Genetic elimination of GABAergic neurotransmission reveals two distinct pacemakers for spontaneous waves of activity in the developing mouse cortex.

Many structures of the mammalian CNS generate propagating waves of electrical activity early in development. These waves are essential to CNS development, mediating a variety of developmental processes, such as axonal outgrowth and pathfinding, synaptogenesis, and the maturation of ion channel and receptor properties. In the mouse cerebral cortex, waves of activity occur between embryonic day 18 and postnatal day 8 and originate in pacemaker circuits in the septal nucleus and the piriform cortex. Here we show that genetic knock-out of the major synthetic enzyme for GABA, GAD67, selectively eliminates the picrotoxin-sensitive fraction of these waves. The waves that remain in the GAD67 knock-out have a much higher probability of propagating into the dorsal neocortex, as do the picrotoxin-resistant fraction of waves in controls. Field potential recordings at the point of wave initiation reveal different electrical signatures for GABAergic and glutamatergic waves. These data indicate that: (1) there are separate GABAergic and glutamatergic pacemaker circuits within the piriform cortex, each of which can initiate waves of activity; (2) the glutamatergic pacemaker initiates waves that preferentially propagate into the neocortex; and (3) the initial appearance of the glutamatergic pacemaker does not require preceding GABAergic waves. In the absence of GAD67, the electrical activity underlying glutamatergic waves shows greatly increased tendency to burst, indicating that GABAergic inputs inhibit the glutamatergic pacemaker, even at stages when GABAergic pacemaker circuitry can itself initiate waves.

A microfluidic D-subminiature connector.

Standardized, affordable, user-friendly world-to-chip interfaces represent one of the major barriers to the adoption of microfluidics. We present a connector system for plug-and-play interfacing of microfluidic devices to multiple input and output lines. The male connectors are based on existing standardized housings from electronics that are inexpensive and widely available. The female connectors are fabricated using familiar replica molding techniques that can easily be adopted by microfluidic developers.

A microfluidic microelectrode array for simultaneous electrophysiology, chemical stimulation, and imaging of brain slices.

In order to understand information processing in neural circuits, it is necessary to detect both electrical and chemical signaling with high spatial and temporal resolution. Although the primary currency of neural information processing is electrical, many of the downstream effects of the electrical signals on the circuits that generate them are dependent on activity-dependent increases in intracellular calcium concentration. It is therefore of great utility to be able to record electrical signals in neural circuits at multiple sites, while at the same time detecting optical signals from reporters of intracellular calcium levels. We describe here a microfluidic multi-electrode array (MMEA) capable of high-resolution extracellular recording from brain slices that is optically compatible with calcium imaging at single cell resolution. We show the application of the MMEA device to record waves of spontaneous activity in developing cortical slices and to perform multi-site extracellular recordings during simultaneous calcium imaging of activity. The MMEA has the unique capability to simultaneously allow focal electrical and chemical stimuli at different locations of the surface of a brain slice.

Device considerations for development of conductance-based biosensors.

Design and fabrication of electronic biosensors based on field-effect-transistor (FET) devices require understanding of interactions between semiconductor surfaces and organic biomolecules. From this perspective, we review practical considerations for electronic biosensors with emphasis on molecular passivation effects on FET device characteristics upon immobilization of organic molecules and an electrostatic model for FET-based biosensors.

Probing molecules in integrated silicon-molecule-metal junctions by inelastic tunneling spectroscopy.

Molecular electronics has drawn significant attention for nanoelectronic and sensing applications. A hybrid technology where molecular devices are integrated with traditional semiconductor microelectronics is a particularly promising approach for these applications. Key challenges in this area include developing devices in which the molecular integrity is preserved, developing in situ characterization techniques to probe the molecules within the completed devices, and determining the physical processes that influence carrier transport. In this study, we present the first experimental report of inelastic electron tunneling spectroscopy of integrated metal-molecule-silicon devices with molecules assembled directly to silicon contacts. The results provide direct experimental confirmation that the chemical integrity of the monolayer is preserved and that the molecules play a direct role in electronic conduction through the devices. Spectra obtained under varying measurement conditions show differences related to the silicon electrode, which can provide valuable information about the physics influencing carrier transport in these molecule/Si hybrid devices.

Lithography-free in situ Pd contacts to templated single-walled carbon nanotubes.

We report a metalization technique for electrically addressing templated vertical single-walled carbon nanotubes (SWNTs) using in situ palladium (Pd) nanowires. SWNTs are synthesized from an embedded catalyst in a modified porous anodic alumina (PAA) template. Pd is electrodeposited into the template to form nanowires that grow from an underlying conductive layer beneath the PAA and extend to the initiation sites of the SWNTs within each pore. In this way, individual vertical channels of SWNTs are created, each with a vertical Pd nanowire back contact. Further Pd deposition results in annular Pd nanoclusters that form on portions of SWNTs extending onto the PAA surface. Two-terminal electrical characteristics produce linear I-V relationships, indicating ohmic contact in the devices.