Soowon Shin

Selectivity of Neuromodulatory Projections from the Basal Forebrain and Locus Ceruleus to Primary Sensory Cortices.

Acetylcholine and noradrenaline are major neuromodulators that affect sensory processing in the cortex. Modality-specific sensory information is processed in defined areas of the cortex, but it is unclear whether cholinergic neurons in the basal forebrain (BF) and noradrenergic neurons in the locus ceruleus (LC) project to and modulate these areas in a sensory modality-selective manner. Here, we mapped BF and LC projections to different sensory cortices of the mouse using dual retrograde tracing. We found that while the innervation of cholinergic neurons into sensory cortices is predominantly modality specific, the projections of noradrenergic neurons diverge onto multiple sensory cortices. Consistent with this anatomy, optogenetic activation of cholinergic neurons in BF subnuclei induces modality-selective desynchronization in specific sensory cortices, whereas activation of noradrenergic LC neurons induces broad desynchronization throughout multiple sensory cortices. Thus, we demonstrate a clear distinction in the organization and function of cholinergic BF and noradrenergic LC projections into primary sensory cortices: cholinergic BF neurons are highly selective in their projections and modulation of specific sensory cortices, whereas noradrenergic LC neurons broadly innervate and modulate multiple sensory cortices. SIGNIFICANCE STATEMENT Neuromodulatory inputs from the basal forebrain (BF) and locus ceruleus (LC) are widespread in the mammalian cerebral cortex and are known to play important roles in attention and arousal, but little is known about the selectivity of their cortical projections. Using a dual retrobead tracing technique along with optogenetic stimulation, we have identified anatomic and functional differences in the way cholinergic BF neurons and noradrenergic LC neurons project into primary sensory cortices. While BF projections are highly selective to individual sensory cortices, LC projections diverge into multiple sensory cortices. To our knowledge, this is the first definitive proof that BF and LC projections to primary sensory cortices show both anatomic and functional differences in selectivity for modulating cortical activity.

Advancements in fabrication process of microelectrode array for a retinal prosthesis using Liquid Crystal Polymer (LCP)

Liquid Crystal Polymer (LCP) has been considered as an alternative biomaterial for implantable biomedical devices primarily for its low moisture absorption rate compared with conventional polymers such as polyimide, parylene and silicone elastomers. A novel retinal prosthetic device based on monolithic encapsulation of LCP is being developed in which entire neural stimulation circuitries are integrated into a thin and eye-conformable structure. Micromachining techniques for fabrication of a LCP retinal electrode array have been previously reported. In this research, however, for being used as a part of the LCP-based retinal implant, we developed advanced fabrication process of LCP retinal electrode through new approaches such as electroplating and laser-machining in order to achieve higher mechanical robustness, long-term reliability and flexibility. Thickened metal tracks could contribute to higher mechanical strength as well as higher long-term reliability when combined with laser-ablation process by allowing high-pressure lamination. Laser-thinning technique could improve the flexibility of LCP electrode.

Novel four-sided neural probe fabricated by a thermal lamination process of polymer films.

BACKGROUND Ideally, neural probes should have channels with a three-dimensional (3-D) configuration to record the activities of 3-D neural circuits. Many types of 3-D neural probes have been developed; however, most of them were designed as an array of multiple shanks with electrodes located along one side of the shanks. NEW METHOD We developed a novel liquid crystal polymer (LCP)-based neural probe with four-sided electrodes. This probe has electrodes on four sides of the shank, i.e., the front, back and two sidewalls. To generate the proposed configuration of the electrodes, we used a thermal lamination process involving LCP films and laser micromachining. RESULTS The proposed novel four-sided neural probe, was used to successfully perform in vivo multichannel neural recording in the mouse primary somatosensory cortex. COMPARISON WITH EXISTING METHOD The multichannel neural recording showed that the proposed four-sided neural probe can record spiking activities from a more diverse neuronal population than single-sided probes. This was confirmed by a pairwise Pearson correlation coefficient (Pearsons r) analysis and a cross-correlation analysis. CONCLUSION The developed four-sided neural probe can be used to record various signals from a complex neural network.

Implantable electrical stimulation bioreactor with liquid crystal polymer based electrodes for enhanced bone regeneration at mandibular large defects in rabbit

The osseous regeneration of large bone defects is still a major clinical challenge in maxillofacial and orthopedic surgery. Our previous studies demonstrated that electrical stimulation (ES) with biphasic current pulse showed proliferative effects on bone cells and enhanced secretion of bone-forming growth factors. This study presents an implantable electrical stimulation bioreactor with electrodes based on liquid crystal polymer (LCP), which has excellent bone-binding property. The bioreactor was implanted into a critical sized bone defect and subjected to ES for one week, where bone regeneration was evaluated four weeks after surgery using micro-CT. The effect of ES via bioreactor was compared with a sham control group and positive control group that received recombinant human bone morphogenetic protein (rhBMP)-2 (20 μg). New bone volume per tissue volume (BV/TV) in the ES and rhBMP-2 groups increased to 171% (p < 0.001) and 210% (p < 0.001), respectively, compared to that in the sham control group. In the histological evaluation, there was no inflammation within bone defects and adjacent to LCP in all groups. This study showed that the ES bioreactor with LCP electrodes could enhance bone regeneration at large bone defects, where LCP can act as a mechanically resistant outer box without inflammation.