August 20, 2010 |
by Warren Grill, senior technical editor
August 20, 2010
Nanotechnology is permeating fields as diverse as fabric coatings and telecommunications, and neurotechnology is no different. Last year we reported on the use of carbon nanotubes as a substrate for cultured neurons [NBR Mar09 p1]. Remarkably, neurons cultured on the carbon nanotube substrates exhibited greater excitability as a result of an electrical short circuit along the neurons produced by the highly conductive nanotubes. Now, semiconductor nanowires have been used to increase dramatically the spatial and temporal fidelity of in vitro neural recordings.
Conventional arrays of planar metal microelectrodes typically yield one or fewer neurons per recording contact and it is challenging to isolate recordings from single neurons. This limitation was overcome through the use of arrays of transistors, fabricated from silicon nanowires. Working with Venkatesh Murthy and Charles Lieber at Harvard University, Qing and colleagues positioned neurons on top of the transistor gates, and changes in the gate voltage, produced by neuronal activity, changed the conductance of the transistor. Their results, published in the Proceedings of the National Academy of Sciences, demonstrate recordings from neurons with spatial and temporal fidelity rivaling that of conventional glass patch electrodes.
Brain slices from the olfactory bulb were maintained in vitro on top of the nanowire transistor arrays, and initial recordings were made from olfactory pyramidal cells following electrical stimulation of the lateral olfactory tract. Simultaneous recordings using conventional patch clamp techniques and the nanowires, albeit from different but similarly connected neurons, demonstrated that the nanowire devices enabled high fidelity recording of both presynaptic and post-synaptic potentials.
This assertion was validated by pharmacological experiments. CNQX and APV were used to block AMPA- and NMDA-receptor mediated glutamatergic synaptic transmission, respectively, and enabled isolation of the presynaptic and postsynaptic components of the response. Further, the abolition of all responses following application of the sodium channel blocker tetrodotoxin, demonstrated the neuronal origin of the responses as distinct from the stimulation artifact.
The exceedingly small scale (gate areas of 0.06 square microns) and close spacing (as little as 3 µm between devices) of the nanowire transistors enabled neural recordings with subcellular spatial fidelity. Dendritic and somatic activity each produced unique signatures on spatially isolated devices, and resolution was estimated to be on the order or 5 microns. Further, use of serial devices enabled recording of action potential propagation along axons of the lateral olfactory tract with sub-millisecond resolution. Thus, in contrast to the superposition of signals detected by relatively large metal microelectrodes in conventional planar multi-electrode arrays, the nanowire devices enabled highly selective recordings from individual neural elements.
The high temporal and spatial fidelity of nanowire transistors, combined with the ability to detect element specific neural activity, should expand the utility of multi-electrode arrays. High fidelity in vitro recording from brain slices or cultured neurons will find applications in study of connectivity and circuit function as well as drug discovery and testing. This represents a more near term opportunity for nanowires, in contrast to the longer-term opportunities for in vivo applications of nanowires for neural recording or stimulation [NBR Oct05 p1].
