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AMPA receptors gate spine Ca(2+) transients and spike-timing-dependent potentiation.

ABSTRACT: Spike timing-dependent long-term potentiation (t-LTP) is the embodiment of Donald Hebb's postulated rule for associative memory formation. Pre- and postsynaptic action potentials need to be precisely correlated in time to induce this form of synaptic plasticity. NMDA receptors have been proposed to detect correlated activity and to trigger synaptic plasticity. However, the slow kinetic of NMDA receptor currents is at odds with the millisecond precision of coincidence detection. Here we show that AMPA receptors are responsible for the extremely narrow time window for t-LTP induction. Furthermore, we visualized synergistic interactions between AMPA and NMDA receptors and back-propagating action potentials on the level of individual spines. Supralinear calcium signals were observed for spike timings that induced t-LTP and were most pronounced in spines well isolated from the dendrite. We conclude that AMPA receptors gate the induction of associative synaptic plasticity by regulating the temporal precision of coincidence detection.

SUBMITTER: Holbro N

PROVIDER: S-EPMC2936625 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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AMPA receptors gate spine Ca(2+) transients and spike-timing-dependent potentiation.

Holbro Niklaus N Grunditz Asa A Wiegert J Simon JS Oertner Thomas G TG

Proceedings of the National Academy of Sciences of the United States of America 20100823 36

Spike timing-dependent long-term potentiation (t-LTP) is the embodiment of Donald Hebb's postulated rule for associative memory formation. Pre- and postsynaptic action potentials need to be precisely correlated in time to induce this form of synaptic plasticity. NMDA receptors have been proposed to detect correlated activity and to trigger synaptic plasticity. However, the slow kinetic of NMDA receptor currents is at odds with the millisecond precision of coincidence detection. Here we show that ...[more]

PMID: 20798031

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Project description:Ca(2+) influx via GluR2-lacking Ca(2+)-permeable AMPA glutamate receptors (CP-AMPARs) can trigger changes in synaptic efficacy in both interneurons and principle neurons, but the underlying mechanisms remain unknown. We took advantage of genetically altered mice with no or reduced GluR2, thus allowing the expression of synaptic CP-AMPARs, to investigate the molecular signaling process during CP-AMPAR-induced synaptic plasticity at CA1 synapses in the hippocampus. Utilizing electrophysiological techniques, we demonstrated that these receptors were capable of inducing numerous forms of long-term potentiation (referred to as CP-AMPAR dependent LTP) through a number of different induction protocols, including high-frequency stimulation (HFS) and theta-burst stimulation (TBS). This included a previously undemonstrated form of protein-synthesis dependent late-LTP (L-LTP) at CA1 synapses that is NMDA-receptor independent. This form of plasticity was completely blocked by the selective CP-AMPAR inhibitor IEM-1460, and found to be dependent on postsynaptic Ca(2+) ions through calcium chelator (BAPTA) studies. Surprisingly, Ca/CaM-dependent kinase II (CaMKII), the key protein kinase that is indispensable for NMDA-receptor dependent LTP at CA1 synapses appeared to be not required for the induction of CP-AMPAR dependent LTP due to the lack of effect of two separate pharmacological inhibitors (KN-62 and staurosporine) on this form of potentiation. Both KN-62 and staurosporine strongly inhibited NMDA-receptor dependent LTP in control studies. In contrast, inhibitors for PI3-kinase (LY294002 and wortmannin) or the MAPK cascade (PD98059 and U0126) significantly attenuated this CP-AMPAR-dependent LTP. Similarly, postsynaptic infusion of tetanus toxin (TeTx) light chain, an inhibitor of exocytosis, also had a significant inhibitory effect on this form of LTP. These results suggest that distinct synaptic signaling underlies GluR2-lacking CP-AMPAR-dependent LTP, and reinforces the recent notions that CP-AMPARs are important facilitators of synaptic plasticity in the brain.

Dataset Information

AMPA receptors gate spine Ca(2+) transients and spike-timing-dependent potentiation.

Publications

AMPA receptors gate spine Ca(2+) transients and spike-timing-dependent potentiation.

Similar Datasets

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