Abstract

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.

Links

Publisher Full Text

Authors

Hulme SR, Jones OD, Ireland DR, Abraham WC

Institution

Brain Health Research Centre and Department of Psychology, University of Otago, Dunedin 9054, New Zealand. hulme@psy.otago.ac.nz

Source

The Journal of neuroscience : the official journal of the Society for Neuroscience 32:20 2012 May 16 pg 6785-94

MeSH

Action Potentials
Animals
Atropine
CA1 Region, Hippocampal
Calcium
Calcium Channels, L-Type
Long-Term Potentiation
Long-Term Synaptic Depression
Male
Models, Neurological
Muscarinic Antagonists
Neural Inhibition
Neuronal Plasticity
Pirenzepine
Rats
Rats, Sprague-Dawley
Receptor, Muscarinic M1
Receptors, Metabotropic Glutamate
Receptors, N-Methyl-D-Aspartate
Synaptic Potentials

Pub Type(s)

In Vitro
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22593048