Modeling of the neurodynamic mechanisms of acetylcholine regulation of memory storage and recall

Oscillations supported by the medial septum are considered to be a key mechanism for learning and memory, but the specific kinetic mechanisms by which they modulate the memory storage and recall functions of the hippocampal CA1 region via acetylcholine (ACh) have not been deeply revealed. Therefore, in this study, we constructed a highly biomimetic microcircuit model of the hippocampal CA1 region, including pyramidal cells, axo-axonic cells, basket cells, bistratified cells, and oriens-lacunosum moleculare cells, which are rich in multicompartmental morphology and complex synaptic connections. Meanwhile, the model integrated network inputs from the entorhinal cortex, CA3 Schaffer lateral branches and medial septal nucleus. Further, the present study assessed in detail the modulatory effects of ACh on the hippocampal CA1 network by analyzing the peak power, peak frequency, and recall quality of sum oscillations under different synaptic connectivity strengths of ACh vs GABA_A. The results showed that moderate ACh input enhanced the oscillatory synchronization of pyramidal neurons by precisely regulating the excitation-inhibition balance of interneurons, which was conducive to the formation of LTP synaptic plasticity and the enhancement of recall efficiency; on the contrary, excessive input led to the excessive inhibitory effect of interneurons on pyramidal neuron discharge, which then disrupted the normal synchronization of the sum oscillations and ultimately significantly reduced the hippocampal CA1 area’s storage and recall functions. In conclusion, this study reveals the dual regulatory role of ACh in the dynamic balance of excitation-inhibition in the CA1 area, which provides a new modeling tool and theoretical basis for understanding the mechanism of memory storage and recall.