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-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.
Adermark
Louise
L
Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA.
Lovinger
David M
DM
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D051379:Mice; D009433:Neural Inhibition / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology*
D020746:Calcium Channels, L-Type; D002118:Calcium