High-efficiency grating coupler for an ultralow-loss Si3N4-based platform.

Integrated silicon nitride waveguides of 100 nm height can achieve ultralow propagation losses below 0.1 dB/cm at the 1550 nm wavelength band but lack the scattering strength to form efficient grating couplers. An enhanced grating coupler design based on an amorphous silicon layer on top of silicon nitride is proposed and demonstrated to improve the directionality of the coupler. The fabrication process is optimized for a self-alignment process between the amorphous silicon and silicon nitride layers without increasing waveguide losses. Experimental coupling losses of 5 dB and a 3 dB bandwidth of 75 nm are achieved with both regular and focusing designs.

Ultra-sensitive refractive index sensor using CMOS plasmonic transducers on silicon photonic interferometric platform.

Optical refractive-index sensors exploiting selective co-integration of plasmonics with silicon photonics has emerged as an attractive technology for biosensing applications that can unleash unprecedented performance breakthroughs that reaps the benefits of both technologies. However, towards this direction, a major challenge remains their integration using exclusively CMOS-compatible materials. In this context, herein, we demonstrate, for the first time to our knowledge, a CMOS-compatible plasmo-photonic Mach-Zehnder-interferometer (MZI) based on aluminum and Si3N4 waveguides, exhibiting record-high bulk sensitivity of 4764 nm/RIU with clear potential to scale up the bulk sensitivity values by properly engineering the design parameters of the MZI. The proposed sensor is composed of Si3N4 waveguides butt-coupled with an aluminum stripe in one branch to realize the sensing transducer. The reference arm is built by Si3N4 waveguides, incorporating a thermo-optic phase shifter followed by an MZI-based variable optical attenuation stage to maximize extinction ratio up to 38 dB, hence optimizing the overall sensing performance. The proposed sensor exhibits the highest bulk sensitivity among all plasmo-photonic counterparts, while complying with CMOS manufacturing standards, enabling volume manufacturing.

Morphine and MK-801 administration leads to alternative N-methyl-D-aspartate receptor 1 splicing and associated changes in reward seeking behavior and nociception on an operant orofacial assay.

The NMDA receptor plays a large role in opioid-induced plastic changes in the nervous system. The expression levels of its NR1 subunit are altered dramatically by morphine but no changes in its alternative splicing have been reported. Changes in the splicing of the N1, C1, C2, and C2' cassettes can alter the pharmacology and regulation of this receptor. Western Blots run on brain tissue from rats made tolerant to morphine revealed altered splicing of the N1 cassettes in the accumbens and amygdala (AMY), and the C1 cassette in the AMY and the dorsal hippocampus (HIPP). After 3days of withdrawal C2'-containing NR1 subunits were down-regulated in each of these areas. These were not due to acute doses of morphine and may represent long-term alterations in drug-induced neuroplasticity. We also examined the effects of morphine tolerance on an operant orofacial nociception assay which forces an animal to endure an aversive heat stimulus in order to receive a sweet milk reward. Morphine decreased pain sensitivity as expected but also increased motivational reward seeking in this task. NMDAR antagonism potentiated this reward seeking behavior suggesting that instead of attenuating tolerance, MK-801 may actually alter the rewarding and/or motivational properties of morphine. When combined, MK-801 and morphine had an additive effect which led to altered splicing in the accumbens, AMY, and the HIPP. In conclusion, NR1 splicing may play a major role in the cognitive behavioral aspects especially in motivational reward-seeking behaviors.

Lesioning of TRPV1 expressing primary afferent neurons prevents PAR-2 induced motility, but not mechanical hypersensitivity in the rat colon.

