Optical phased array neural probes for beam-steering in brain tissue.

Implantable silicon neural probes with integrated nanophotonic waveguides can deliver patterned dynamic illumination into brain tissue at depth. Here, we introduce neural probes with integrated optical phased arrays and demonstrate optical beam steering in vitro. Beam formation in brain tissue is simulated and characterized. The probes are used for optogenetic stimulation and calcium imaging.

Optogenetic manipulation of medullary neurons in the locust optic lobe.

The locust is a widely used animal model for studying sensory processing and its relation to behavior. Due to the lack of genomic information, genetic tools to manipulate neural circuits in locusts are not yet available. We examined whether Semliki Forest virus is suitable to mediate exogenous gene expression in neurons of the locust optic lobe. We subcloned a channelrhodopsin variant and the yellow fluorescent protein Venus into a Semliki Forest virus vector and injected the virus into the optic lobe of locusts ( Schistocerca americana). Fluorescence was observed in all injected optic lobes. Most neurons that expressed the recombinant proteins were located in the first two neuropils of the optic lobe, the lamina and medulla. Extracellular recordings demonstrated that laser illumination increased the firing rate of medullary neurons expressing channelrhodopsin. The optogenetic activation of the medullary neurons also triggered excitatory postsynaptic potentials and firing of a postsynaptic, looming-sensitive neuron, the lobula giant movement detector. These results indicate that Semliki Forest virus is efficient at mediating transient exogenous gene expression and provides a tool to manipulate neural circuits in the locust nervous system and likely other insects. NEW & NOTEWORTHY Using Semliki Forest virus, we efficiently delivered channelrhodopsin into neurons of the locust optic lobe. We demonstrate that laser illumination increases the firing of the medullary neurons expressing channelrhodopsin and elicits excitatory postsynaptic potentials and spiking in an identified postsynaptic target neuron, the lobula giant movement detector neuron. This technique allows the manipulation of neuronal activity in locust neural circuits using optogenetics.

[THE ROLE OF SIMULATION IN SURGICAL TRAINING--A NEW ERA].

Surgical training, which was traditionally based on the apprentice model, is undergoing a fundamental change since the introduction of virtual reality simulators into the training program of surgical residents. With the introduction of these simulators we can expect to see an improvement in the surgical abilities of new surgeons and a decrease in costs--as seen in the aviation world. Virtual reality simulators include a visual and tactile interface which is meant to train young surgeons in full procedure before the actual surgery. The available operation encompasses a multitude of surgical disciplines--gynecology, urology, orthopedics, vascular surgery, general surgery and more. The simulator allows the surgeon to practice complicated procedures and to be exposed to emergency situations without risking the patient's life. We opened in the Carmel Medical Center a multi disciplinary simulation center 18 months ago. The center includes simulators for gynecology, orthopedics, urology, general surgery, vascular surgery and advanced cardiac life support. The center cooperates with the Faculty of Medicine at the Technion in order to train young surgeons in all surgical disciplines. In this period of time we followed the improvement in the endoscopic abilities of the basic skills course participants.

Displacement detection with a vibrating rf superconducting interference device: beating the standard linear limit.

We study a configuration for displacement detection consisting of a nanomechanical resonator coupled to both a radio frequency superconducting interference device and to a superconducting stripline resonator. We employ an adiabatic approximation and rotating wave approximation and calculate the displacement sensitivity. We study the performance of such a displacement detector when the stripline resonator is driven into a region of nonlinear oscillations. In this region the system exhibits noise squeezing in the output signal when homodyne detection is employed for readout. We show that displacement sensitivity of the device in this region may exceed the upper bound imposed upon the sensitivity when operating in the linear region. On the other hand, we find that the high displacement sensitivity is accompanied by a slowing down of the response of the system, resulting in a limited bandwidth.

Patterned photostimulation via visible-wavelength photonic probes for deep brain optogenetics.

Optogenetic methods developed over the past decade enable unprecedented optical activation and silencing of specific neuronal cell types. However, light scattering in neural tissue precludes illuminating areas deep within the brain via free-space optics; this has impeded employing optogenetics universally. Here, we report an approach surmounting this significant limitation. We realize implantable, ultranarrow, silicon-based photonic probes enabling the delivery of complex illumination patterns deep within brain tissue. Our approach combines methods from integrated nanophotonics and microelectromechanical systems, to yield photonic probes that are robust, scalable, and readily producible en masse. Their minute cross sections minimize tissue displacement upon probe implantation. We functionally validate one probe design in vivo with mice expressing channelrhodopsin-2. Highly local optogenetic neural activation is demonstrated by recording the induced response-both by extracellular electrical recordings in the hippocampus and by two-photon functional imaging in the cortex of mice coexpressing GCaMP6.

The effect of bladder fullness on evaluation of pelvic organ prolapse.

OBJECTIVE: To investigate the effect of bladder fullness on pelvic organ prolapse (POP) staging via the Pelvic Organ Prolapse Quantification System (POP-Q). METHODS: Sixty women with advanced POP underwent pelvic examination with maximal Valsalva straining via POP-Q with an empty bladder and after transcatheter bladder filling to maximum cystometric capacity, with simultaneous intra-abdominal and intravesical pressure recordings. Main outcome measures included POP-Q values and staging with full versus empty bladder. RESULTS: An empty bladder was associated with a significantly higher POP-Q staging (median, 3 vs 2; P<0.0001); and a lower location of points Ba (4.51 vs 1.37; P<0.0001), Aa (2.58 vs 0.62; P<0.0001), Bp (-0.68 vs -1.10; P=0.01), Ap (0.83 vs -1.27; P=0.002), C (1.57 vs -1.07; P<0.0001), and D (0.14 vs -2.77; P<0.0001) compared with a full bladder. However, genital hiatus, perineal body, and total vaginal length values were not significantly affected by bladder fullness. No differences in intra-abdominal or detrusor pressures were noted between empty and full bladder states. CONCLUSION: POP-Q assessment with a full bladder is associated with underestimation of POP severity. Therefore, bladder emptying should be a standard requirement for POP-Q staging and reporting.

Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner.

We investigated the role of Lef1, one of the four transcription factors that transmit Wnt signaling to the genome, in the regulation of bone mass. Microcomputed tomographic analysis of 13- and 17-week-old mice revealed significantly reduced trabecular bone mass in Lef1(+/-) females compared to littermate wild-type females. This was attributable to decreased osteoblast activity and bone formation as indicated by histomorphometric analysis of bone remodeling. In contrast to females, bone mass was unaffected by Lef1 haploinsufficiency in males. Similarly, females were substantially more responsive than males to haploinsufficiency in Gsk3beta, a negative regulator of the Wnt pathway, displaying in this case a high bone mass phenotype. Lef1 haploinsufficiency also led to low bone mass in males lacking functional androgen receptor (AR) (tfm mutants). The protective skeletal effect of AR against Wnt-related low bone mass is not necessarily a result of direct interaction between the AR and Wnt signaling pathways, because Lef1(+/-) female mice had normal bone mass at the age of 34 weeks. Thus, our results indicate an age- and gender-dependent role for Lef1 in regulating bone formation and bone mass in vivo. The resistance to Lef1 haploinsufficiency in males with active AR and in old females could be due to the reduced bone turnover in these mice.