Differential Regulation of Synaptic Inputs to Dentate Hilar Border Interneurons by Metabotropic Glutamate Receptors

1998 ◽  
Vol 79 (6) ◽  
pp. 2903-2910 ◽  
Author(s):  
James Doherty ◽  
Raymond Dingledine

Doherty, James and Raymond Dingledine. Differential regulation of synaptic inputs to dentate hilar border interneurons by metabotropic glutamate receptors. J. Neurophysiol. 79: 2903–2910, 1998. Regulation of synaptic transmission by metabotropic glutamate receptors (mGluRs) was examined at two excitatory inputs to interneurons with cell bodies at the granule cell–hilus border in hippocampal slices taken from neonatal rats. Subgroup-selective mGluR agonists altered the reliability, or probability of transmitter release, of evoked minimal excitatory synaptic inputs and decreased the amplitudes of excitatory postsynaptic currents (EPSCs) evoked with conventional stimulation. The group II–selective agonist, (2S,1R′,2R′,3R′)-2-(2,3-dicarboxylcyclopropyl) glycine (DCG-IV; 1 μM), reversibly depressed the reliability of EPSCs evoked by stimulation of the dentate granule cell layer. However, DCG-IV had no significant effect on EPSCs evoked by CA3 stimulation in the majority (82%) of hilar border interneurons. Both the group III–selective agonist, l-(+)-2-amino-4-phosphonobutyric acid (l-AP4; 3 μM), and the group I–selective agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG; 20 μM) reversibly depressed synaptic input to interneurons from both CA3 and the granule cell layer. We conclude that multiple pharmacologically distinct mGluRs presynaptically regulate synaptic transmission at two excitatory inputs to hilar border interneurons. Further, the degree of mGluR-meditated depression of excitatory drive is greater at synapses from dentate granule cells onto interneurons than at synapses from CA3 pyramidal cells.

1997 ◽  
Vol 77 (4) ◽  
pp. 1889-1905 ◽  
Author(s):  
Scott C. Molitor ◽  
Paul B. Manis

Molitor, Scott C. and Paul B. Manis. Evidence for functional metabotropic glutamate receptors in the dorsal cochlear nucleus. J. Neurophysiol. 77: 1889–1905, 1997. The parallel fibers (PFs) of the dorsal cochlear nucleus (DCN) molecular layer use glutamate as a neurotransmitter. Although metabotropic glutamate receptors (mGluRs) have been identified on cells postsynaptic to the PFs, little is known about the effects of mGluR activation in PF synaptic transmission in the DCN. To investigate these effects, PF-evoked field potentials were recorded from the DCN in guinea pig brain stem slice preparations. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated components of the field response were reversibly depressed by bathing the slice in the mGluR agonists (±)-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD) or (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD]. A similar depression was produced by the mGluR1/5 agonist (RS)-3,5-dihydroxyphenylglycine, but not by the mGluR2/3 agonist (2S,1′S,2′S)-2-(carboxycyclopropyl)glycine or by the mGluR4/6/7/8 agonist l(+)-2-amino-4-phosphonobutyric acid. In addition to the AMPA component, an N-methyl-d-aspartate (NMDA) receptor-dependent component of the field potentials could be identified when the slices were bathed in a low magnesium solution. Under these conditions, the ACPD-induced depression of the AMPA component did not completely recover, whereas the depression of the NMDA component usually recovered and potentiated in some slices. Intracellular recordings of PF-evoked responses were obtained to ascertain which neuronal populations were affected by mGluR activation. Activation of mGluRs produced a reversible depression of PF-evoked responses in cartwheel cells that was not accompanied by any changes in paired-pulse facilitation. The PF-evoked responses recorded from pyramidal cells were unaffected by mGluR activation. Both cell types exhibited a reversible depolarization during (1S,3R)-ACPD application. Subsequent experiments explored the involvement of protein kinases in mediating the effects of mGluRs. The protein kinase C (PKC) activator phorbol-12,13-diacetate partially inhibited the mGluR-mediated depression of the field response;however, the PKC inhibitor 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimide or the protein kinaseA inhibitor N-[2-(( p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide had little effect on the actions of (1S,3R)-ACPD. These results demonstrate that functional mGluRs are present at PF synapses and are capable of modulating PF synaptic transmission in the DCN.


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