Synchronization of pacemaker cell firing by weak ELF fields: simulation by a circuit model

Entrainment of output action potentials from repetitively firing pacemaker cells, brought about by regularly spaced excitatory or inhibitory postsynaptic inputs, is a well-known phenomenon. Synchronization of neural firing patterns by extremely low frequency (ELF) external electric fields has also been observed. Whereas current densities of approximately 10 A-m(-2) are required for direct excitation of otherwise quiescent neural tissue, much lower peak current densities (approximately 10[-2] A-m2) have been reported to entrain spontaneously firing molluscan pacemaker cells. We have developed a neural spike generator circuit model that simulates repetitive spike generation by a space clamped patch (area approximately 10[-7] m2) of excitable membrane subjected to depolarizing current. Picoampere (pA) range variation of DC depolarizing current causes a corresponding smooth variation of neural spike frequency, producing a physiologically realistic stimulus-response (S-R) characteristic. When lower pA range 60 Hz AC current is superposed upon the DC depolarizing current, smooth variation of the S-R characteristic is distorted by subharmonic locking of the spike generator at 30, 20, 15, 12, 10 Hz, and higher order subharmonic frequencies. Although the additional superposition of a physiologically realistic level of "white" current noise, covering the bandwidth 4-200 Hz, suffices to obscure higher order subharmonic locking, locking at 30, 20, and 15 Hz is still clearly evident in the presence of noise. Subharmonic locking is observed at an root mean square AC simulated tissue current density of approximately 10(-5) A-m(-2).