Backpropagating action potentials (bpAPs) are retrograde electrical signals crucial for modulating synaptic plasticity. They play a pivotal role in regulating neuronal computation and memory formation. In dentate gyrus granule cells, which are key neuronal populations responsible for pattern separation and memory storage, bpAPs-mediated signaling is particularly important for integrating synaptic inputs and fine-tuning network activity. However, this neuronal population has marked structural and functional heterogeneity, including regular granule cells (GCs), semilunar granule cells (SGCs), and hilar ectopic granule cells (HEGCs). The influence of the distinct biophysical properties of these GC subtypes on backpropagation dynamics such as attenuation amplitude, velocity, and spatial spread remains unclear. Here, we utilized multi-compartment models of three types of GCs to systematically investigate the backpropagation efficiency across three metrics: attenuation amplitude, attenuation rate, and propagation distance. We found that higher dendritic K ${}^{+}$ channel density drove strong attenuation of bpAPs in SGCs (highest rate, shortest propagation), whereas higher dendritic Na ${}^{+}$ channel density in HEGCs minimized attenuation. Dendritic branching patterns modulated attenuation amplitude secondarily, while passive axial resistance had negligible effects. These findings establish dendritic active properties rather than morphology as the dominant regulator of attenuation intensity and reveal how activity regulation in these neuronal subtypes contributes to pattern separation and memory storage.

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.