Compartmentalized Ca(2+) channel regulation at divergent mossy-fiber release sites underlies target cell-dependent plasticity.
Hippocampal mossy fibers (MFs) innervate CA3 targets via anatomically distinct presynaptic elements: MF boutons (MFBs) innervate pyramidal cells (PYRs), whereas filopodial extensions (Fils) of MFBs innervate st. lucidum interneurons (SLINs). Surprisingly, the same high-frequency stimulation (HFS) protocol induces presynaptically expressed LTP and LTD at PYR and SLIN inputs, respectively. This differential distribution of plasticity indicates that neighboring, functionally divergent presynaptic elements along the same axon serve as autonomous computational elements capable of modifying release independently. Indeed we report that HFS persistently depresses voltage-gated calcium channel (VGCC) function in Fil terminals, leaving MFB VGCCs unchanged despite similar contributions of N- and P/Q-type VGCCs to transmission at each terminal. Selective Fil VGCC depression results from HFS-induced mGluR7 activation leading to persistent P/Q-type VGCC inhibition. Thus, mGluR7 localization to MF-SLIN terminals and not MFBs allows for MF-SLIN LTD expression via depressed presynaptic VGCC function, whereas MF-PYR plasticity proceeds independently of VGCC alterations.
Pelkey
Kenneth A
KA
Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Building 35, Bethesda, Maryland 20892, USA. pelkeyk2@mail.nih.gov
Topolnik
Lisa
L
Lacaille
Jean-Claude
JC
McBain
Chris J
CJ
D000818:Animals; D002118:Calcium; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D003521:Cyclopropanes / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D011422:Propionates / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects
C114785:2-amino-4-phosphono-propinate; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003521:Cyclopropanes; D011422:Propionates; D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D002118:Calcium; D005998:Glycine