It is well documented that synapses play a significant role in the transmission of
information between neurons in the brain. However, in the absence of synaptic transmission,
neural activity has been observed to continue to propagate. Several experimental results
have shown that propagation of epileptiform activity in rodent hippocampi propagates
at a speed of ∼0.1 m/s. This observed activity in the 4-AP model propagates independently
of synaptic transmission and gap junctions, and is outside the range of ionic diffusion
and axonal conduction speeds. Compartment modeling of pyramidal neurons indicate that
ephaptic coupling, or endogenous electric fields, could be responsible for this propagation
of neural activity in pathological conditions such as epilepsy. Recent studies suggest
electric fields can activate neighboring neurons, thereby generating a self-propagating
wave. However, there is no experimental data suggesting ephaptic coupling is necessary
and sufficient for spontaneous, self-regenerating propagation of neural activity.
Using in vitro and in vivo electrophysiology in combination with imaging of trans-membrane
voltages using genetically encoded voltage indicators, we test the hypothesis that
ephaptic coupling is a critical mechanism for non-synaptic neural propagation. We
have developed a novel extracellular electric field clamp capable of measuring the
endogenous field and generate an "anti" field to block non-synaptic spontaneous propagation
in the rodent hippocampus (Figure 1A). By blocking propagation, we are able to show
that ephaptic coupling is a necessary mechanism for propagation of spontaneous activity.
Finally, since electric fields propagate as volume conductors, we test if activity
can propagate through a complete physical cut of the tissue, thereby eliminating all
other forms of close cell-to-cell communication and showing that electric fields alone
are sufficient to mediate non-synaptic propagation. Preliminary results suggest that
spontaneous epileptiform activity propagates by triggering the activity on the other
side across the cut with ephaptic coupling without changing the speed (Figure 1B).
Our findings suggest that ephaptic coupling is necessary and sufficient to mediate
non-synaptic neural propagation. Further investigation of this mechanism could explain
how focal seizures appear to start abruptly and unpredictably, and how the rare micro-seizures
of human partial epilepsy (seizure-like events that are not clinically detectable
and are resistant to most common antiepileptic drugs) propagate through the hippocampus
and cortex. Furthermore, endogenous electric fields could play an important role in
brain function and could provide an explanation for unresolved mechanisms of deep
brain stimulation or transcranial direct current stimulation (tDCS).
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© 2018 Published by Elsevier Inc.