Beyond a Transmission Cable-New Technologies to Reveal the Richness in Axonal Electrophysiology

Abstract

The axon is a neuronal structure capable of processing, encoding, and transmitting information. This assessment contrasts with a limiting, but deeply rooted, perspective where the axon functions solely as a transmission cable of somatodendritic activity, sending signals in the form of stereotypical action potentials. This perspective arose, at least partially, because of the technical difficulties in probing axons: their extreme length-to-diameter ratio and intricate growth paths preclude the study of their dynamics through traditional techniques. Recent findings are challenging this view and revealing a much larger repertoire of axonal computations. Axons display complex signaling processes and structure-function relationships, which can be modulated via diverse activity-dependent mechanisms. Additionally, axons can exhibit patterns of activity that are dramatically different from those of their corresponding soma. Not surprisingly, many of these recent discoveries have been driven by novel technology developments, which allow for in vitro axon electrophysiology with unprecedented spatiotemporal resolution and signal-to-noise ratio. In this review, we outline the state-of-the-art in vitro toolset for axonal electrophysiology and summarize the recent discoveries in axon function it has enabled. We also review the increasing repertoire of microtechnologies for controlling axon guidance which, in combination with the available cutting-edge electrophysiology and imaging approaches, have the potential for more controlled and high-throughput in vitro studies. We anticipate that a larger adoption of these new technologies by the neuroscience community will drive a new era of experimental opportunities in the study of axon physiology and consequently, neuronal function.

Keywords: axon computations; axon electrophysiology; axon guidance; functional imaging; microelectrode arrays.

Figure 1.

Methods for probing axonal activity. Schematic representation of the main experimental approaches to probe axonal activity and the respective stimulation and/or recording capabilities. The labels are merely illustrative and may not represent the signals/waveforms characteristic of each technique.

Figure 2.

Methods for controlling axon guidance. Schematic representations of approaches to control axon guidance via physical (top) and chemical (bottom) patterning. Detailed explanations of each method can be found in the respective subsection [engineered substrates; microfluidics; microcontact printing (µCP); in situ techniques]. For each method, the nature of the guiding feature (continuous; discontinuous, or custom) and possible direction for axon growth (unidirectional; bidirectional; multidirectional, or custom) are described.