 receptors can be bypassed if this channel is activated.
Soc Neuroscience