Head direction cell activity in mice: Robust directional signal depends on intact otolith organs

The head direction (HD) cell signal is a representation of an animal\u27s perceived directional heading with respect to its environment. This signal appears to originate in the vestibular system, which includes the semicircular canals and otolith organs. Preliminary studies indicate the semicircular canals provide a necessary component of the HD signal, but involvement of otolithic information in the HD signal has not been tested. The present study was designed to determine the otolithic contribution to the HD signal, as well as to compare HD cell activity of mice with that of rats. HD cell activity in the anterodorsal thalamus was assessed in wild-type C57BL/6J and otoconia-deficient tilted mice during locomotion within a cylinder containing a prominent visual landmark. HD cell firing properties in C57BL/6J mice were generally similar to those in rats. However, in C57BL/6J mice, landmark rotation failed to demonstrate dominant control of the HD signal in 36% of the sessions. In darkness, directional firing became unstable during 42% of the sessions, but landmark control was not associated with HD signal stability in darkness. HD cells were identified in tilted mice, but directional firing properties were not as robust as those of C57BL/6J mice. Most HD cells in tilted mice were controlled by landmark rotation but showed substantial signal degradation across trials. These results support current models that suggest otolithic information is involved in the perception of directional heading. Furthermore, compared with rats, the HD signal in mice appears to be less reliably anchored to prominent environmental cues. Copyright © 2009 Society for Neuroscience

Is navigation in virtual reality with fMRI really navigation?

Identifying the neural mechanisms underlying spatial orientation and navigation has long posed a challenge for researchers. Multiple approaches incorporating a variety of techniques and animal models have been used to address this issue. More recently, virtual navigation has become a popular tool for understanding navigational processes. Although combining this technique with functional imaging can provide important information on many aspects of spatial navigation, it is important to recognize some of the limitations these techniques have for gaining a complete understanding of the neural mechanisms of navigation. Foremost among these is that, when participants perform a virtual navigation task in a scanner, they are lying motionless in a supine position while viewing a video monitor. Here, we provide evidence that spatial orientation and navigation rely to a large extent on locomotion and its accompanying activation of motor, vestibular, and proprioceptive systems. Researchers should therefore consider the impact on the absence of these motion-based systems when interpreting virtual navigation/functional imaging experiments to achieve a more accurate understanding of the mechanisms underlying navigation. © 2013 Massachusetts Institute of Technology

Visual landmark information gains control of the head direction signal at the lateral mammillary nuclei

The neural representation of directional heading is conveyed by head direction (HD) cells located in an ascending circuit that includes projections from the lateral mammillary nuclei (LMN) to the anterodorsal thalamus (ADN) to the postsubiculum (PoS). The PoS provides return projections to LMN and ADN and is responsible for the landmark control of HD cells in ADN. However, the functional role of the PoS projection to LMN has not been tested. The present study recorded HD cells from LMN after bilateral PoS lesions to determine whether the PoS provides landmark control toLMNHDcells. After the lesion and implantation of electrodes,HDcell activity was recorded while rats navigated within a cylindrical arena containing a single visual landmark or while they navigated between familiar and novel arenas of a dual-chamber apparatus. PoS lesions disrupted the landmark control of HD cells and also disrupted the stability of the preferred firing direction of the cells in darkness. Furthermore, PoS lesions impaired the stable HD cell representation maintained by path integration mechanisms when the rat walked between familiar and novel arenas. These results suggest that visual information first gains control of the HD cell signal in the LMN, presumably via the direct PoS→LMN projection. This visual landmark information then controls HD cells throughout the HD cell circuit. ©2015 the authors

Motion Robust Magnetic Susceptibility and Field Inhomogeneity Estimation Using Regularized Image Restoration Techniques for fMRI

In functional MRI, head motion may cause dynamic nonlinear field-inhomogeneity changes, especially with large out-of-plane rotations. This may lead to dynamic geometric distortion or blurring in the time series, which may reduce activation detection accuracy. The use of image registration to estimate dynamic field inhomogeneity maps from a static field map is not sufficient in the presence of such rotations. This paper introduces a retrospective approach to estimate magnetic susceptibility induced field maps of an object in motion, given a static susceptibility induced field map and the associated object motion parameters. It estimates a susceptibility map from a static field map using regularized image restoration techniques, and applies rigid body motion to the former. The dynamic field map is then computed using susceptibility voxel convolution. The method addresses field map changes due to out-of-plane rotations during time series acquisition and does not involve real time field map acquisitions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85944/1/Fessler233.pd

Identification of clonal hematopoiesis mutations in solid tumor patients undergoing unpaired next-generation sequencing assays

Purpose: In this era of precision-based medicine, for optimal patient care, results reported from commercial next-generation sequencing (NGS) assays should adequately reflect the burden of somatic mutations in the tumor being sequenced. Here, we sought to determine the prevalence of clonal hematopoiesis leading to possible misattribution of tumor mutation calls on unpaired Foundation Medicine NGS assays. Experimental Design: This was a retrospective cohort study of individuals undergoing NGS of solid tumors from two large cancer centers. We identified and quantified mutations in genes known to be frequently altered in clonal hematopoiesis (DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2, SF3B1, CBL, JAK2) that were returned to physicians on clinical Foundation Medicine reports. For a subset of patients, we explored the frequency of true clonal hematopoiesis by comparing mutations on Foundation Medicine reports with matched blood sequencing. Results: Mutations in genes that are frequently altered in clonal hematopoiesis were identified in 65% (1,139/1,757) of patients undergoing NGS. When excluding TP53, which is often mutated in solid tumors, these events were still seen in 35% (619/1,757) of patients. Utilizing paired blood specimens, we were able to confirm that 8% (18/226) of mutations reported in these genes were true clonal hematopoiesis events. The majority of DNMT3A mutations (64%, 7/11) and minority of TP53 mutations (4%, 2/50) were clonal hematopoiesis. Conclusions: Clonal hematopoiesis mutations are commonly reported on unpaired NGS testing. It is important to recognize clonal hematopoiesis as a possible cause of misattribution of mutation origin when applying NGS findings to a patient's care

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

A Diagram of the Social-Ecological Conditions of Opioid Misuse and Overdose

The United States is experiencing a crisis of opioid misuse and overdose. To understand the underlying factors, researchers have begun looking upstream to identify social and structural determinants. However, no study has yet aggregated these into a comprehensive ecology of opioid overdose. We scoped 68 literature sources and compiled a master list of opioid misuse and overdose conditions. We grouped the conditions and used the Social Ecological Model to organize them into a diagram. We reviewed the diagram with nine subject matter experts (SMEs) who provided feedback on its content, design, and usefulness. From a literature search and SME interviews, we identified 80 unique conditions of opioid overdose and grouped them into 16 categories. In the final diagram, we incorporated 40 SME-recommended changes. In commenting on the diagram’s usefulness, SMEs explained that the diagram could improve intervention planning by demonstrating the complexity of opioid overdose and highlighting structural factors. However, care is required to strike a balance between comprehensiveness and legibility. Multiple design formats may be useful, depending on the communication purpose and audience. This ecological diagram offers a visual perspective of the conditions of opioid overdose. © 2023 by the authors.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]