Calcium-dependent but action potential-independent BCM-like metaplasticity in the hippocampus.
The Bienenstock, Cooper and Munro (BCM) computational model, which incorporates a metaplastic sliding threshold for LTP induction, accounts well for experience-dependent changes in synaptic plasticity in the visual cortex. BCM-like metaplasticity over a shorter timescale has also been observed in the hippocampus, thus providing a tractable experimental preparation for testing specific predictions of the model. Here, using extracellular and intracellular electrophysiological recordings from acute rat hippocampal slices, we tested the critical BCM predictions (1) that high levels of synaptic activation will induce a metaplastic state that spreads across dendritic compartments, and (2) that postsynaptic cell-firing is the critical trigger for inducing that state. In support of the first premise, high-frequency priming stimulation inhibited subsequent long-term potentiation and facilitated subsequent long-term depression at synapses quiescent during priming, including those located in a dendritic compartment different to that of the primed pathway. These effects were not dependent on changes in synaptic inhibition or NMDA/metabotropic glutamate receptor function. However, in contrast to the BCM prediction, somatic action potentials during priming were neither necessary nor sufficient to induce the metaplasticity effect. Instead, in broad agreement with derivatives of the BCM model, calcium as released from intracellular stores and triggered by M1 muscarinic acetylcholine receptor activation was critical for altering subsequent synaptic plasticity. These results indicate that synaptic plasticity in stratum radiatum of CA1 can be homeostatically regulated by the cell-wide history of synaptic activity through a calcium-dependent but action potential-independent mechanism.
Brain Health Research Centre and Department of Psychology, University of Otago, Dunedin 9054, New Zealand. email@example.com
SourceThe Journal of neuroscience : the official journal of the Society for Neuroscience 32:20 2012 May 16 pg 6785-94
CA1 Region, Hippocampal
Calcium Channels, L-Type
Long-Term Synaptic Depression
Receptor, Muscarinic M1
Receptors, Metabotropic Glutamate
Pub Type(s)In Vitro
Research Support, Non-U.S. Gov't