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1. A modular architecture for organizing, processing and sharing neurophysiology data

Author

Bonacchi, Niccolò, Chapuis, Gaelle A, Churchland, Anne K, DeWitt, Eric EJ, Faulkner, Mayo, Harris, Kenneth D, Huntenburg, Julia M, Hunter, Max, Laranjeira, Inês C, Rossant, Cyrille, Sasaki, Maho, Schartner, Michael M, Shen, Shan, Steinmetz, Nicholas A, Walker, Edgar Y, West, Steven J, Winter, Olivier, and Wells, Miles J

Subjects
Biological Sciences, Behavioral and Social Science, Basic Behavioral and Social Science, Neurophysiology, Databases, Factual, Laboratories, International Brain Laboratory, Technology, Medical and Health Sciences, Developmental Biology, Biological sciences
Abstract

We describe an architecture for organizing, integrating and sharing neurophysiology data within a single laboratory or across a group of collaborators. It comprises a database linking data files to metadata and electronic laboratory notes; a module collecting data from multiple laboratories into one location; a protocol for searching and sharing data and a module for automatic analyses that populates a website. These modules can be used together or individually, by single laboratories or worldwide collaborations.

Published
2023

4. Morphological and functional properties distinguish the substance P and gastrin-releasing peptide subsets of excitatory interneuron in the spinal cord dorsal horn

Author

Dickie, Allen C, Bell, Andrew M, Iwagaki, Noboru, Polgár, Erika, Gutierrez-Mecinas, Maria, Kelly, Rosalind, Lyon, Heather, Turnbull, Kirsten, West, Steven J, Etlin, Alexander, Braz, Joao, Watanabe, Masahiko, Bennett, David LH, Basbaum, Allan I, Riddell, John S, and Todd, Andrew J

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Chronic Pain, Pain Research, Action Potentials, Analgesics, Animals, Capsaicin, Cholera Toxin, Extracellular Signal-Regulated MAP Kinases, Gastrin-Releasing Peptide, In Vitro Techniques, Interneurons, Luminescent Proteins, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neurotransmitter Agents, Patch-Clamp Techniques, Physical Stimulation, Protein Precursors, RNA, Messenger, Sensory System Agents, Spinal Cord Dorsal Horn, Statistics, Nonparametric, Substance P, Tachykinins, Transduction, Genetic, Glutamatergic interneuron, Radial cell, Central cell, GRP, Pain, Medical and Health Sciences, Psychology and Cognitive Sciences, Anesthesiology, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Excitatory interneurons account for the majority of neurons in the superficial dorsal horn, but despite their presumed contribution to pain and itch, there is still limited information about their organisation and function. We recently identified 2 populations of excitatory interneuron defined by expression of gastrin-releasing peptide (GRP) or substance P (SP). Here, we demonstrate that these cells show major differences in their morphological, electrophysiological, and pharmacological properties. Based on their somatodendritic morphology and firing patterns, we propose that the SP cells correspond to radial cells, which generally show delayed firing. By contrast, most GRP cells show transient or single-spike firing, and many are likely to correspond to the so-called transient central cells. Unlike the SP cells, few of the GRP cells had long propriospinal projections, suggesting that they are involved primarily in local processing. The 2 populations also differed in responses to neuromodulators, with most SP cells, but few GRP cells, responding to noradrenaline and 5-HT; the converse was true for responses to the μ-opioid agonist DAMGO. Although a recent study suggested that GRP cells are innervated by nociceptors and are strongly activated by noxious stimuli, we found that very few GRP cells receive direct synaptic input from TRPV1-expressing afferents, and that they seldom phosphorylate extracellular signal-regulated kinases in response to noxious stimuli. These findings indicate that the SP and GRP cells differentially process somatosensory information.

Published
2019

5. On the histochemical labelling and quantitative stereological assessment of synaptic puncta within the dorsal horn : with a focus on synaptic remodelling following a lesion to the peripheral nerve

