SUMMARY
The prevailing view is that striatal parvalbumin (PV)-positive interneurons primarily function to downregulate medium spiny projection neuron (MSN) activity via monosynaptic inhibitory signaling. Here, by combining in vivo neural recordings and optogenetics, we unexpectedly find that both suppressing and over-activating PV cells attenuates spontaneous MSN activity. To account for this, we find that in addition to monosynaptic coupling, PV-MSN interactions are mediated by a competing disynaptic inhibitory circuit involving a variety of neuropeptide Y-expressing interneurons. Next we use optogenetic and chemogenetic approaches to show that dorsolateral striatal PV interneurons influence the initial expression of reward-conditioned responses, but that their contribution to performance declines with experience. Consistent with this, we observe with large-scale recordings in behaving animals that the relative contribution of PV cells on MSN activity diminishes with training. Together, this work provides a possible mechanism by which PV interneurons modulate striatal output and selectively enhance performance early in learning.
Simultaneous localization and mapping problem for mobile robots has received considerable attention over the last decade. The widely used formulation of the SLAM problem has been the augmented state approach in an estimation theoretic framework. Although, many related issues of SLAM such as computational complexity, loop closing and data association have received much attention, the observability issue has largely remained ignored. System observability is an important aspect in any state estimation problem. Observability analysis provides for understanding of the fundamental limits of the solution obtainable, regardless of process and measurement noises. The standard world-centric SLAM formulation is a highly non-linear system. Thus the direct use of linear observability tools and criteria in the analysis of its observability yields incorrect and inconsistent results. In this paper an appropriate method of analysis of the observability of non-linear systems is applied to investigate the properties of the standard SLAM formulation. Contrary to popular belief, it is shown through theoretical analysis that the standard 2D planar world-centric SLAM formulation involving odometry inputs for robot speed and heading, and range/bearing measurements to features in the environment is unobservable. It is also shown that for the system to be observable, it requires at least two absolutely known feature point positions, thus questioning the very meaning implied by SLAM. The analytical results thus established are verified through simulations.
The healthcare system relies widely on biochemical information obtained from blood sample extracted via hypodermic needles, despite the invasiveness and pain associated with this procedure. Therefore, an alternative micro-scale needle for minimally invasive blood sampling is highly desirable. Traditional fabrication techniques to create microneedles do not generate needles with the combined features of a sharp tip, long length, and hollow structure concurrently. Here, we report the fabrication of a microneedle long enough to reach blood vessels and sharp enough to minimize nerve contact for minimally invasive blood extraction. The microneedle structure was precisely controlled using a drawing lithography technique, and a sharp tip angle was introduced using a laser-cutting system. We investigated the characteristics of a microneedle with a length of 1,800 μm length, an inner diameter of 60 μm, a tip diameter of 120 μm, and a 15° bevel angle through in-vitro liquid extraction and mechanical strength analysis. We demonstrated that the proposed structure results in blood extraction at a reasonable rate, and that a microneedle with this geometry can reliably penetrate skin without breaking. We integrated this microneedle into a blood extraction device to extract a 20 μl volume of mouse blood in-vivo. Our optimized, hollow microneedle can potentially be incorporated with other cutting-edge technologies such as microactuators, biosensors, and microfluidic chips to create blood analysis systems for point-of-care diagnostics.
Inflammatory cytokines (IL-6, TNF-α, PGE2, and NO) seem to play a crucial role in hypertrophy and ossification of LF. Degenerated, herniated intervertebral disks, and facet arthrosis may influence LF through inflammatory cytokines and cause hypertrophy and ossification of LF.
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