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Naji, M. |
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Motta, Antonella |
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Aletan, Dirar |
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Mohamed, Tarek |
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Ertürk, Emre |
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Taccardi, Nicola |
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Petrov, R. H. | Madrid |
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Alshaaer, Mazen | Brussels |
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Bih, L. |
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Casati, R. |
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Kočí, Jan | Prague |
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Kalteremidou, Kalliopi-Artemi | Brussels |
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Azam, Siraj |
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Ospanova, Alyiya |
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Blanpain, Bart |
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Ali, M. A. |
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Popa, V. |
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Rančić, M. |
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Ollier, Nadège |
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Azevedo, Nuno Monteiro |
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Landes, Michael |
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Rignanese, Gian-Marco |
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Bessa-Neto, Diogo
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document
Synapse specific and plasticity-regulated AMPAR mobility tunes synaptic integration
Abstract
<jats:title>Abstract</jats:title><jats:p>Synaptic responses adapt to fast repetitive inputs during bursts of neuronal network activity over timescales of milliseconds to seconds, either transiently facilitating or depressing. This high-frequency stimulus-dependent short-term synaptic plasticity (HF-STP) relies on a number of molecular processes that collectively endow synapses with filtering properties for information processing, optimized for the transmission of certain input frequencies and patterns in distinct circuits<jats:sup>1–3</jats:sup>. Changes in HF-STP are traditionally thought to stem from changes in pre-synaptic transmitter release<jats:sup>1,2</jats:sup>, but post-synaptic modifications in receptor biophysical properties or surface diffusion also regulate HF-STP<jats:sup>4–11</jats:sup>. A major challenge in understanding synapse function is to decipher how pre- and post-synaptic mechanisms synergistically tune synaptic transmission efficacy during HF-STP, and to determine how neuronal activity modifies post-synaptic signal computation and integration to diversify neuronal circuit function. Here, taking advantage of new molecular tools to directly visualize glutamate release<jats:sup>12</jats:sup>and specifically manipulate the surface diffusion of endogenous AMPAR in intact circuits<jats:sup>13</jats:sup>, we define the respective contributions of pre-synaptic glutamate release, AMPAR desensitization and surface mobility to frequency-dependent synaptic adaptation. We demonstrate that post-synaptic gain control and signal integration capacity in synaptic networks is influenced by synapse-specific differences in AMPAR desensitization and diffusion-trapping characteristics that are shaped by molecular signaling events recruited during LTP.</jats:p>