Author

West, Steven J. and Bennett, David

Subjects
616.8
Abstract

Peripheral nerve injury often results in neuropathic pain, which is chronic, maladaptive, and hard to treat. Accompanying the injury to the peripheral nerve are a series of changes within the central nervous system. Understanding these changes and how they relate to the neuropathic condition is vital in driving evidence-based treatment strategies. Neuronal connectivity is widely believed to underlie many cognitive processes, and altered connectivity may underlie the development and maintenance of neuropathic pain. Here, a tractable method of analysing connectivity, via the histological marking and fluorescence imaging of synaptic puncta, was developed. This method utilised automated image processing methods, and developed a stereological filter for unbiased object measurement. Using this approach, different synaptic markers were analysed in the superficial dorsal horn of rodents, a key component in the reception and processing of somatosensory information. Analysing PSD95 and SynaptoPhysin fluorescent puncta in naive adult rodents revealed distinct puncta distributions in the dorsal horn, reflecting gross circuit formation throughout this region. Peripheral nerve lesion to aspects of the sciatic nerve of rodents resulted in a selective loss at 21 days post injury of PSD95 puncta from lamina II inner of the superficial dorsal horn, with Synaptophysin puncta remaining unchanged. These experiments were complemented by a transgenic approach, where eGFP was expressed exclusively and permanently in sensory neurons, which also revealed no loss of sensory neuron afferent input to the dorsal horn after nerve lesion up to 21 days post injury. Finally, the hypothesis that microglial cells may be driving this synapse loss was explored by treating animals with minocycline following peripheral nerve lesion, which did not interfere with the PSD95 puncta loss observed at 21 days post injury.

Published
2015

6. A modular architecture for organizing, processing and sharing neurophysiology data

Author

International Brain Laboratory, Bonacchi, Niccolò, Chapuis, Gaelle A, Churchland, Anne K, DeWitt, Eric EJ, Faulkner, Mayo, Harris, Kenneth D, Huntenburg, Julia M, Hunter, Max, Laranjeira, Inês C, Rossant, Cyrille, Sasaki, Maho, Schartner, Michael M, Shen, Shan, Steinmetz, Nicholas A, Walker, Edgar Y, West, Steven J, Winter, Olivier, and Wells, Miles J

Subjects
Technology, Neurophysiology, Cell Biology, Biological Sciences, Basic Behavioral and Social Science, Medical and Health Sciences, Biochemistry, Databases, Behavioral and Social Science, Laboratories, Molecular Biology, International Brain Laboratory, Factual, Developmental Biology, Biotechnology
Abstract

We describe an architecture for organizing, integrating and sharing neurophysiology data within a single laboratory or across a group of collaborators. It comprises a database linking data files to metadata and electronic laboratory notes; a module collecting data from multiple laboratories into one location; a protocol for searching and sharing data and a module for automatic analyses that populates a website. These modules can be used together or individually, by single laboratories or worldwide collaborations.

Published
2023

10. Boosting peripheral BDNF rescues impaired in vivo axonal transport in CMT2D mice

Author

Sleigh, James N., primary, Villarroel-Campos, David, additional, Surana, Sunaina, additional, Wickenden, Tahmina, additional, Tong, Yao, additional, Simkin, Rebecca L., additional, Vargas, Jose Norberto S., additional, Rhymes, Elena R., additional, Tosolini, Andrew P., additional, West, Steven J., additional, Zhang, Qian, additional, Yang, Xiang-Lei, additional, and Schiavo, Giampietro, additional

Published
2023
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11. Cognitive impairments in Down syndrome model associate with abnormal hippocampal and prefrontal dynamics and cytoarchitecture

Author

Muza, Phillip, primary, Bush, Daniel, additional, Pérez-González, Marta, additional, Zouhair, Ines, additional, Cleverley, Karen, additional, Llorian Sopena, Miriam, additional, Aoidi, Rifdat, additional, West, Steven J., additional, Good, Mark, additional, Tybulewicz, Victor L.J., additional, Walker, Matthew C., additional, Fisher, Elizabeth M.C., additional, and Chang, Pishan, additional

Published
2023
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14. A novel SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity

Author

Joyce, Peter I., Mcgoldrick, Philip, Saccon, Rachele A., Weber, William, Fratta, Pietro, West, Steven J., Zhu, Ning, Carter, Sarah, Phatak, Vinaya, Stewart, Michelle, Simon, Michelle, Kumar, Saumya, Heise, Ines, Bros-Facer, Virginie, Dick, James, Corrochano, Silvia, Stanford, Macdonnell J., Luong, Tu Vinh, Nolan, Patrick M., Meyer, Timothy, Brandner, Sebastian, Bennett, David L.H., Ozdinler, P. Hande, Greensmith, Linda, Fisher, Elizabeth M.C., and Acevedo-Arozena, Abraham

