Showing papers by "Massimo Scanziani published in 1993"

Presynaptic inhibition of excitatory synaptic transmission mediated by alpha adrenergic receptors in area CA3 of the rat hippocampus in vitro

Abstract: We have investigated the action of norepinephrine (NE) on excitatory synaptic transmission in the hippocampus by recording from CA3 pyramidal cells in organotypic slice cultures. NE (5 microM) was found to decrease the amplitude of pharmacologically isolated EPSPs elicited with stimulation of mossy fibers or recurrent axon collaterals (mean decrease in EPSP amplitude, 44%). Desensitization was observed with repetitive applications. NE did not affect the sensitivity of CA3 cells to iontophoretically applied AMPA, and did not affect the amplitude distribution of TTX-resistant, miniature excitatory synaptic currents. These data suggest that NE acts at presynaptic receptors to decrease glutamate release. This action of NE was blocked by the alpha receptor antagonist phentolamine and the specific alpha 1 receptor antagonist prazosine, but not by the beta receptor antagonist timolol or the alpha 2 receptor antagonist idazoxan. Inhibition of EPSPs by NE was prevented by pretreatment of cultures with pertussis toxin, indicating that G- proteins couple these receptors to their effectors. Stimulation of protein kinase C with phorbol ester blocked the action of NE on EPSPs. This effect, as well as the desensitization of NE responses, was reduced by application of the protein kinase inhibitor staurosporin. Presynaptic inhibition of excitatory synaptic transmission, mediated by alpha adrenergic receptors, represents a novel modulatory action of NE in the hippocampus.

Preo'naptic inhibition in the hippocampu$

Abstract: Presynaptic receptors for virtually all transmitters have been identified throughout the nervous system. Recent studies in the hippocampus provide new insights into the mechanisms by which the activation of these receptors leads to presynaptic inhibition of transmitter release, and characterize the second messengers involved in coupling presynaptic receptors to their effectors. Pre- synaptic receptors also provide a tractable route via which the amount of transmitter release may be selectively regulated in therapeutically useful ways. Transmitter release is elicited by the influx of Ca 2+ through voltage-dependent channels that are acti- vated when an action potential invades the axon ter- minal. Elevated intraterminal Ca e + concentrations then increase the probability that transmitter-containing vesicles will fuse with the presynaptic membrane and release their contents into the synaptic cleft. Transmitter release at a given synapse is not con- stant, but rather is subject to a variety of modulatory influences that can either increase or decrease the probability of release. More than 35 years ago, Frank and Fuortes 1 presented the first evidence for pre- synaptic inhibition of synaptic transmission at Ia afferents to spinal motoneurons. We now know that there are receptors for neurotransmitters, at or near the presynaptic terminals of many synapses, whose activation can change the likelihood that a presynaptic action potential will successfully result in transmitter release. Surprisingly, all transmitters examined to date produce presynapfic inhibition in the hippo- campus, and there are, to our knowledge, no examples of transmitters that produce presynaptic facilitation in this structure, although evidence is accumulating for a facilitory action of several putative retrograde messengers 2, a. Considerable progress has been made in identifying the neurotransmitters mediating pre- synaptic inhibition, defining their receptors pharmaco- logically, characterizing their second messenger sys- tems and elucidating their effector mechanisms. The hippocarnpus provides a convenient and well-studied model system with which to illustrate several im- portant principles of presynaptic inhibition, focusing on three presynaptic receptors that have been best characterized: adenosine A1, ~-opioid and GABAB receptors. Although data from many hippocampal preparations are discussed, the illustrations are taken from our own work using cultured hippocampal slices, which combine the advantages of cell culture with the preservation of the organotypic cytoarchitecture 4.