Cell-class-specific electric field entrainment of neural activity

The authors of this study demonstrated that neurons can be influenced by sinusoidal electric fields, exhibiting robust entrainment behavior. This phenomenon, referred to as synchronization or entrainment, polarizes the cell membrane subthreshold across different neuronal cell types and is both cell-class-specific and dependent on stimulation frequency. The authors observed this entrainment across various brain regions and species. Because the field strength in their experiments (∼1–25 mV/mm) is comparable to that measured in vivo, their results can also shed light on cellular entrainment due to endogenous fields, i.e., via ephaptic coupling.

The study highlights that, in the cortices of rodents and humans, neurons show synchronization dependent on the frequency of the stimulus and the neuronal cell type. For example, excitatory pyramidal neurons, which have slower firing rates, entrain to both slow and fast electric fields. In contrast, fast-spiking inhibitory neuron classes such as Pvalb and Sst primarily phase-lock to fast fields.

The study further discusses how coordinated neuronal circuit activity generates extracellular electric fields, which can be measured, especially in cortical structures. These fields, while typically weak, are not always confined locally; their spatial diffusion depends on the coherence and geometry of the sources. The authors suggest that the interaction between these fields and neurons offers a potential form of non-synaptic communication. Although for the authors these fields are generally not strong enough to trigger neuronal firing, they can, in the presence of synaptic drive, modulate spike timing and enhance coordination between local spiking and oscillations in various bands of the local field potential.

However, evidence from additional research challenges the authors' assertion that synaptic drive is necessary for neuronal activity influenced by electric fields. Ex vivo experiments using hippocampal slices confirmed that waves can propagate across physical voids in neural tissue, provided the gap does not exceed 400 µm, as the field strength diminishes according to the inverse-square law. Similar preliminary results in vivo with mice demonstrated that neural activity can traverse complete transverse cuts of the hippocampus (Chiang et al., 2019; Shivacharan et al., 2019). These findings indicate that endogenous fields, previously considered too weak to excite nearby neurons, can in fact be strong enough to do so.