Nonlinear analysis of neuronal firing modulated by sinusoidal stimulation at axons in rat hippocampus

Electrical stimulation of the brain has shown promising prospects in treating various brain diseases. Although biphasic pulse stimulation remains the predominant clinical approach, there has been increasing interest in exploring alternative stimulation waveforms, such as sinusoidal stimulation, to improve the effectiveness of brain stimulation and to expand its application to a wider range of brain disorders. Despite this growing attention, the effects of sinusoidal stimulation on neurons, especially on their nonlinear firing characteristics, remains unclear.

To address the question, 50 Hz sinusoidal stimulation was applied on Schaffer collaterals of the rat hippocampal CA1 region in vivo. Single unit activity of both pyramidal cells and interneurons in the downstream CA1 region was recorded and analyzed. Two fractal indexes, namely the Fano factor and Hurst exponent, were used to evaluate changes in the long-range correlations, a manifestation of nonlinear dynamics, in spike sequences of neuronal firing.

The results demonstrate that sinusoidal electrical stimulation increased the firing rates of both pyramidal cells and interneurons, as well as altered their firing to stimulation-related patterns. Importantly, the sinusoidal stimulation increased, rather than decreased the scaling exponents of both Fano factor and Hurst exponent, indicating an increase in the long-range correlations of both pyramidal cells and interneurons.

The results firstly reported that periodic sinusoidal stimulation without long-range correlations can increase the long-range correlations of neurons in the downstream post-synaptic area. These results provide new nonlinear mechanisms of brain sinusoidal stimulation and facilitate the development of new stimulation modes.