Spike timing amplifies the effect of electric fields on neurons: implications for endogenous field effects.
Despite compelling phenomenological evidence that small electric fields (<5 mV/mm) can affect brain function, a quantitative and experimentally verified theory is currently lacking. Here we demonstrate a novel mechanism by which the nonlinear properties of single neurons "amplify" the effect of small electric fields: when concurrent to suprathreshold synaptic input, small electric fields can have significant effects on spike timing. For low-frequency fields, our theory predicts a linear dependency of spike timing changes on field strength. For high-frequency fields (relative to the synaptic input), the theory predicts coherent firing, with mean firing phase and coherence each increasing monotonically with field strength. Importantly, in both cases, the effects of fields on spike timing are amplified with decreasing synaptic input slope and increased cell susceptibility (millivolt membrane polarization per field amplitude). We confirmed these predictions experimentally using CA1 hippocampal neurons in vitro exposed to static (direct current) and oscillating (alternating current) uniform electric fields. In addition, we develop a robust method to quantify cell susceptibility using spike timing. Our results provide a precise mechanism for a functional role of endogenous field oscillations (e.g., gamma) in brain function and introduce a framework for considering the effects of environmental fields and design of low-intensity therapeutic neurostimulation technologies.
Radman
Thomas
T
Department of Biomedical Engineering, City College of the City University of New York, New York, New York 10031, USA.
Su
Yuzhuo
Y
An
Je Hi
JH
Parra
Lucas C
LC
Bikson
Marom
M
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods*; D008297:Male; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors