Glia-mediated modulation of extracellular potassium concentration determines the sexually dimorphic output frequency of a model brainstem oscillator

Sexual dimorphism in behavior is widespread among animals, but the cellular mechanisms underlying neural control of this phenomenon are largely unknown. One behavior that has provided some important clues about how such sex differences might develop is the electric organ discharge of Apteronotus leptorhynchus. In this weakly electric fish, the mean discharge frequencies of males and females are 880 Hz and 740 Hz, respectively, with little overlap of the two frequency bands. The discharges are controlled, in a one-to-one fashion, by the neural oscillations of the pacemaker nucleus in the medulla oblongata. Experimental evidence has shown that the astrocytic syncytium associated with the neural network that generates these oscillations is significantly larger, and stronger coupled via gap junctions, in females than in males. In the present study, modeling of this network was performed to test the hypotheses that the sex-dependent differences in the structure and properties of the astrocytic syncytium mediate better buffering of extracellular potassium in females than in males, which in turn causes, via a lowering of the potassium equilibrium potential, a decrease in the oscillation frequency. Simulations of the neural activity of the pacemaker nucleus and its individual components demonstrated that under both spontaneous and induced conditions the oscillation frequency and the potassium equilibrium potential are strongly positively correlated. These simulations predict that sufficient separation of the electric organ discharge frequencies for establishment of the sexual dimorphism can be achieved by rather minor alterations in the concentration of the extracellular potassium concentration in the pacemaker nucleus. (C) 2019 Elsevier Ltd. All rights reserved.