Main Menu (Mobile)- Block

Main Menu - Block

custom | custom

Search Results

filters_region_cap | custom

Filter

facetapi-Q2b17qCsTdECvJIqZJgYMaGsr8vANl1n | block

Associated Lab

facetapi-W9JlIB1X0bjs93n1Alu3wHJQTTgDCBGe | block
facetapi-61yz1V0li8B1bixrCWxdAe2aYiEXdhd0 | block
facetapi-PV5lg7xuz68EAY8eakJzrcmwtdGEnxR0 | block
general_search_page-panel_pane_1 | views_panes

2173 Janelia Publications

Showing 131-140 of 2173 results
01/28/22 | PyNeval: A Python Toolbox for Evaluating Neuron Reconstruction Performance.
Zhang H, Liu C, Yu Y, Dai J, Zhao T, Zheng N
Frontiers in Neuroinformatics. 2022 Jan 28;15:767936. doi: 10.3389/fninf.2021.767936

Quality assessment of tree-like structures obtained from a neuron reconstruction algorithm is necessary for evaluating the performance of the algorithm. The lack of user-friendly software for calculating common metrics motivated us to develop a Python toolbox called PyNeval, which is the first open-source toolbox designed to evaluate reconstruction results conveniently as far as we know. The toolbox supports popular metrics in two major categories, geometrical metrics and topological metrics, with an easy way to configure custom parameters for each metric. We tested the toolbox on both synthetic data and real data to show its reliability and robustness. As a demonstration of the toolbox in real applications, we used the toolbox to improve the performance of a tracing algorithm successfully by integrating it into an optimization procedure.

View Publication Page
01/24/22 | Voltage imaging identifies spinal circuits that modulate locomotor adaptation in zebrafish.
Böhm UL, Kimura Y, Kawashima T, Ahrens MB, Higashijima S, Engert F, Cohen AE
Neuron. 2022 Jan 24:. doi: 10.1016/j.neuron.2022.01.001

Motor systems must continuously adapt their output to maintain a desired trajectory. While the spinal circuits underlying rhythmic locomotion are well described, little is known about how the network modulates its output strength. A major challenge has been the difficulty of recording from spinal neurons during behavior. Here, we use voltage imaging to map the membrane potential of large populations of glutamatergic neurons throughout the spinal cord of the larval zebrafish during fictive swimming in a virtual environment. We characterized a previously undescribed subpopulation of tonic-spiking ventral V3 neurons whose spike rate correlated with swimming strength and bout length. Optogenetic activation of V3 neurons led to stronger swimming and longer bouts but did not affect tail beat frequency. Genetic ablation of V3 neurons led to reduced locomotor adaptation. The power of voltage imaging allowed us to identify V3 neurons as a critical driver of locomotor adaptation in zebrafish.

View Publication Page
01/19/22 | Open-source, Python-based, hardware and software for controlling behavioural neuroscience experiments.
Akam T, Lustig A, Rowland JM, Kapanaiah SK, Esteve-Agraz J, Panniello M, Márquez C, Kohl MM, Kätzel D, Costa RM, Walton ME
eLife. 2022 Jan 19;11:. doi: 10.7554/eLife.67846

Laboratory behavioural tasks are an essential research tool. As questions asked of behaviour and brain activity become more sophisticated, the ability to specify and run richly structured tasks becomes more important. An increasing focus on reproducibility also necessitates accurate communication of task logic to other researchers. To these ends, we developed pyControl, a system of open-source hardware and software for controlling behavioural experiments comprising a simple yet flexible Python-based syntax for specifying tasks as extended state machines, hardware modules for building behavioural setups, and a graphical user interface designed for efficiently running high-throughput experiments on many setups in parallel, all with extensive online documentation. These tools make it quicker, easier, and cheaper to implement rich behavioural tasks at scale. As important, pyControl facilitates communication and reproducibility of behavioural experiments through a highly readable task definition syntax and self-documenting features. Here, we outline the system's design and rationale, present validation experiments characterising system performance, and demonstrate example applications in freely moving and head-fixed mouse behaviour.