BACKGROUND: Proteinase activated receptor 2 (PAR-2) is expressed by many neurons in the colon, including primary afferent neurons that co-express transient receptor potential vanilloid 1 (TRPV1). Activation of PAR-2 receptors was previously found to enhance colonic motility, increase secretion and produce hypersensitivity to mechanical stimuli. This study examined the functional role of TRPV1/PAR-2 expressing neurons that innervate the colon by lesioning TRPV1 bearing neurons with the highly selective and potent TRPV1 agonist resiniferatoxin. METHODS: Colonic motility in response to PAR-2 activation was evaluated in vitro using isolated segments of descending colon and in vivo using manometry. Colonic mechanical nociceptive thresholds were measured using colorectal distension. Transient receptor potential vanilloid 1 expressing neurons were selectively lesioned with resiniferatoxin. KEY RESULTS: In vitro, the PAR-2 agonists, trypsin and SLIGRL did not alter contractions of colon segments when applied alone, however, the agents enhanced acetylcholine stimulated contraction. In vivo, PAR-2 agonists administered intraluminally induced contractions of the colon and produced hypersensitivity to colorectal distention. The PAR-2 agonist enhancement of colonic contraction was eliminated when TRPV1 expressing neurons were lesioned with resiniferatoxin, but the PAR-2 agonist induced hypersensitivity remained in the lesioned animals. CONCLUSIONS & INFERENCES: Our findings indicate that TRPV1/PAR-2 expressing primary afferent neurons mediate an extrinsic motor reflex pathway in the colon. These data, coupled with our previous studies, also indicate that the recently described colospinal afferent neurons are nociceptive, suggesting that these neurons may be useful targets for the pharmacological control of pain in diseases such as irritable bowel syndrome.

Identification and immunohistochemical characterization of colospinal afferent neurons in the rat.

The classification, morphology and function of enteric neurons have been extensively studied in the small and large intestine. However, little is known about enteric neurons that directly project to the CNS. Previous studies have identified these unique neurons in the rectum, rectospinal neurons, but little was done to characterize them. Therefore, the aim of this study was to identify and characterize enteric neurons in the rat colon that directly project to the CNS by using retrograde neuronal tracing and immunohistochemistry. By applying the retrograde tracers 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) and Fluorogold (FG) to the L6/S1 segments of the spinal cord, we identified these neurons in both the myenteric and submucosal plexuses of the colon. These neurons were immunoreactive for neurofilament (NF) a marker for Adelta-fibers and isolectin-B4 (IB(4)) a marker for C-fibers. These neurons expressed the enzyme neuronal nitric oxide synthase (nNOS) as well as peptides associated with sensory neurons such as substance P (SP) and vasoactive intestinal polypeptide (VIP) but did not express calcitonin gene-related peptide (CGRP). The N-methyl-D-aspartate (NMDA) receptor subunits NR1 and NR2D and proteinase-activated receptor-2 (PAR2) were also found in these neurons. However they did not express the transient receptor potential receptor V1 (TRPV1) or neurokinin 1 receptor (NK1). The expression of the peptides and receptors suggests that there are at least two separate populations of neurons projecting from the colon to the CNS. The data suggest that these colospinal afferent neurons (CANs) might be involved in nociception. Whether sensory information from CANs is perceived by the animal or is part of the parasympathetic reflex is currently not known.

Expression of the N-methyl-D-aspartate receptor NR1 splice variants and NR2 subunit subtypes in the rat colon.

N-methyl-D-aspartate (NMDA) receptors and the expression of their different splice variants and subunits were previously characterized in the brain and spinal cord. However, knowledge on the NMDA receptor expression and function in the enteric nervous system is limited. Previous work suggested that NMDA receptors were involved in a rat model of visceral hypersensitivity. The aim of this study was to characterize the expression of the NMDA receptor NR1 splice variants and the NR2 subunit subtypes in the rat colon. We visualized the expression of NR1 protein in the rat submucosal and myenteric plexuses. The NR1 splice variants found in the colon of rats lacked the N1 and C1 cassettes and contained the C2 and C2' cassettes (NR1(000) and NR1(001)). The NR2B and NR2D subunits were also found in the rat colon. Moreover, NMDA receptors in the rat colon were heteromeric, since NR1 was co-localized with NR2B and NR2D subunits using fluorescent immunohistochemistry. The identification of the NMDA receptors in the enteric nervous system could lead to the development of drugs that selectively modulate bowel function.