PT - JOURNAL ARTICLE AU - Divyansh Mittal AU - Rishikesh Narayanan TI - Resonating neurons stabilize heterogeneous grid-cell networks AID - 10.1101/2020.12.10.419200 DP - 2021 Jan 01 TA - bioRxiv PG - 2020.12.10.419200 4099 - http://biorxiv.org/content/early/2021/07/20/2020.12.10.419200.short 4100 - http://biorxiv.org/content/early/2021/07/20/2020.12.10.419200.full AB - A central theme that governs the functional design of biological networks is their ability to sustain stable function despite widespread parametric variability. Here, we investigated the impact of distinct forms of biological heterogeneities on the stability of a two-dimensional continuous attractor network (CAN) implicated in grid-patterned activity generation. We show that increasing degrees of biological heterogeneities progressively disrupted the emergence of grid- patterned activity and resulted in progressively large perturbations in low-frequency neural activity. We postulated that targeted suppression of low-frequency perturbations could ameliorate heterogeneity-induced disruptions of grid-patterned activity. To test this, we introduced intrinsic resonance, a physiological mechanism to suppress low-frequency activity, either by adding an additional high-pass filter (phenomenological) or by incorporating a slow negative feedback loop (mechanistic) into our model neurons. Strikingly, CAN models with resonating neurons were resilient to the incorporation of heterogeneities and exhibited stable grid-patterned firing. We found CAN networks with mechanistic resonators to be more effective in targeted suppression of low-frequency activity, with the slow kinetics of the negative feedback loop essential in stabilizing these networks. As low-frequency perturbations (1/f noise) are pervasive across biological systems, our analyses suggest a universal role for mechanisms that suppress low- frequency activity in stabilizing heterogeneous biological networks.Competing Interest StatementThe authors have declared no competing interest.