View Publication Page
01/18/22 | Identifying Inhibitors of -1 Programmed Ribosomal Frameshifting in a Broad Spectrum of Coronaviruses.
Munshi S, Neupane K, Ileperuma SM, Halma MT, Kelly JA, Halpern CF, Dinman JD, Loerch S, Woodside MT
Viruses. 2022 Jan 18;14(2):. doi: 10.3390/v14020177

Recurrent outbreaks of novel zoonotic coronavirus (CoV) diseases in recent years have highlighted the importance of developing therapeutics with broad-spectrum activity against CoVs. Because all CoVs use -1 programmed ribosomal frameshifting (-1 PRF) to control expression of key viral proteins, the frameshift signal in viral mRNA that stimulates -1 PRF provides a promising potential target for such therapeutics. To test the viability of this strategy, we explored whether small-molecule inhibitors of -1 PRF in SARS-CoV-2 also inhibited -1 PRF in a range of bat CoVs-the most likely source of future zoonoses. Six inhibitors identified in new and previous screens against SARS-CoV-2 were evaluated against the frameshift signals from a panel of representative bat CoVs as well as MERS-CoV. Some drugs had strong activity against subsets of these CoV-derived frameshift signals, while having limited to no effect on -1 PRF caused by frameshift signals from other viruses used as negative controls. Notably, the serine protease inhibitor nafamostat suppressed -1 PRF significantly for multiple CoV-derived frameshift signals. These results suggest it is possible to find small-molecule ligands that inhibit -1 PRF specifically in a broad spectrum of CoVs, establishing frameshift signals as a viable target for developing pan-coronaviral therapeutics.

View Publication Page
01/15/22 | Fluorescent chemigenetic actuators and indicators for use in living animals.
Farrants H, Tebo AG
Current Opinion in Pharmacology. 2022 Jan 15;62:159-167. doi: 10.1016/j.coph.2021.12.007

Fluorescent indicators and actuators provide a means to optically observe and perturb dynamic events in living animals. Although chemistry and protein engineering have contributed many useful tools to observe and perturb cells, an emerging strategy is to use chemigenetics: systems in which a small molecule dye interacts with a genetically encoded protein domain. Here we review chemigenetic strategies that have been successfully employed in living animals as photosensitizers for photoablation experiments, fluorescent cell cycle indicators, and fluorescent indicators for studying dynamic biological signals. Although these strategies at times suffer from challenges, e.g. delivery of the small molecule and assembly of the chemigenetic unit in living animals, the advantages of using small molecules with high brightness, low photobleaching, no chromophore maturation time and expanded color palette, combined with the ability to genetically target them to specific cell types, make chemigenetic fluorescent actuators and indicators an attractive strategy for use in living animals.

View Publication Page
01/12/22 | [Dilemma and breakthrough of acupuncture-moxibustion department under the situation of rapid expansion of hospital].
Chen S, Pan W, Jing X, Fang J
Zhongguo Zhen Jiu. 2022 Jan 12;42(1):8-12. doi: 10.13703/j.0255-2930.20201121-0002

Under the situation of the rapid expansion of hospital, the dilemma of acupuncture-moxibustion department, as well as the relevant solutions are explored. The main reasons for the shrinking situation of the service in acupuncture-moxibustion department include: the disease-based department division trends to divert many diseases suitably treated in acupuncture-moxibustion department; the environment pursuing economic benefits restricts the development of acupuncture-moxibustion therapy characterized by "simple and low-cost operation". There are three important approaches for breaking through the dilemma of acupuncture and moxibustion therapy. First, modifying the traditional service mode as waiting for patients in acupuncture-moxibustion department and promoting acupuncture and moxibustion technology to be adopted in other departments rather than limited only in acupuncture-moxibustion department. Second, increasing the charges of acupuncture and moxibustion technology rationally. Third, positioning accurately the role of acupuncture and moxibustion technology in health services based on its own characteristics and advantages and promoting it in community medical institutions. All of these solutions require the guidance of supporting policies.

View Publication Page
01/12/22 | Toroidal topology of population activity in grid cells.
Gardner RJ, Hermansen E, Pachitariu M, Burak Y, Baas NA, Dunn BA, Moser M, Moser EI
Nature. 2022 Jan 12;602(7895):123-128. doi: 10.1038/s41586-021-04268-7

The medial entorhinal cortex is part of a neural system for mapping the position of an individual within a physical environment. Grid cells, a key component of this system, fire in a characteristic hexagonal pattern of locations, and are organized in modules that collectively form a population code for the animal's allocentric position. The invariance of the correlation structure of this population code across environments and behavioural states, independent of specific sensory inputs, has pointed to intrinsic, recurrently connected continuous attractor networks (CANs) as a possible substrate of the grid pattern. However, whether grid cell networks show continuous attractor dynamics, and how they interface with inputs from the environment, has remained unclear owing to the small samples of cells obtained so far. Here, using simultaneous recordings from many hundreds of grid cells and subsequent topological data analysis, we show that the joint activity of grid cells from an individual module resides on a toroidal manifold, as expected in a two-dimensional CAN. Positions on the torus correspond to positions of the moving animal in the environment. Individual cells are preferentially active at singular positions on the torus. Their positions are maintained between environments and from wakefulness to sleep, as predicted by CAN models for grid cells but not by alternative feedforward models. This demonstration of network dynamics on a toroidal manifold provides a population-level visualization of CAN dynamics in grid cells.

