Degeneracy in the robust expression of spectral selectivity, subthreshold oscillations and intrinsic excitability of entorhinal stellate cells
Authors: Mittal Divyansh , Narayanan Rishikesh 
Published: October 2017

ABSTRACTBiological heterogeneities are ubiquitous and play critical roles in the emergence of physiology at multiple scales. Although neurons in layer II (LII) of the medial entorhinal cortex (MEC) express heterogeneities in their channel properties, the impact of such heterogeneities on the robustness of cellular-scale physiology has not been assessed. Here, we performed a 55-parameter stochastic search spanning 9 voltage- or calcium-activated channels to assess the impact of channel heterogeneities on the concomitant emergence of 10 electrophysiological characteristics of LII stellate cells (SCs). We generated 50,000 models and found a heterogeneous subpopulation of 155 valid models to robustly match all electrophysiological signatures. We employed this heterogeneous population to demonstrate the emergence of cellular-scale degeneracy in LII SCs, whereby disparate parametric combinations expressing weak pairwise correlations resulted in similar models. We then assessed the impact of virtually knocking out each channel from all valid models and demonstrate that the mapping between channels and measurements was many-to-many, a critical requirement for the expression of degeneracy. Finally, we quantitatively predict that the spike-triggered average of LII SCs should be endowed with theta-frequency spectral selectivity and coincidence detection capabilities in the fast gamma-band. We postulate this fast gamma-band coincidence detection as an instance of cellular-scale efficient coding, whereby SC response characteristics match the dominant oscillatory signals in LII MEC. The heterogeneous population of valid SC models built here unveils the robust emergence of cellular-scale physiology despite significant channel heterogeneities, and forms an efficacious substrate for evaluating the impact of biological heterogeneities on entorhinal network function.KEY POINTSStellate cells (SC) in layer II (LII) of the medial entorhinal cortex express cellular-scale degeneracy in the concomitant manifestation of several of their unique physiological signatures.Several disparate parametric combinations expressing weak pairwise correlations resulted in models with very similar physiological characteristics, including robust theta-frequency membrane potential oscillations spanning several levels of subthreshold depolarization.Electrophysiological measurements of LII SCs exhibited differential and variable dependencies on underlying channels, and the mapping between channels and measurements was many-to-many.Quantitative predictions point to theta-frequency spectral selectivity and fast gamma-range coincidence detection capabilities in class II/III spike-triggered average of LII SCs, with the postulate for this to be an instance of cellular-scale efficient coding.A heterogeneous cell population that accounts for both channel and intrinsic heterogeneities in LII SCs, which could be employed by network models of entorhinal function to probe the impact of several biological heterogeneities on spatial navigation circuits.