Polyamine-dependent facilitation of postsynaptic AMPA receptors counteracts paired-pulse depression

At many glutamatergic synapses in the brain, calcium-permeable alpha - amin o - 3 - hydro - 5 - methyl - 4 - isoxazolepropionate receptor (AMPAR) chann els mediate fast excitatory transmission(1-6). These channels are blocked b y endogenous intracellular polyamines(7-9), which are found in virtually ev ery type of cell(10,11). In excised patches, use-dependent relief of polyam ine block enhances glutamate-evoked currents through recombinant and native calcium-permeable, polyamine-sensitive AMPAR channels(12). The contributio n of polyamine unblock to synaptic currents during high-frequency stimulati on may be to facilitate currents and maintain current amplitudes in the fac e of a slow recovery from desensitization or presynaptic depression(12,13). Here we show, on pairs and triples of synaptically connected neurons in sl ices, that this mechanism contributes to short-term plasticity in local cir cuits formed by presynaptic pyramidal neurons and postsynaptic multipolar i nterneurons in layer 2/3 of rat neocortex, Activity-dependent relief from p olyamine block of postsynaptic calcium-permeable AMPARs in the interneurons either reduces the rate of paired-pulse depression in a frequency-dependen t manner or, at a given stimulation frequency, induces facilitation of a sy naptic response that would otherwise depress. This mechanism for the enhanc ement of synaptic gain appears to be entirely postsynaptic.