View Publication Page
01/10/21 | A neuropeptidergic circuit gates selective escape behavior of Drosophila larvae.
Imambocus BN, Zhou F, Formozov A, Wittich A, Tenedini FM, Hu C, Sauter K, Macarenhas Varela E, Herédia F, Casimiro AP, Macedo A, Schlegel P, Yang C, Miguel-Aliaga I, Wiegert JS, Pankratz MJ, Gontijo AM, Cardona A, Soba P
Current Biology. 2022 Jan 10;32(1):149-63. doi: 10.1016/j.cub.2021.10.069

Animals display selective escape behaviors when faced with environmental threats. Selection of the appropriate response by the underlying neuronal network is key to maximizing chances of survival, yet the underlying network mechanisms are so far not fully understood. Using synapse-level reconstruction of the Drosophila larval network paired with physiological and behavioral readouts, we uncovered a circuit that gates selective escape behavior for noxious light through acute and input-specific neuropeptide action. Sensory neurons required for avoidance of noxious light and escape in response to harsh touch, each converge on discrete domains of neuromodulatory hub neurons. We show that acute release of hub neuron-derived insulin-like peptide 7 (Ilp7) and cognate relaxin family receptor (Lgr4) signaling in downstream neurons are required for noxious light avoidance, but not harsh touch responses. Our work highlights a role for compartmentalized circuit organization and neuropeptide release from regulatory hubs, acting as central circuit elements gating escape responses.

View Publication Page
Sternson Lab
01/07/22 | Characterization of ultrapotent chemogenetic ligands for research applications in non-human primates
Jessica Raper , Mark A. G. Eldridge , Scott. M. Sternson , Jalene Y. Shim , Grace P. Fomani , Barry J. Richmond , Thomas Wichmann , Adriana Galvan
bioRxiv. 2022 Jan 07:. doi: 10.1101/2022.01.06.475241

Chemogenetics is a technique for obtaining selective pharmacological control over a cell population by expressing an engineered receptor that is selectively activated by an exogenously administered ligand. A promising approach for neuronal modulation involves the use of “Pharmacologically Selective Actuator Modules” (PSAMs); these chemogenetic receptors are selectively activated by ultrapotent “Pharmacologically Selective Effector Molecules” (uPSEMs). To extend the use of PSAM/PSEMs to studies in nonhuman primates it is necessary to thoroughly characterize the efficacy and safety of these tools. We describe the time course and brain penetrance in rhesus monkeys of two compounds with promising binding specificity and efficacy profiles in in vitro studies, uPSEM792 and uPSEM817, after systemic administration. Rhesus macaques received subcutaneous (s.c.) or intravenous (i.v.) administration of uPSEM817(0.064 mg/kg) or uPSEM792 (0.87 mg/kg) and plasma and CSF samples were collected over the course of 48 hours. Both compounds exhibited good brain penetrance, relatively slow washout and negligible conversion to potential metabolites - varenicline or hydroxyvarenicline. In addition, we found that neither of these uPSEMs significantly altered heart rate or sleep. Our results indicate that both compounds are suitable candidates for neuroscience studies using PSAMs in nonhuman primates.

View Publication Page
01/05/22 | Rapid synaptic plasticity contributes to a learned conjunctive code of position and choice-related information in the hippocampus.
Zhao X, Hsu C, Spruston N
Neuron. 2022 Jan 05;110(1):96-108.e4. doi: 10.1016/j.neuron.2021.10.003

To successfully perform goal-directed navigation, animals must know where they are and what they are doing-e.g., looking for water, bringing food back to the nest, or escaping from a predator. Hippocampal neurons code for these critical variables conjunctively, but little is known about how this "where/what" code is formed or flexibly routed to other brain regions. To address these questions, we performed intracellular whole-cell recordings in mouse CA1 during a cued, two-choice virtual navigation task. We demonstrate that plateau potentials in CA1 pyramidal neurons rapidly strengthen synaptic inputs carrying conjunctive information about position and choice. Plasticity-induced response fields were modulated by cues only in animals previously trained to collect rewards based on available cues. Thus, we reveal that gradual learning is required for the formation of a conjunctive population code, upstream of CA1, while plateau-potential-induced synaptic plasticity in CA1 enables flexible routing of the code to downstream brain regions.

View Publication Page