Influence of the Endogenous Acetylcholine on STDP Induction

Abstract

Cholinergic inputs from the medial septum are projected to pyramidal neurons in hippocampal CA1 and release acetylcholine (ACh) from their terminals. The cholinergic inputs are considered to be integrated with sensory inputs and to play a crucial role in learning and memory. Meanwhile, it has been reported that the relative timing between pre- and post-synaptic spiking determines the direction and extent of synaptic changes in a critical temporal window, called Spike Timing-Dependent Plasticity (STDP). The positive and negative pairing-timing of a post-synaptic spike for pre-synaptic spikes induce long-term potentiation (LTP) and long-term depression (LTD), respectively.

To investigate influence of muscarinic activation by cholinergic inputs on synaptic plasticity, STDP induction-protocol was applied during the muscarinic induction of a slow excitatory postsynaptic potential (slow EPSP) following by a repetitive stimulation in the stratum oriens. As a result, LTP induced with the positive timing was facilitated and LTD induced with the negative timing was abolished by the muscarinic activation, respectively. Furthermore, interestingly, LTD was switched to LTP, depending on the intensity of ACh changed by application of eserine, a cholinesterase inhibitor. It suggests that synaptic plasticity is modulated depending on cholinergic inputs. The modulation of synaptic plasticity by muscarinic activation may shows one important stage of the integration of top-down and bottom-up information integration in hippocampal CA1 neurons.