An activity-dependent spermine-mediated mechanism that modulates glutamate transmission.

on the tissue being considered. In the present case of the mossy fiber–granule cell glomerulus, spillover augments excitability by activating receptors at neighboring synapses and, therefore, increases the reliability of transmission. In addition, because adjacent granule cells presumably all sense spillover, it might help to synchronize the activity of multiple granule cells. In other tissues, however, spillover can inhibit neighboring synapses by activating presynaptic metabotropic receptors [17] or can cause prolonged depolarizations of postsynaptic cells by activating postsynaptic metabotropic receptors [18]. The two papers highlighted here illustrate that MVR and spillover can both occur. Which of these two mechanisms dominates at a given synapse will depend on several morphological and physiological characteristics , including release probability, intersynaptic distance and the density of surrounding glutamate transporters. Heresy or not, these mechanisms seem to be here to stay. Multivesicular release at single functional synaptic sites in cerebellar stellate and basket cells. Analysis of multiquantal transmitter release from single cultured cortical neuron terminals. pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics. Neuronal glutamate transporters limit activation of NMDA receptors by neurotransmitter spillover on CA1 pyramidal cells. Spillover of glutamate onto synaptic AMPA receptors enhances fast transmission at a cerebellar synapse. A developmental switch in neurotransmitter flux enhances synaptic efficacy by affecting AMPA receptor activation. Use-dependent increases in glutamate concentration activate presynaptic metabotropic glutamate receptors. Neuronal glutamate transporters control activation of postsynaptic metabotropic glutamate receptors and influence cerebellar long-term depression. Intracellular polyamines are responsible for inward rectification of Ca 21-permeable AMPA receptors and, hence, exert a voltage-dependent block upon these channels. In a recently described mechanism, neuronal activation modulates the synthesis of polyamines to regulate the amount of Ca 21 flux and the excitability threshold at developing synapses that contain poly-amine-sensitive AMPA receptors. The polyamines putrescine, spermidine and spermine are present in almost all cells. These organic polycations appear to play important roles in protein synthesis, cell growth and cell differentiation, and their synthesis and degradation are tightly controlled by several enzymes that are regulated by cellular activity [1]. Polyamines are protonated at physiological pH and can interact with several intracellular targets, including nucleic acids and proteins. In the past few years, the specific interactions between polyamines, in particular spermine, and several functionally diverse ion channels have been described [2]. Spermine blocks the channel pore of inward-rectifier K þ channels from the intracellular side, controlling the resting …