Title:
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Plasticity of NMDA receptor-mediated transmission and metaplasticity in the CA1 region of the hippocampus
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The hippocampus is a key structure of the brain for learning and memory
processes. Two inputs to the CA1 region, the Schaffer collateral (SC) and
the temporoammonic (TA) pathways, have different roles in these
processes.
N-methyl-D-aspartate receptors (NMDAR) are crucial for induction of
synaptic plasticity and learning and memory processes, and are
themselves subject to plasticity. Plasticity of NMDAR-mediated
transmission can therefore change the threshold for induction of future
synaptic plasticity and affect learning and memory. However, little is
known about the effect of NMDAR-mediated plasticity on subsequent longterm
potentiation (L TP) and long-term depression (L TO).
In this study a combination of whole-cell recordings from CA1 pyramidal
neurons and field recordings in the CA 1 area of the hippocampus was
used to show that the SC-CA 1 input is subject to metaplasticity whereas
the TA-CA1 input is not. Indeed L TO of NMDAR-mediated transmission is
selectively induced in the SC pathway but not in the TA pathway. This LTD
of NMDA EPSCs can prevent subsequent induction of L TP of AMPA
receptor-mediated transmission via an increase of the threshold. The L TO
of NMDAR-mediated transmission was shown to be mGlu1 receptor-dependent.
However, LTD of AMPAR-mediated transmission in both
inputs was not affected by the prior induction of L TO of NMDAR-mediated
transmission.
Therefore, these results show that the SC-CA 1 input can undergo
meta plasticity whereas the TA-CA 1 input does not. These differences
could explain the distinct roles of the two inputs in memory.
In some neurodegenerative diseases such as Alzheimer's disease ,(AD)
memory is impaired. AD is a tauopathy characterized by the aggregation
of AB, a derivative of amyloid precursor protein (APP), and Tau, a
microtubule-associated protein, which lead to synaptic loss and neuronal
degeneration.
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