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.
Highlights
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)
The best-characterized form of LTP occurs at the Schaffer collateral-commissural pathway (SCCP) in the hippocampus, where it is triggered by synaptic activation of NMDA (N-methylD-aspartate) receptors[4] and is expressed as a persistent increase in AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor-mediated synaptic transmission[5]
We found that the compressed theta burst stimulation (TBS) protocol resulted exclusively in LTPN, for which calmodulin-dependent kinase II (CaMKII) was both necessary and sufficient
Summary
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). The best-characterized form of LTP occurs at the Schaffer collateral-commissural pathway (SCCP) in the hippocampus, where it is triggered by synaptic activation of NMDA (N-methylD-aspartate) receptors[4] and is expressed as a persistent increase in AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor-mediated synaptic transmission[5]. This modification is primarily due to a functional modulation of AMPA receptors (AMPARs), which may involve a change in the number of active channels (N) (termed LTPN) and/or their single-channel conductance (γ) properties (termed LTPγ) (e.g.6–9). Since the PKA-dependent form of LTP requires de novo protein synthesis and has stimulation features similar to spaced behavioural learning, LTPγ is likely to underlie the formation of synaptic engrams and long-term memory
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