Carbon Nanotubes Confer Unique Properties to Neurons

by Warren Grill, senior technical editor

Carbon nanotubes exhibit unique electrical and mechanical properties and are the subject of intense investigations in biomedicine. In the nervous system, nanotubes have been used to construct matrices for tissue culture and scaffolds for regeneration.

For example, previous work has demonstrated that nanotube substrates can impact the differentiation of precursor (stem) cells. Further, due to their high electrical conductivity and tremendous surface area, nanotube coatings improve both the signal to noise ratio of neural recordings and the efficiency of neural stimulation, as compared to conventional metal microelectrodes.

In a recent publication in Nature Nanotechnology, Giada Cellot and colleagues report on the unique effects of carbon nanotube substrates on the excitability of cultured neurons. The study was led by Michele Giugliano from the Ecole Polytechnique Fédérale de Lausanne in Switzerland (now at the University of Antwerp, Belgium) and Laura Ballerini from the University of Trieste in Italy.

Neurons cultured on nanotube substrates exhibited increased activity when part of a synaptically connected network of cultured neurons, and increased excitability when the network was decoupled with synaptic blockers. The increased excitability resulted from an enhancement of a prolonged membrane depolarization coming after bursts of action potentials. The after-depolarization was mediated by neuronal calcium currents, as demonstrated by application of drugs that block neuronal calcium ­channels.

The investigators hypothesized that the larger after-depolarization resulted from enhanced backpropagating action potentials—action potentials propagating from the soma back into the dendrites, opposite to the conventional direction of action potential propagation. Indeed, both electrical circuit modeling and images of the morphology of neuron substrate interactions suggested that the nanotubes provided a “short circuit” between different locations along the neurons, thereby facilitating backpropagation of action potentials, activation of dendritic calcium channels, and enhancement of the after-depolarization.

Control experiments demonstrated that these effects were specific to the nanotube substrates. First, neurons cultured on smooth substrates of indium tin oxide, which had an electrical conductivity similar to the nanotube substrate, but no nanostructure, exhibited excitability properties comparable to control neurons cultured on glass substrates. Second, neuron cultures on RADA16 peptide substrates, which had a nanostructured surface similar to the nanotube substrate, but no electrical conductivity, were also similar to control neurons cultured on glass. These results indicate that the nanotube substrate effects were specific, and apparently required both an appropriate nanostructured surface and appropriate electrical conductivity to alter the electrical properties of the cultured neurons.

“This result is extremely relevant for the emerging field of neuroengineering and neuroprosthetics,” explained author Giugliano. First, these results highlight the importance of considering the nanoscale properties of materials for interfacing with the nervous system. Materials that are identical at the macroscale could evoke very different responses in the nervous system according to their nanoscale features. Second, the results demonstrate the opportunity to pattern differentially the nanostructured properties of neuronal interfaces to alter and perhaps tailor the excitability of neurons to which they are interfaced. This provides a new level of active control for interfacing with the nervous system.