Kevin P. Pipe

Intradental neurons encode tooth sensation, yet identifying them without sacrificing tooth structural integrity remains challenging. Here, we present a protocol for the non-invasive electrical stimulation of intradental neurons with single-molar tooth resolution in anesthetized mice. We describe details for head fixation to access molars. We then provide steps to deliver direct current (DC) pulses to an individual molar while simultaneously monitoring induced current. The protocol can be combined with neural imaging to identify and characterize intradental sensory responses and circuits. For complete details on the use and execution of this protocol, please refer to Ronan et al. 1 • Fabricating a custom mouse stereotaxic stage and retractors for molar access • Assembly of an electrical stimulator setup to target individual molars • Procedures for selective intradental neuron activation in anesthetized mice Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. Intradental neurons encode tooth sensation, yet identifying them without sacrificing tooth structural integrity remains challenging. Here, we present a protocol for the non-invasive electrical stimulation of intradental neurons with single-molar tooth resolution in anesthetized mice. We describe details for head fixation to access molars. We then provide steps to deliver direct current (DC) pulses to an individual molar while simultaneously monitoring induced current. The protocol can be combined with neural imaging to identify and characterize intradental sensory responses and circuits.

Using a nondestructive, in situ near-infrared defect imaging technique, we obtained time-resolved images of dark line defect (DLD) growth in the cavities of several high-power 790-nm diode lasers and calculated individual DLD growth rates. A clear longitudinal spatial dependence in the DLD growth rate was observed, in which the DLD growth rate was faster near the anti-reflective (AR) facet. Longitudinal spatial hole burning simulation results indicate that the total photon density increases toward the AR facet, while the carrier density decreases toward the AR facet. These results suggest that photon absorption plays a key role in enhancing DLD growth beyond the contribution of the traditional carrier capture mechanism. Asymmetric DLD growth that was preferentially directed toward the high-reflectivity facet was also observed, providing further support for the role of photon absorption in the growth process. To account for these findings, we propose a photon-accelerated mechanism for the enhancement of DLD growth in which the slower carrier capture process in the traditional recombination-enhanced dislocation glide mechanism is replaced by a faster photon absorption process.

Abstract Selective brain cooling (SBC) is achieved by cooling the carotid artery of rats with an extravascular thermoelectric concentrated cooling probe. The efficacy of this technique is established by directly measuring temperature at the brain, rectal/core, and intrajugular locations. The level of brain cooling achieved is compared against that of a conventional clinical hypothermia intervention, simulated with a cooling blanket placed on the rat's abdomen. With the probe, brain temperature decreased rapidly (4.19 ± 3.15 °C/h) and independently of the core (−0.84 ± 2.59 °C/h) when applying 0 °C. Histological evaluations of the carotid tissue and blood samples showed no adverse pathological changes from the technique. By contrast, systemic hypothermia via cooling blanket showed steep brain cooling (−8.22 ± 3.35 °C/h) at the expense of significant losses in core temperature (−15.31 ± 6.60 °C/h). Localized brain cooling as demonstrated with the probe allows increased controllability and potential for therapeutic use provided it is validated in larger animal models. A sophisticated SBC technique will enable future investigations into decoupling and reducing the detrimental side effects of systemic hypothermia from its benefits.

Perception of external temperature is essential for maintaining homeostasis and avoiding thermal injury. Although molecular thermosensors such as transient receptor potential melastatin type 8 (TRPM8) have been identified, the neural circuits responsible for transmitting cool signals remain unclear. Here we show that a spinal circuit in mice conveys cool signals from the skin to the brain. Excitatory interneurons in the spinal dorsal horn expressing thyrotropin-releasing hormone receptor (Trhr+) act as a central hub for cool sensation. These Trhr+ neurons receive monosynaptic input from TRPM8+ sensory afferents and are selectively activated by innocuous cool stimuli. Ablating Trhr+ interneurons abolishes behavioral responses to cool, but not to warm or cold stimuli. We also identify a population of calcitonin receptor-like receptor-positive (Calcrl+) spinal projection neurons that receive convergent input from both TRPM8+ afferents and Trhr+ interneurons, and transmit cool-specific signals to the lateral parabrachial nucleus (lPBN). Our findings define a feedforward amplification circuit for cool sensation and reveal a modality-specific spinal pathway for thermal processing. The neural circuits that transmit cool signals remain not fully understood. Here, authors identify a spinal circuit in mice that transmits cool sensations from the skin to the brain, revealing a dedicated neural pathway for detecting innocuous cool temperatures.

The trigeminal sensory neurons that innervate the tooth's vital interior—intradental neurons—are expected to drive severe pain, yet their contribution to healthy tooth sensation has not been explored. Here, we uncover a role for myelinated high-threshold mechano-nociceptors (intradental HTMRs) in tooth protection using in vivo Ca 2+ imaging, opto-/chemogenetics, and the AI-driven behavioral analysis tool LabGym. Intradental HTMRs innervate the inner dentin through overlapping receptive fields and respond as the external structures of the tooth are damaged in the absence of either PIEZO2 or Na v 1.8. Whereas chemogenetic activation of intradental HTMRs results in a pain phenotype marked by facial and postural changes, their transient optogenetic activation triggers a rapid, jaw-opening reflex via contraction of the digastric muscle. Our work indicates that intradental HTMRs not only trigger pain but also protect the teeth by initiating a reflexive movement of the jaws when the teeth experience damage during chewing.

