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Sci. Signal., 19 July 2011
Vol. 4, Issue 182, p. ec195
[DOI: 10.1126/scisignal.4182ec195]

EDITORS' CHOICE

Synaptic Plasticity Finding the Right Time for a Change

Elizabeth M. Adler

Science Signaling, AAAS, Washington, DC 20005, USA

Long-term changes in the efficacy of glutamatergic synapses between hippocampal Schaffer collaterals (SC) and CA1 pyramidal neurons have provided a widely studied cellular model of learning and memory. CA1 neurons also receive input from medial septal neurons that use acetylcholine (ACh). Dysfunctions in cholinergic signaling have been implicated in disorders that affect cognitive function, including Alzheimer’s disease (AD), and exogenous ACh modulates CA1 synaptic plasticity induced by high-frequency stimulation (see Berg). Gu and Yakel paired individual stimuli to the SC with stimuli to the stratum oriens (SO, to activate septal cholinergic inputs) and analyzed excitatory postsynaptic currents (EPSCs) in CA1 neurons in rat hippocampal slices. They found that the timing of cholinergic input was crucial to the response: With 10 pairs of stimuli delivered at 0.033 Hz, electrical stimulation of the SO 100 ms before that of the SC elicited long-term potentiation (LTP) of EPSC amplitude, whereas stimulation of the SO 10 ms before the SC elicited short-term depression (STD). Concurrent stimulation failed to affect the size of the EPSC, and stimulation of the SO 10 ms after that of the SC elicited LTP. Similar results were obtained in experiments using slices from mice in which the light-activated channel channelrhodopsin was selectively expressed in cholinergic neurons in medial septal nuclei, so that the cholinergic inputs to CA1 could be stimulated with laser illumination. Pharmacological analysis indicated that LTP or STD elicited by activation of cholinergic inputs before SC stimulation was mediated by α7 nicotinic ACh receptors (α7 nAChRs), whereas LTP elicited by cholinergic activation after SC stimulation depended on muscarinic AChRs (mAChRs), conclusions substantiated by analyses of mice lacking the α7 nAChR. Intiguingly, pre-exposure to a low-concentration (10 nM) β-amyloid peptide (Aβ), which has been implicated in cognitive dysfunction in AD, blocked plastic changes mediated by the α7 nAChR, with much higher concentrations (complete blockade at 1 µM) blocking mAChR-mediated LTP. Thus, the authors conclude that the exact timing of a modulatory cholinergic signal is crucial to its effects on synaptic plasticity and that disruption of cholinergic modulation of plasticity could provide a mechanism for Aβ to impair cognitive function.

Z. Gu, J. L. Yakel, Timing-dependent septal cholinergic induction of dynamic hippocampal synaptic plasticity. Neuron 71, 155–165 (2011). [PubMed]

D. K. Berg, Timing is everything, even for cholinergic control. Neuron 71, 6–8 (2011). [PubMed]

Citation: E. M. Adler, Finding the Right Time for a Change. Sci. Signal. 4, ec195 (2011).


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