Transmitter release at most central synapses depends on multiple types of calcium channels. Identification of the channels mediating GABA release in hippocampus is complicated by the heterogeneity of interneurons. Unitary IPSPs were recorded from pairs of inhibitory and pyramidal cells in hippocampal slice cultures. The N-type channel antagonist omega-conotoxin MVIIA abolished IPSPs generated by interneurons in st. radiatum, whereas the P/Q-type antagonist omega-agatoxin IVA had no effect. In contrast, omega-agatoxin IVA abolished IPSPs generated by st. lucidum and st. oriens interneurons, but omega-conotoxin MVIIA had no effect. After unitary IPSPs were blocked by toxin, transmission could not be restored by increasing presynaptic calcium entry. The axons of the two types of interneurons terminated within distinct strata of area CA3. Thus, GABA release onto pyramidal cells, unlike glutamate release, is mediated entirely by either N- or P-type calcium channels, depending on the presynaptic cell and the postsynaptic location of the synapse.

1. The effects of metabotropic glutamate receptor (mGluR) activation on synaptic inhibition were examined using whole-cell recordings of spontaneous and miniature inhibitory synaptic currents from CA3 pyramidal cells in rat hippocampal slices.2. The mGluR agonist (1S, 3R)trans-i-aminocyclopentane-1,3-dicarboxylic acid (tACPD) increased spontaneous IPSC (spIPSC) frequency by up to 5-fold. At doses above 5/AM the increase was transient (15-45 s) and was followed by a decline to control frequency. In these conditions, elevating external K+ from 2 to 8 mm could still increase spIPSC frequency.3. Miniature IPSCs (mIPSCs) were recorded in the presence of 1 UM TTX, 5 iM Mg2+ and nominally zero Ca2+. At concentrations above 50/uM, tACPD induced a sustained, reversible reduction in mIPSC frequency by up to 43 %. 4. Quisqualate, at doses as low as 50 nM, increased spIPSC frequency, but did not affect mIPSC frequency at concentrations up to 10 /M. 5. The specific mGluR2 and 3 agonist (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV, 3/#M) reduced mIPSC frequency by 40+4% but did not increase spIPSC frequency. 6. The putative mGluR antagonist L-2-amino-3-phosphonopropionate (L-AP3, 1 mM) blocked the effect of tACPD on mIPSC but not spIPSC frequency. The broad-spectrum antagonist (RS)-a-methyl-4-carboxyphenylglycine (MCPG, 500 /M) blocked both responses. 7. mGluR activation also had dual effects on IPSCs evoked by focal extracellular stimulation.Application of 5,uM tACPD increased the mean amplitude of evoked IPSCs by 112 + 9%, largely by reducing the proportion of response failures. In contrast, IPSC amplitude was reduced to 44 + 1 % of control values by 3/M DCG-IV. 8. These results suggest hippocampal inhibitory cells express two distinct mGluR subtypes.One receptor (possibly mGluRi or 5) is located on somato-dendritic membrane and enhances cell excitability. Another (mGluR2 or 3) is present at inhibitory terminals and reduces the probability of GABA release.

SUMMARY1. Inhibitory cell activity and inhibitory postsynaptic potentials impinging spontaneously on pyramidal cells were recorded in the CA3 region of hippocampal slices from guinea-pig. We compared the effects on synaptic inhibition, of tetanic stimuli in the presence of antagonists of ionotropic excitatory amino acid receptors, and of application of agonists of metabotropic glutamate receptors.2. Tetanic stimulation of afferent fibres caused an increase, of duration 0 52-5 min, in the frequency of spontaneous Cl--mediated IPSPs. Inhibitory cell firing increased due to a depolarization and a reduction of after-hyperpolarizing potentials.3. Tetanic stimulation induced, in some experiments, rhythmic bursts of IPSPs and transformed the firing pattern of some inhibitory cells from a discharge of single action potentials to rhythmic bursts of three to five action potentials.4. Application of the metabotropic glutamate receptor agonist, trans-1-aminocyclopentane-1,3-dicarboxylic acid (tACPD), at concentrations from 3-10/,M increased the frequency of spontaneous IPSPs. In some slices tACPD caused IPSPs to occur rhythmically. IPSP

Paired recordings from monosynaptically connected CA3 interneurons and pyramidal cells of rat hippocampal slice cultures were used to compare the modulation of GABA release at synapses from distinct interneurons. The group II metabotropic glutamate receptor (mGluR) agonist (2S,2′R,3′R)‐2‐(2′,3′‐dicarboxylcyclopropyl) glycine (DCG‐IV, 5 μm) reduced the amplitude of IPSPs originating from stratum radiatum but not stratum oriens interneurons. In contrast, the GABAB receptor agonist (‐)baclofen (10 μm) reduced the amplitude of unitary IPSPs elicited by all interneurons. IPSPs mediated by stratum oriens interneurons were unaffected by the N‐type calcium channel blocker ω‐conotoxin MVIIA (1 μm) but were suppressed by the P/Q‐type blocker ω‐agatoxin IVA (200 nm). In contrast, IPSPs mediated by stratum radiatum interneurons were abolished by ω‐conotoxin MVIIA. Transmission dynamics were different at synapses from the two groups of interneurons. IPSPs mediated by stratum oriens interneurons showed marked paired‐pulse depression (PPD) at intervals of 50–400 ms. IPSPs mediated by stratum radiatum interneurons showed paired‐pulse facilitation (PPF) at 50 ms and PPD at longer intervals. The amplitude of unitary IPSPs from all interneurons was unaffected by the GABAB receptor antagonist CGP52432 (2 μm) as was PPD at both 50 and 400 ms intervals. However, CGP52432 did reduce PPD of extracellularly evoked IPSPs. Our results show that two groups of inhibitory synapses impinging onto CA3 pyramidal cells can be distinguished according to their dynamic and modulatory properties.