High affinity group III mGluRs regulate mossy fiber input to CA3 interneurons.
Stratum lacunosum-moleculare interneurons (L-Mi) in hippocampal area CA3 target the apical dendrite of pyramidal cells providing feedforward inhibition. Here we report that selective activation of group III metabotropic glutamate receptors (mGluRs) 4/8 with L(+)-2-amino-4-phosphnobytyric acid (L-AP4; 10 μM) decreased the probability of glutamate release from the mossy fiber (MF) terminals synapsing onto L-Mi. Consistent with this interpretation, application of L-AP4 in the presence of 3 mM strontium decreased the frequency of asynchronous MF EPSCs in L-Mi. Furthermore, the dose response curve showed that L-AP4 at 400 μM produced no further decrease in MF EPSC amplitude compared with 20 μM L-AP4, indicating the lack of mGluRs 7 at these MF terminals. We also found that one mechanism of mGluRs 4/8-mediated inhibition of release is linked to N-type voltage gated calcium channels at MF terminals. Application of the group III mGluR antagonist MSOP (100 μM) demonstrated that mGluRs 4/8 are neither tonically active nor activated by low and moderate frequencies of activity. However, trains of stimuli to the MF at 20 and 40 Hz delivered during the application of MSOP revealed a relief of inhibition of transmitter release and an increase in the overall probability of action potential firing in the postsynaptic L-Mi. Interestingly, the time to first action potential was significantly shorter in the presence of MSOP, indicating that mGluR 4/8 activation delays L-Mi firing in response to MF activity. Taken together, our data demonstrate that the timing and probability of action potentials in L-Mi evoked by MF synaptic input is regulated by the activation of presynaptic high affinity group III mGluRs.
Cosgrove
Kathleen E
KE
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Meriney
Stephen D
SD
Barrionuevo
Germán
G
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D056654:CA3 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D003521:Cyclopropanes / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010768:Phosphoserine / Q000494:pharmacology; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology*
D000613:Aminobutyrates; D003521:Cyclopropanes; D018094:Receptors, Metabotropic Glutamate; D017661:Receptors, Presynaptic; C111435:metabotropic glutamate receptor 8; C120877:methylserine phosphate; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D010768:Phosphoserine; C012729:2-amino-4-phosphonobutyric acid; D005998:Glycine; C108823:metabotropic glutamate receptor 4
J Pharmacol Exp Ther. 2001 Oct;299(1):12-20
11561058
J Neurophysiol. 1996 Dec;76(6):3798-806
8985877
J Neurosci. 1988 Apr;8(4):1400-10
3357023
J Comp Neurol. 2009 Aug 20;515(6):677-95
19496174
Neuropharmacology. 1995 Aug;34(8):965-71
8532177
Eur J Neurosci. 2004 May;19(10):2847-58
15147318
J Comp Neurol. 1999 Apr 28;407(1):33-46
10213186
Mol Pharmacol. 1994 Mar;45(3):367-72
8145723
J Physiol. 2005 Jun 15;565(Pt 3):885-96
15845577
Science. 1996 Oct 25;274(5287):594-7
8849448
Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):12004-9
9751780
J Physiol. 2004 Jan 1;554(Pt 1):175-93
14678500
Neuropharmacology. 2005;49 Suppl 1:45-56
15998525
Science. 1998 Feb 27;279(5355):1368-70
9478900
J Physiol. 1996 Jun 1;493 ( Pt 2):447-55
8782108
J Neurosci. 2008 Dec 24;28(52):14042-55
19109487
Nat Neurosci. 2002 Aug;5(8):790-5
12118256
J Neurosci. 1997 Oct 1;17(19):7503-22
9295396
Mol Pharmacol. 1997 Jan;51(1):119-25
9016353
Annu Rev Pharmacol Toxicol. 1997;37:205-37
9131252
Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):18004-9
19815518
J Comp Neurol. 1995 Oct 2;360(4):555-70
8801249
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13304-9
8917586
Nature. 1997 Feb 13;385(6617):630-4
9024660
Neuron. 2006 Nov 9;52(3):497-510
17088215
Results Probl Cell Differ. 2008;44:163-75
17579817
Neuropharmacology. 1995 Nov;34(11):1549-57
8606802
J Neurochem. 2000 Sep;75(3):889-907
10936169
J Neurosci. 1996 Mar 15;16(6):2044-56
8604049
J Biol Chem. 2001 Dec 21;276(51):47877-85
11604405
J Neurosci. 2005 Nov 9;25(45):10520-36
16280590
J Neurosci. 1993 Apr;13(4):1372-8
8463825
J Neurophysiol. 2003 Apr;89(4):1910-9
12686572
J Neurosci. 2000 Nov 15;20(22):8279-89
11069934
J Neurosci. 2007 Dec 5;27(49):13420-9
18057200
Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14708-13
11734656
J Physiol. 2000 May 15;525 Pt 1:41-51
10811723
Br J Pharmacol. 2003 Feb;138(4):614-25
12598415
Nature. 2002 Jan 17;415(6869):327-30
11797010
Curr Neuropharmacol. 2005 Oct;3(4):299-307
18369399
Nat Neurosci. 1998 Nov;1(7):572-8
10196564
J Neurophysiol. 1994 Jun;71(6):2217-35
7931512
Neuroscience. 2002;110(3):403-20
11906782
Cell Tissue Res. 2006 Nov;326(2):483-504
16847639
Hippocampus. 1993 Apr;3(2):165-82
8353604
J Neurosci. 1997 Nov 1;17(21):8137-46
9334389
J Neurophysiol. 2006 Jul;96(1):86-96
16611839
J Neurosci. 2010 Feb 24;30(8):2844-55
20181582
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12942-6
7809151
Brain Res Brain Res Rev. 1999 Jan;29(1):83-120
9974152
Pharmacol Ther. 2005 Jan;105(1):69-84
15626456
Neuron. 2005 Apr 7;46(1):89-102
15820696
J Physiol. 1993 Dec;472:615-63
7908327
Prog Neurobiol. 2002 Oct;68(3):167-207
12450487
J Physiol. 2008 Jun 1;586(11):2695-712
18388134
J Neurosci Methods. 2006 Jun 30;154(1-2):1-18
16554092
Cereb Cortex. 2004 Jul;14(7):748-58
15054054
J Neurophysiol. 1997 Sep;78(3):1468-75
9310436
J Neurosci. 1998 May 1;18(9):3386-403
9547246
J Physiol. 1999 Apr 1;516 ( Pt 1):227-48
10066937
Neuroscience. 2005;136(4):1003-14
16226383
J Physiol. 2002 Feb 1;538(Pt 3):773-86
11826164
Neuron. 1994 Feb;12(2):261-9
8110457
Curr Opin Neurobiol. 2009 Jun;19(3):245-53
19559598
Trends Neurosci. 2003 Nov;26(11):631-40
14585604
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12450-5
14519849
Neuropharmacology. 1996 Jun;35(6):637-42
8887973
Neuroscience. 2007 Aug 10;148(1):7-21
17630217
Hippocampus. 2010 Sep;20(9):1003-9
19830814
Neurosci Lett. 1996 Mar 22;207(1):70-2
8710213
Neuron. 2000 Mar;25(3):663-72
10774733
J Neurophysiol. 1998 Jun;79(6):2903-10
9636096
Neuroscience. 2000;98(3):407-27
10869836