CELL-TYPE SPECIFIC SENSING AND CONTROL OF FIRING RATE STATISTICS

Neurons possess synaptic and intrinsic plasticity mechanisms that homeostatically regulate spiking activity, maintaining functionality despite physiological perturbations [1-4]. Extensive evidence implicates mean intracellular Calcium concentration as a key variable that is sensed by homeostatic mechanisms. This enables regulation of mean firing rate [5] but is believed to be insufficient to maintain firing rate variance, which is required to ensure sensitivity to fluctuating input [6]. Since regulation of higher-order statistics of spiking activity requires these quantities to be tracked, multiple sensing mechanisms have been proposed to control spiking statistics [7,8]. However, to date, no corresponding cellular pathways have been found.

We demonstrate that mean Calcium concentration alone is sufficient to produce a simple readout of higher-order statistics of spiking activity. Using conductance based models under various input conditions, we show time-averaged intracellular Calcium concentration strongly correlates with firing rate mean and variance in individual neurons. Using these inferred relationships, we demonstrate a simple Calcium-based feedback loop that compensates for disturbances in the input statistics to jointly regulate firing rate mean and variance.

We show that cell-type specific mixtures of membrane ionic conductances lead to classes of homeostatic "personalities'' that respond distinctly to changes in input statistics. Neurons can tune intrinsic parameters such as maximal conductances to modulate the implicit relationship between rate statistics. Therefore, the pairs of correlates that determine feasible statistics and the homeostatic response of a cell are not fixed. Our results provide a parsimonious account of sensing and control mechanisms tied together by cellular identity.

References:

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