P208 Integration of a Purkinje cell model including morphological details with a bidirectional synaptic plasticity model
Takeki Mukaida*1, Kaaya Akira1, Tadashi Yamazaki1
1Graduate School of Informatics and Engineering, The University of Electro-Communications, Tokyo, Japan
*Email: takeki.mukaida@gmail.com
Introduction
Most neurons have large dendrites that span in space, on which various active ion channels are implemented. On the dendrites, synapses undergo plasticity depending on the postsynaptic membrane potential and calcium ion concentration. However, how the potential and concentration that can diffuse across dendrites affect the plasticity remains unresolved. To address this question, we used a multi-compartment Purkinje cell model that includes morphological details [1] and a biologically accurate plasticity model [2], and integrated them. Then, we performed a numerical simulation to examine the relationship between the spatial location and the directions of plastic change of synapses.
Methods
We used a multi-compartment Purkinje cell (PC) model, which comprises 1600 compartments classified into four types (soma, main dendrite, small dendrite, and spiny dendrite) [2]. To this model, we added compartments that represent spines. On each spine, we implemented a bidirectional synaptic plasticity model, composed of 18 differential equations, based on calcium ion concentration [1]. Sole activation of parallel fibers (PFs) increases the concentration slightly, resulting in long-term potentiation (LTP), whereas pained activation with a climbing fiber (CF) increases it largely, resulting in long-term depression (LTD).
Results
The maximum amplitude of excitatory postsynaptic currents (EPSCs) in each spine was investigated when PF and CF stimulation were applied. Spine compartments were attached to all 9 compartments of main dendrites and 165 compartments of smooth and spiny dendrites were randomly selected. PF stimulation was applied to all spines at 8 pulses of 150 Hz per second, whereas CF stimulation was applied only to the main dendrites at one pulse per second. After 300 seconds of stimulation, the maximum amplitude of EPSCs in each spine was measured. We observed that the maximum amplitude was lower than the initial value in spines close to the main dendrite but exceeded the initial value in spines far from the main dendrite (Fig. 1).
Discussion
The present result suggests that the direction of plasticity depends on the spatial location of the dendrites. Thus, the spatial location of spines that underwent either LTD or LTP implies the formation of clusters of spines that have the same direction of the plastic change. This may contribute to enhance the learning capability of a single neuron by harnessing the spatial distinction of the spines distributed across dendrites. Therefore, we will investigate whether neurons can use spatial shapes to realize complex learning such as pattern recognition and separation, while we will also incorporate experimental results to further enhance the learning capability.
Figure 1. Fig 1. The maximum amplitude of EPSCs in each spine after 300 seconds of stimulation.
AcknowledgementsThis study was supported by MEXT KAKENHI Grant Number JP22H05161.
References
● Pinto, T. M., Schilstra, M. J., Roque, A. C., & Steuber, V. (2020). Binding of Filamentous Actin to CaMKII as Potential Regulation Mechanism of Bidirectional Synaptic Plasticity by β CaMKII in Cerebellar Purkinje Cells. Scientific reports, 10(1), 9019. https://doi.org/10.1038/s41598-020-65870-9
● De Schutter, E., & Bower, J. M. (1994). An active membrane model of the cerebellar Purkinje cell. I. Simulation of current clamps in slice. Journal of neurophysiology, 71(1), 375–400. https://doi.org/10.1152/jn.1994.71.1.375