PKA drives an increase in AMPA receptor unitary conductance during LTP in the hippocampus

Pojeong Park, John Georgiou, Thomas M. Sanderson, Kwang-Hee Ko, Heather Kang, Ji-il Kim, Clarrisa A. Bradley, Zuner A. Bortolotto, Min Zhuo, Bong-Kiun Kaang and Graham L. Collingridge ()
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Pojeong Park: University of Bristol
John Georgiou: Mount Sinai Hospital
Thomas M. Sanderson: University of Bristol
Kwang-Hee Ko: Seoul National University
Heather Kang: University of Bristol
Ji-il Kim: Seoul National University
Clarrisa A. Bradley: Seoul National University
Zuner A. Bortolotto: University of Bristol
Min Zhuo: Seoul National University
Bong-Kiun Kaang: Seoul National University
Graham L. Collingridge: University of Bristol

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Long-term potentiation (LTP) at hippocampal CA1 synapses can be expressed by an increase either in the number (N) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors or in their single channel conductance (γ). Here, we have established how these distinct synaptic processes contribute to the expression of LTP in hippocampal slices obtained from young adult rodents. LTP induced by compressed theta burst stimulation (TBS), with a 10 s inter-episode interval, involves purely an increase in N (LTPN). In contrast, either a spaced TBS, with a 10 min inter-episode interval, or a single TBS, delivered when PKA is activated, results in LTP that is associated with a transient increase in γ (LTPγ), caused by the insertion of calcium-permeable (CP)-AMPA receptors. Activation of CaMKII is necessary and sufficient for LTPN whilst PKA is additionally required for LTPγ. Thus, two mechanistically distinct forms of LTP co-exist at these synapses.

Date: 2021
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DOI: 10.1038/s41467-020-20523-3

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