Figure 3.

Bioelectric pathways

(A) The hardware that enables complex computations in neuronal networks consists of ion channel proteins that determine cells’ electrical state and gap junctions (electrical synapses) that selectively propagate this state to their neighbors. (B) This hardware is evolutionarily ancient and ubiquitous, enabling similar (albeit slower) dynamics in non-neuronal cells. Taking advantage of this bioelectrical interface to the circuits that make anatomical decisions has significant biomedical implications. For example, normal brain development in the tadpole model (C) requires a specific bioelectrical prepattern in the nascent anterior ectoderm. Disrupting this pattern with a range of teratogens or via mutations of the NOTCH protein results in severe brain defects and a loss of learning behaviors (D). Remarkably, correct brain structure, gene expression, and learning rates can be reinstated (E) when the correct bell-curve-shaped bioelectric prepattern (F) is enforced according to a computational model that suggests specific drugs that target ion channels to enforce the correct bioelectric prepattern (G).¹⁴⁹ (F) shows the effect of various manipulations on embryonic bioelectric prepattern: control (blue), microinjection with voltage-gated potassium channel (Kv1.5, red), microinjection with glycine-gated chloride channel (GlyR, purple), and microinjection with GlyR plus ivermectin treatment (IVM; green). (A) and (B) are courtesy of Jeremy Guay and are taken with permission from Levin.³⁰ (C)–(E) are courtesy of Vaibhav Pai. (F) is taken with permission from Pai et al.¹⁵⁰ (G) is courtesy of Alexis Pietak.¹⁵¹.