Timing-dependent septal cholinergic induction of dynamic hippocampal synaptic plasticity

Neuron. 2011 Jul 14;71(1):155-65. doi: 10.1016/j.neuron.2011.04.026.


Cholinergic modulation of hippocampal synaptic plasticity has been studied extensively by applying receptor agonists or blockers; however, the effect of rapid physiological cholinergic stimuli on plasticity is largely unknown. Here, we report that septal cholinergic input, activated either by electrical stimulation or via an optogenetic approach, induced different types of hippocampal Schaffer collateral (SC) to CA1 synaptic plasticity, depending on the timing of cholinergic input relative to the SC input. When the cholinergic input was activated 100 or 10 ms prior to SC stimulation, it resulted in α7 nAChR-dependent long-term potentiation (LTP) or short-term depression, respectively. When the cholinergic stimulation was delayed until 10 ms after the SC stimulation, a muscarinic AChR-dependent LTP was induced. Moreover, these various forms of plasticity were disrupted by Aβ exposure. These results have revealed the remarkable temporal precision of cholinergic functions, providing a novel mechanism for information processing in cholinergic-dependent higher cognitive functions.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amyloid beta-Peptides / pharmacology
  • Animals
  • Choline O-Acetyltransferase / genetics
  • Choline O-Acetyltransferase / physiology
  • Cholinergic Fibers / drug effects
  • Cholinergic Fibers / physiology*
  • Dose-Response Relationship, Drug
  • Electric Stimulation / methods
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / drug effects
  • Hippocampus / physiology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Photic Stimulation / methods
  • Rats
  • Rats, Wistar
  • Receptors, Muscarinic / physiology
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / physiology
  • Septum of Brain / drug effects
  • Septum of Brain / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Time Factors
  • alpha7 Nicotinic Acetylcholine Receptor


  • Amyloid beta-Peptides
  • Chrna7 protein, human
  • Chrna7 protein, mouse
  • Chrna7 protein, rat
  • Receptors, Muscarinic
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • Choline O-Acetyltransferase