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

Nat Commun. 2021 Jan 18;12(1):413. doi: 10.1038/s41467-020-20523-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / physiology*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Excitatory Postsynaptic Potentials / physiology*
  • Long-Term Potentiation / physiology*
  • Male
  • Memory, Long-Term / physiology
  • Patch-Clamp Techniques
  • Rats
  • Receptors, AMPA / metabolism*
  • Theta Rhythm / physiology


  • Receptors, AMPA
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2