Published
2015
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19. Expression of green fluorescent protein defines a specific population of lamina II excitatory interneurons in the GRP::eGFP mouse

Author

Bell, Andrew M, Gutierrez-Mecinas, Maria, Stevenson, Anna, Casas-Benito, Adrian, Wildner, Hendrik, West, Steven J, Watanabe, Masahiko, Todd, Andrew J, Bell, Andrew M, Gutierrez-Mecinas, Maria, Stevenson, Anna, Casas-Benito, Adrian, Wildner, Hendrik, West, Steven J, Watanabe, Masahiko, and Todd, Andrew J

Abstract

Dorsal horn excitatory interneurons that express gastrin-releasing peptide (GRP) are part of the circuit for pruritogen-evoked itch. They have been extensively studied in a transgenic line in which enhanced green fluorescent protein (eGFP) is expressed under control of the Grp gene. The GRP-eGFP cells are separate from several other neurochemically-defined excitatory interneuron populations, and correspond to a class previously defined as transient central cells. However, mRNA for GRP is widely distributed among excitatory interneurons in superficial dorsal horn. Here we show that although Grp mRNA is present in several transcriptomically-defined populations, eGFP is restricted to a discrete subset of cells in the GRP::eGFP mouse, some of which express the neuromedin receptor 2 and likely belong to a cluster defined as Glut8. We show that these cells receive much of their excitatory synaptic input from MrgA3/MrgD-expressing nociceptive/pruritoceptive afferents and C-low threshold mechanoreceptors. Although the cells were not innervated by pruritoceptors expressing brain natriuretic peptide (BNP) most of them contained mRNA for NPR1, the receptor for BNP. In contrast, these cells received only ~ 10% of their excitatory input from other interneurons. These findings demonstrate that the GRP-eGFP cells constitute a discrete population of excitatory interneurons with a characteristic pattern of synaptic input.

Published
2020

23. Mars Surveyor Program '01 Mars Environmental Compatibility Assessment wet chemistry lab: a sensor array for chemical analysis of the Martian soil

Author

Kounaves, Samuel P, Lukow, Stefan R, Comeau, Brian P, Hecht, Michael H, Grannan-Feldman, Sabrina M, Manatt, Ken, West, Steven J, Wen, Xiaowen, Frant, Martin, and Gillette, Tim

Subjects
Lunar And Planetary Science And Exploration
Abstract

The Mars Environmental Compatibility Assessment (MECA) instrument was designed, built, and flight qualified for the now canceled MSP (Mars Surveyor Program) '01 Lander. The MECA package consisted of a microscope, electrometer, material patch plates, and a wet chemistry laboratory (WCL). The primary goal of MECA was to analyze the Martian soil (regolith) for possible hazards to future astronauts and to provide a better understanding of Martian regolith geochemistry. The purpose of the WCL was to analyze for a range of soluble ionic chemical species and electrochemical parameters. The heart of the WCL was a sensor array of electrochemically based ion-selective electrodes (ISE). After 20 months storage at -23 degrees C and subsequent extended freeze/thawing cycles, WCL sensors were evaluated to determine both their physical durability and analytical responses. A fractional factorial calibration of the sensors was used to obtain slope, intercept, and all necessary selectivity coefficients simultaneously for selected ISEs. This calibration was used to model five cation and three anion sensors. These data were subsequently used to determine concentrations of several ions in two soil leachate simulants (based on terrestrial seawater and hypothesized Mars brine) and four actual soil samples. The WCL results were compared to simulant and soil samples using ion chromatography and inductively coupled plasma optical emission spectroscopy. The results showed that flight qualification and prolonged low-temperature storage conditions had minimal effects on the sensors. In addition, the analytical optimization method provided quantitative and qualitative data that could be used to accurately identify the chemical composition of the simulants and soils. The WCL has the ability to provide data that can be used to "read" the chemical, geological, and climatic history of Mars, as well as the potential habitability of its regolith.

Published
2003
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24. Selective ionophore-based optical sensors for ammonia measurement in air

Author

West, Steven J., Ozawa, Satoshi, Seiler, Kurt, Tan, Susie S. S., and Simon, Wilhelm

Subjects
Ionophores -- Research, Ammonia -- Measurement, Sensors -- Usage, Chemistry
Abstract

Optical sensor systems composed of ionophores and chromoionophores that respectively display ammonium and hydrogen ion-selectivity can efficiently detect ammonia concentrations in sub-parts-per-billion volume. Optodes that are incorporated with tetrabromophenolphthalein (TBPE) and N,N'-dibenzyl-N,N'-diphenyl-1,2-(phenylenedioxy)diacetamide can detect ammonia from 0.002 to more than 100 ppm volume without humidity adjustment and sulfur-, nitrogen- and carbon-dioxide interference. However, in tests involving substantial amount of amines, a TBPE-valinomycin optode system is more applicable.

