Calcium-permeable AMPA receptors mediate timing-dependent LTP elicited by 6 coincident action potentials at Schaffer collateral-CA1 synapses

Autor: Cepeda-Prado, Efrain A., Khodaie, Babak, Quiceno, Gloria D., Beythien, Swantje, Leßmann, Volkmar, Edelmann, Elke
Jazyk: angličtina
Rok vydání: 2019
Předmět:
DOI: 10.1101/719633
Popis: Activity-dependent synaptic plasticity in neuronal circuits represents a cellular model of memory formation. Such changes can be elicited by repeated high-frequency stimulation inducing long-term potentiation (LTP), or by low frequency stimulation induced long-term depression (LTD). Spike timing-dependent plasticity (STDP) can induce equally robust long-lasting timing-dependent LTP (t-LTP) in response to low frequency repeats of coincident action potential (AP) firing in presynaptic cells followed by postsynaptic neurons. Conversely, this stimulation can lead to t-LTD if the postsynaptic spike precedes the presynaptic action potential. STDP is best suited to investigate synaptic plasticity mechanisms at the single cell level. Commonly, STDP paradigms relying on 25-100 repeats of coincident pre- and postsynaptic firing are used to elicit t-LTP or t-LTD. However, the minimum number of repeats required for successful STDP induction, which could account for fast single trial learning in vivo , is barely explored. Here, we examined low repeat STDP at Schaffer collateral-CA1 synapses by pairing one presynaptic AP with either one postsynaptic AP (1:1 t-LTP) or a burst of 4 APs (1:4 t-LTP). We found 3-6 repeats to be sufficient to elicit t-LTP. Postsynaptic Ca 2+ elevation for 1:1 t-LTP required NMDARs and VGCCs, while 1:4 t-LTP depended on metabotropic GluR and ryanodine receptor signaling. Surprisingly, both 6x t-LTP variants were strictly dependent on activation of postsynaptic Ca 2+ -permeable AMPARs. Both t-LTP forms were regulated differentially by dopamine receptors, but occurred independent from BDNF/TrkB signaling. Our data show that synaptic changes induced by only 3-6 repeats of mild STDP stimulation occuring in ≤10 s can take place on time scales observed also during single trial learning.
Databáze: OpenAIRE