title: Presynaptic modulation by metabotropic glutamate receptors of excitatory and inhibitory synaptic inputs to hypothalamic magnocellular neurons.
abstract: The effects of activation of metabotropic glutamate receptors (mGluRs) on synaptic inputs to magnocellular neurons of the hypothalamic supraoptic nucleus (SON) were studied with the use of whole cell patch-clamp and microelectrode recordings in acute hypothalamic slices. Application of the mGluR agonist trans-(+/-)-1-amino-1,3-cyclopentane dicarboxylic acid (trans-ACPD, 100 microM) elicited an increase in the frequency of spontaneous excitatory postsynaptic potentials (EPSPs) and excitatory postsynaptic currents (EPSCs) in 20% of the cells, and of spontaneous inhibitory postsynaptic potentials (IPSPs) and inhibitory postsynaptic currents (IPSCs) in 50% of the cells tested in normal medium. The increased frequency of spontaneous EPSPs/EPSCs and IPSPs/IPSCs was blocked by tetrodotoxin (TTX), indicating that mGluRs act to excite the somata/dendrites of presynaptic glutamatergic and GABAergic neurons. (RS)-3,5-dihydroxyphenylglycine (50 microM), a selective group I receptor agonist, mimicked the presynaptic somatic/dendritic effects of trans-ACPD, suggesting that the presynaptic somatic/dendritic receptors responsible for increased spike-dependent glutamate and gamma-aminobutyric acid (GABA) release belong to the group I mGluRs. In the presence of TTX, trans-ACPD caused a decrease in the frequency of miniature EPSCs (up to 90%) in 13 of 16 cells, and a decrease in the frequency of miniature IPSCs (up to 80%) in 10 of 16 cells tested. Miniature EPSC and IPSC amplitudes usually did not change in trans-ACPD, suggesting that activation of metabotropic receptors located at presynaptic glutamatergic and GABAergic terminals led to a reduction in transmitter release onto SON magnocellular neurons. L(+)-2-amino-4-phosphonobutyric acid (100-250 microM), a selective group III receptor agonist, mimicked the effects of trans-ACPD at presynaptic terminals, decreasing the frequency of miniature EPSCs and IPSCs by up to 85% without affecting their amplitude. Thus the metabotropic receptors at presynaptic glutamate and GABA terminals in the SON belong to group III mGluRs. EPSCs evoked by electrical stimulation were enhanced by the group III receptor antagonist (S)-2-amino-2-methyl-4-phosphonobutanoic acid, suggesting that presynaptic metabotropic receptors are activated by the release of endogenous glutamate. These data indicate that mGluRs in the hypothalamus have opposing actions at presynaptic somata/dendrites and at presynaptic terminals. Activation of group I receptors (mGluR1 and/or mGluR5) on presynaptic somata/dendrites led to an increase in spike-dependent transmitter release, whereas activation of the group III receptors (mGluR4, 7, and/or 8) on presynaptic terminals suppressed glutamate and GABA release onto SON neurons. No differences were seen in the effects of mGluR activation between immunohistochemically identified oxytocin and vasopressin neurons of the SON.
authors.affiliation: Neuroscience Training Program, Tulane University, New Orleans, Louisiana 70118, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Schrader
authors.forename: J G
authors.initials: JG
authors.lastname: Tasker
mesh_terms: D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology*
chemical_list: D018696:Neuroprotective Agents; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane