piperidines and philanthotoxin-343

Dentate gyrus granule cells innervate inhibitory interneurons via a continuum of synapses comprised of either Ca(2+)-impermeable (CI) or Ca(2+)-permeable (CP) AMPA receptors. Synapses at the extreme ends of this continuum engage distinct postsynaptic responses, with activity at CI synapses being strongly influenced by NMDA receptor activation. NMDARs at CI synapses have a lower NR2B subunit composition and a higher open probability, which generate larger amplitude and more rapid EPSCs than their CP counterparts. A novel form of NMDAR-dependent long-term depression (iLTD) is associated with CI-mossy fiber synapses, whereas iLTD at CP synapses is dependent on Ca(2+)-permeable AMPA receptor activation. Induction of both forms of iLTD required elevation of postsynaptic calcium. Thus mossy fibers engage CA3 interneurons via multiple synapse types that will act to expand the computational repertoire of the mossy fiber-CA3 network.

Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Anticonvulsants; Calcium; Chlorides; Cyclopropanes; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Glycine; Hippocampus; In Vitro Techniques; Interneurons; Mossy Fibers, Hippocampal; N-Methylaspartate; Patch-Clamp Techniques; Phenols; Piperidines; Polyamines; Protein Subunits; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission; Valine

NMDA receptor stimulation concomitantly increases the release of [14C]acetylcholine and [3H]-spermidine from rat striatal slices in vitro. The NMDA-induced release of both acetylcholine and spermidine was blocked with equal potency by the NMDA channel blocker phencyclidine (0.1-10 microM). However, certain other channel blockers, including dextromethorphan (1-100 microM), which antagonized NMDA-evoked acetylcholine release without affecting NMDA-evoked spermidine release, and dextrorphan (1-100 microM) and memantine (1-100 microM), which block NMDA-evoked acetylcholine release more potently than NMDA-evoked spermidine release, showed greater selectivity of action. As previously shown for ifenprodil, eliprodil (SL82.0715; 1-100 microM) blocked NMDA-evoked acetylcholine but not spermidine release. This selectivity is also observed for other agents interacting with the polyamine site(s) on the NMDA receptor, including arcaine (1-1,000 microM), philanthotoxin343, and argiotoxin636 (10 microM) and was also noted for desipramine (1-100 microM). The NMDA-induced release of acetylcholine and spermidine is likely to be mediated by different native NMDA receptor subtypes, and several NMDA antagonists may be candidates for a selective action at a particular NMDA receptor subtype.

Topics: Acetylcholine; Animals; Corpus Striatum; Desipramine; Dextromethorphan; Indoleacetic Acids; N-Methylaspartate; Phenols; Phenylacetates; Piperidines; Polyamines; Rats; Receptors, N-Methyl-D-Aspartate; Spermidine; Spider Venoms