An in situ and nondestructive technique is developed to image the formation and evolution of dark line defects in the cavity of a high-power diode laser. The technique uses broadband near infrared emission that originates in the laser's core layers and enables defects to be imaged with high spatial resolution through the substrate. In particular, it enables defect imaging through the substrate of shorter wavelength lasers, even when the substrate is opaque near the lasing wavelength. The evolution of dark line defects during aging is studied in several devices, with correlations established between the observed characteristics of defect growth and changes in device parameters such as optical power, operating wavelength, threshold current, and slope efficiency. Gradual degradation is found to be associated with dark line defects that slowly propagate from dark spots that are present in the device interior in its fresh (unaged) condition, rather than propagating from spots that are formed during aging, suggesting a strategy to screen fresh devices for expected reliability. This defect growth phenomenon is found to be particularly evident in the dark spots near the output facet.

This work presents a comprehensive study of early aging behavior (<500 hr) in ∼800 nm, phosphide-based laser diodes grown by solid-source MBE with different oxygen concentration levels incorporated into the diode epitaxial layers during growth. The data indicate that lasing characteristics prior to aging are degraded by oxygen introduction, but the gradual power degradation rate after the onset of aging is not a strong function of oxygen at these concentration levels. Devices with oxygen concentrations of ∼2.5 × 10<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">15</sup> cm<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−3</sup> showed significantly longer delay before the onset of aging (incubation time) than devices with less than 1 × 10<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">15</sup> cm<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−3</sup> oxygen. Generation-Recombination current and Laser Beam Induced Current measurements indicate that defect densities and aggregation are suppressed at the facets by oxygen, which can explain longer incubation times. Diagnostic data and parametric fits to diode simulation models show that increased cavity optical loss and defect density are primarily responsible for gradual power degradation during aging, rather than changes in nonradiative recombination. Mechanisms are proposed that explain this behavior, based on density functional theory (DFT) simulations and known recombination-enhanced defect generation phenomena.

The impact of oxygen concentrations less than 4×10<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">15</sup> cm<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−3</sup> on device reliability in Phosphorous-based 800 nm laser diodes was examined. Several aging mechanisms were observed, showing modifications to output power and sudden emitter failure probability due to changes in cavity loss and defect density.

Using a high sensitivity infrared camera, we image the optical cavity of an operating high-power diode laser through a window etched in the substrate and observe weak IR emission from the waveguide core region. The IR intensity maps show dark spots in the cavity that subsequently grow into line defects (all oriented in the same direction) as the laser ages. This technique holds promise as a nondestructive, in situ approach to study the formation and evolution of defects in an operating device. We also use CCD-based thermoreflectance to generate high-resolution facet temperature profiles of the same lasers during aging, with the results suggesting that the slow degradation of optical power that occurs prior to laser failure relates more to cavity defect formation than facet defect (hotspot) formation.

We study the facet temperature distribution of a high-power diode laser over its lifetime using a noncontact, high spatial resolution CCD-based thermoreflectance technique. Based on the known correlation between non-radiative defects and heating, thermal maps can provide valuable information regarding the formation and evolution of small point defects that are at or near the facet during aging. In the laser under study in this work we measure the appearance of local hot spots on the facet, including concentrated hot spots that appear just before or just after COD and are correlated with loss of local light emission. The locations of these hot spots do not exhibit morphology changes in high-resolution SEM imaging of the facet, indicating that the related defects are too small to be observable in SEM or are located at some depth under the facet. Prior to COD, we measure a gradual facet temperature increase accompanied by a gradual optical power decrease and gradual facet optical absorption increase, indicating gradual degradation of the laser.

The catecholamine of polydopamine (PDA) is associated with adhesion and self-polymerization. However, 5,6-dihydroxyindole (DHI) of PDA inevitably consumes primary amine groups, which are helpful for the post-modification of PDA-coated surfaces. Furthermore, DHI leads to particle aggregation by causing π–π interaction and cation−π interaction. Here, we used 3,4-dihydroxybenzylamine hydrobromide to achieve DHI-free poly(catecholamine) (PCA) coating by self-polymerization. The DHI-free nature renders a smooth and uniform surface. Moreover, the suppressed indole ring formation preserves the primary amine groups after the DHI-free PCA coating, suggesting an alternative surface amine functionalization strategy to the conventional silane-based coating that is only applicable to hydroxyl-containing surfaces. Surface amine functionality of DHI-free poly(catecholamine) is confirmed by the fluorescence image of the tethered NHS ester-functionalized polydiacetylene liposome by the NHS ester-amine coupling reaction. Furthermore, DHI-free PCA was used to modify the surface properties of graphene to enhance the thermal conductivity of graphene-polymer composites. Graphene nanoplatelets (GnPs) coated with DHI-free PCA formed adequate intermolecular bonding with the poly(acrylic acid) matrix, which reduces interfacial thermal resistance. The resulting graphene-polymer composites achieved a sharp increase in thermal conductivity, reaching 2.9 W/mK at 15 wt % of graphene content, which is 87% larger than the thermal conductivity of control composites with untreated graphene.