A Computational Analysis of Circuit Motifs in the Hippocampus

Abstract

Pyramidal cells (PC) in the hippocampal subregion Cornu Ammonis area 3 (CA3) receive projections from two predominant pathways: one from stellate cells (SC) in the medial entorhinal cortex layer II (MECLII) and one from granule cells (GC) in the dentate gyrus (DG). These projections create two unique information streams for CA3. The first stream involves SCs directly contacting PCs, and the second is an indirect stream where SCs contact GCs, which in turn contact PCs. Each PC and GC are contacted by 1500 SCs, and each PC by 80 GCs. However, it is unclear if the interactions between these cell types form circuit-specific motifs, and how they might affect PC activity. Our experiments delved into the connectivity of these interactions through simulations in the GPU-based simulation environment CARLsim, with a network model of 10,000 SCs, 80 GCs, and one PC. The PC and GCs received random input from SCs that simulated the activity of these cells in vivo. We first tested and verified the no motif (null) hypothesis that approximately 15% of the 1500 SCs that contact each GC also contact a PC (PC-contacting SCs) and the remaining 85% from those that do not (non-PC-contacting SCs). We then ran subsequent experiments that varied this balance between PC-contacting SCs and non-PC-contacting SCs from 0 to 100%. The resultant PC activity was then analyzed in MATLAB. In the no motif network, the PC exhibited a mean firing frequency of 0.4 Hz, consistent with this cell type’s mean firing frequency in vivo. Changing the balance between PC-contacting SCs and non-PC-contacting SCs from 0 to 100% revealed a maximal PC mean firing rate of 0.7 Hz at 80% PC-contacting and 20% non-PC-contacting-SCs. Furthermore, the mean firing frequency increased between 0 and 80% for PC-contacting SCs and decreased between 80 and 100%. Future work will explore why changing the balance in these circuit-specific motifs produces these PC firing frequency trends.