Abstract
BackgroundKnowledge of how synapses alter their efficiency of communication is central to the understanding of learning and memory. The most extensively studied forms of synaptic plasticity are long-term potentiation (LTP) and its counterpart long-term depression (LTD) of AMPA receptor-mediated synaptic transmission. In the CA1 region of the hippocampus, it has been shown that LTP often involves a rapid increase in the unitary conductance of AMPA receptor channels. However, LTP can also occur in the absence of any alteration in AMPA receptor unitary conductance. In the present study we have used whole-cell dendritic recording, failures analysis and non-stationary fluctuation analysis to investigate the mechanism of depotentiation of LTP.ResultsWe find that when LTP involves an increase in unitary conductance, subsequent depotentiation invariably involves the return of unitary conductance to pre-LTP values. In contrast, when LTP does not involve a change in unitary conductance then depotentiation also occurs in the absence of any change in unitary conductance, indicating a reduction in the number of activated receptors as the most likely mechanism.ConclusionsThese data show that unitary conductance can be bi-directionally modified by synaptic activity. Furthermore, there are at least two distinct mechanisms to restore synaptic strength from a potentiated state, which depend upon the mechanism of the previous potentiation.
Highlights
Knowledge of how synapses alter their efficiency of communication is central to the understanding of learning and memory
In the present study we have investigated a second form of long-term depression (LTD) known as depotentiation (DP), which is a reversal of pre-established long-term potentiation (LTP) [24,25,26,27]
We find a reciprocal relationship between LTP and DP, such that DP of LTPγ invariably involves a restoration of the pre-LTP γ (DPγ) whereas DP of LTPN never involves a change in γ (DPN)
Summary
Knowledge of how synapses alter their efficiency of communication is central to the understanding of learning and memory. Fast excitatory synaptic transmission in the central nervous system, which is mediated predominantly by the AMPA subtype of glutamate receptors, can undergo longterm bi-directional modifications in strength [1,2,3]. These persistent changes have been proposed to be key synaptic processes involved in learning and memory. It has been shown that LTP can involve a rapid increase in γ of existing AMPA receptors [18] This could be caused by a Ca2+/calmodulinkinase II (CaM-KII)-mediated phosphorylation of GluR1 which occurs during LTP [19], and which causes an increase in γ of GluR1 homomers in transfected cells [20].
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