Alterations in ion channel expression surrounding implanted microelectrode arrays in the brain

Abstract

Microelectrode arrays designed to map and modulate neuronal circuitry have enabled greater understanding and treatment of neurological injury and disease. Reliable detection of neuronal activity over time is critical for the successful application of chronic recording devices. Here, we assess device-related plasticity by exploring local changes in ion channel expression and their relationship to device performance over time. We investigated four voltage-gated ion channels (Kv1.1, Kv4.3, Kv7.2, and Nav1.6) based on their roles in regulating action potential generation, firing patterns, and synaptic efficacy. We found that a progressive increase in potassium channel expression and reduction in sodium channel expression accompanies signal loss over 6 weeks (both LFP amplitude and number of units). This motivated further investigation into a mechanistic role of ion channel expression in recorded signal instability. We employed siRNA in neuronal culture to find that Kv7.2 knockdown (as a model for the transient downregulation observed at 1 day in vivo) mimics excitatory synaptic remodeling around devices. This work provides new insight into the mechanisms underlying signal loss over time.