Degeneracy in the robust expression of spectral selectivity, subthreshold oscillations, and intrinsic excitability of entorhinal stellate cells

Mittal, Divyansh and Narayanan, Rishikesh (2018) Degeneracy in the robust expression of spectral selectivity, subthreshold oscillations, and intrinsic excitability of entorhinal stellate cells. In: JOURNAL OF NEUROPHYSIOLOGY, 120 (2). pp. 576-600.

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Abstract

Biological het- erogeneities are ubiquitous and play critical roles in the emergence of physiology at multiple scales. Although neurons in layer II (LII) of the medial entorhinai cortex (MEC) express heterogeneities in channel properties, the impact of such heterogeneities on the robustness of their cellular-scale physiology has not been assessed. Here, we performed a 55-parameter stochastic search spanning nine voltage- or calcium-activated channels to assess the impact of channel heterogeneities on the concomitant emergence of 10 in vitro electrophysiological characteristics of LII stellate cells (SCs). We generated 150,000 models and found a heterogeneous subpopulation of 449 valid models to robustly match all electrophysio logical signatures. We employed this heterogeneous population to demonstrate the emergence of cellular-scale degeneracy in 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 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-scalcefficient 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 cellularscale physiology despite significant channel heterogeneities, and forms an efficacious substrate for evaluating the impact of biological heterogeneities on entorhinai network function. NEW & NOTEWORTHY We assessed the impact of heterogeneities in channel properties on the robustness of cellular-scale physiology of medial entorhinai cortical stellate neurons. We demonstrate that neuronal models with disparate channel combinations were endowed with similar physiological characteristics, as a consequence of the many-to-many mapping between channel properties and the physiological characteristics that they modulate. We predict that the spike-triggered average of stellate cells should be endowed with theta-frequency spectral selectivity and fast gamma-band coincidence detection capabilities.

Item Type:	Journal Article
Publication:	JOURNAL OF NEUROPHYSIOLOGY
Publisher:	AMER PHYSIOLOGICAL SOC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
Additional Information:	Copy right for this article belong to AMER PHYSIOLOGICAL SOC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	30 Aug 2018 15:42
Last Modified:	30 Aug 2018 15:42
URI:	http://eprints.iisc.ac.in/id/eprint/60529

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