Intracellular Ca2+ signals control the development and regeneration of spinal axons downstream of chemical guidance cues, but little is known about the roles of mechanical cues in axon guidance. Here we show that transient receptor potential canonical 1 (TRPC1) subunits assemble mechanosensitive (MS) channels on Xenopus neuronal growth cones that regulate the extension and direction of axon outgrowth on rigid, but not compliant, substrata. Reducing expression of TRPC1 by antisense morpholinos inhibits the effects of MS channel blockers on axon outgrowth and local Ca2+ transients. Ca2+ influx through MS TRPC1 activates the protease calpain, which cleaves the integrin adaptor protein talin to reduce Src-dependent axon outgrowth, likely through altered adhesion turnover. We found that talin accumulates at the tips of dynamic filopodia, which is lost upon cleavage of talin by active calpain. This pathway may also be important in axon guidance decisions since asymmetric inhibition of MS TRPC1 is sufficient to induce growth cone turning. Together our results suggest that Ca2+ influx through MS TRPC1 on filopodia activates calpain to control growth cone turning during development.

Classic in vitro studies have described spike-timing-dependent plasticity (STDP) at a synapse: the connection from neuron A to neuron B is strengthened (or weakened) when A fires before (or after) B within an optimal time window. Accordingly, more recent in vivo works have demonstrated behavioral effects consistent with an STDP mechanism; however, many relied on single-unit recordings. The ability to modify cortical connections becomes useful in the context of injury, when connectivity and associated behavior are compromised. To avoid the need for long-term, stable isolation of single units, one could control timed activation of two cortical sites with paired electrical stimulation. We tested the hypothesis that STDP could be induced via prolonged paired stimulation as quantified by cortical evoked potentials (EPs) in the sensorimotor cortex of awake, behaving monkeys. Paired simulation between two interconnected sites produced robust effects in EPs consistent with STDP, but only at 2/15 tested pairs. The stimulation protocol often produced increases in global network excitability or depression of the conditioned pair. Together, these results suggest that paired stimulation in vivo is a viable method to induce STDP between cortical populations, but that factors beyond activation timing must be considered to produce conditioning effects.

Surface tension driven passive pumping is a microfluidic technology that uses the surface tension present in small droplets to generate flow. To enhance the potential of this type of passive pumping, a new 'micro passive pumping' technique has been developed that allows for high throughput fluidic delivery by combining passive pumping with a small droplet-based fluidic ejection system. Flow rates of up to four milliliters per minute (mL/min) were achieved that are solely limited by the channel geometry and droplet size. Fluid exchange rates can be performed within tens of milliseconds (ms) by delivering fluids from multiple nozzles. The technique can be extended to a multitude of platforms, as channels are not pressurized and therefore do not require bonding to a substrate. This technique provides a novel flow control for high-speed and packeted flow applications without requiring external tubing connections or substrate bonding.

Electrocorticography (ECoG) is an important area of research for Brain-Computer Interface (BCI) development. ECoG, along with some other biopotentials, has spectral characteristics that can be exploited for more optimal front-end performance than is achievable with conventional techniques. This paper optimizes noise performance of such a system and discusses an equalization technique that reduces the analog-to-digital converter (ADC) dynamic range requirements and eliminates the need for a variable gain amplifier (VGA). We demonstrate a fabricated prototype in 1p9m 65 nm CMOS that takes advantage of the presented findings to achieve high-fidelity, full-spectrum ECoG recording. It requires 1.08 μW over a 150 Hz bandwidth for the entire analog front end and only 7 bits of ADC resolution.