Sinusoidal stimulation on afferent fibers can selectively activate different types of neurons in rat hippocampus

Deep brain stimulation (DBS) is a promising therapy for treating various brain disorders. Although narrow electrical pulses have been commonly used by DBS, sinusoidal waveforms have also been investigated to improve the effects of DBS therapy and to save electrical energy. However, the effect of sinusoidal stimulation on neurons is unclear yet. To investigate the modulation of sinusoidal stimulation on different types of neurons in networks, sinusoidal stimulations (50 Hz) with lower-intensity and higher-intensity were applied to the afferent axons (Schaffer collaterals) in rat hippocampal CA1 region. The firing of inhibitory interneurons and excitatory pyramidal cells (the principal neurons of CA1) during the stimulations were detected and were compared with their baseline firing before stimulations. Results showed that sinusoidal stimulation with a lower-intensity (~30 μA) can selectively activate the interneurons thereby suppressing the firing of pyramidal cells in the downstream post-synaptic region. However, sinusoidal stimulation with a higher-intensity (~60 μA) can increase the firing of both types of neurons significantly. Presumably, the two different effects of inhibition and excitation on the principal neurons by different stimulation intensities could be caused by the fact that the firing threshold of interneurons is lower than that of pyramidal cells. The results provide important clues for selective modulation of neuronal activity by brain stimulations thereby developing different stimulation paradigms to treat various brain disorders.