Published
1992

25. Immune or Genetic-Mediated Disruption of CASPR2 Causes Pain Hypersensitivity Due to Enhanced Primary Afferent Excitability

Author

Dawes, John M., Weir, Greg A., Middleton, Steven J., Patel, Ryan, Chisholm, Kim I., Pettingill, Philippa, Peck, Liam J., Sheridan, Joseph, Shakir, Akila, Jacobson, Leslie, Gutierrez-Mecinas, Maria, Galino, Jorge, Walcher, Jan, Kühnemund, Johannes, Kuehn, Hannah, Sanna, Maria D., Lang, Bethan, Clark, Alex J., Themistocleous, Andreas C., Iwagaki, Noboru, West, Steven J., Werynska, Karolina, Carroll, Liam, Trendafilova, Teodora, Menassa, David A., Giannoccaro, Maria P., Coutinho, Ester, Cervellini, Ilaria, Tewari, Damini, Leite, M. Isabel, Wildner, Hendrik, Zeilhofer, Hanns U., Peles, Elior, McMahon, Stephen B., Dickenson, Anthony H., Lewin, Gary R., Vincent, Angela, and Bennett, David L.

Subjects
nervous system
Abstract

Human autoantibodies to contactin-associated protein-like 2 (CASPR2) are often associated with neuropathic pain, and CASPR2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognized. Human CASPR2 autoantibodies, when injected into mice, were peripherally restricted and resulted in mechanical pain-related hypersensitivity in the absence of neural injury. We therefore investigated the mechanism by which CASPR2 modulates nociceptive function. Mice lacking CASPR2 (Cntnap2−/−) demonstrated enhanced pain-related hypersensitivity to noxious mechanical stimuli, heat, and algogens. Both primary afferent excitability and subsequent nociceptive transmission within the dorsal horn were increased in Cntnap2−/− mice. Either immune or genetic-mediated ablation of CASPR2 enhanced the excitability of DRG neurons in a cell-autonomous fashion through regulation of Kv1 channel expression at the soma membrane. This is the first example of passive transfer of an autoimmune peripheral neuropathic pain disorder and demonstrates that CASPR2 has a key role in regulating cell-intrinsic dorsal root ganglion (DRG) neuron excitability., Neuron, 97 (4)

Published
2018

27. Morphological and functional properties distinguish the substance P and gastrin-releasing peptide subsets of excitatory interneuron in the spinal cord dorsal horn

Author

Dickie, Allen C., primary, Bell, Andrew M., additional, Iwagaki, Noboru, additional, Polgár, Erika, additional, Gutierrez-Mecinas, Maria, additional, Kelly, Rosalind, additional, Lyon, Heather, additional, Turnbull, Kirsten, additional, West, Steven J., additional, Etlin, Alexander, additional, Braz, Joao, additional, Watanabe, Masahiko, additional, Bennett, David L.H., additional, Basbaum, Allan I., additional, Riddell, John S., additional, and Todd, Andrew J., additional

Published
2018
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28. Immune or Genetic-Mediated Disruption of CASPR2 Causes Pain Hypersensitivity Due to Enhanced Primary Afferent Excitability

Author

Dawes, John M., primary, Weir, Greg A., additional, Middleton, Steven J., additional, Patel, Ryan, additional, Chisholm, Kim I., additional, Pettingill, Philippa, additional, Peck, Liam J., additional, Sheridan, Joseph, additional, Shakir, Akila, additional, Jacobson, Leslie, additional, Gutierrez-Mecinas, Maria, additional, Galino, Jorge, additional, Walcher, Jan, additional, Kühnemund, Johannes, additional, Kuehn, Hannah, additional, Sanna, Maria D., additional, Lang, Bethan, additional, Clark, Alex J., additional, Themistocleous, Andreas C., additional, Iwagaki, Noboru, additional, West, Steven J., additional, Werynska, Karolina, additional, Carroll, Liam, additional, Trendafilova, Teodora, additional, Menassa, David A., additional, Giannoccaro, Maria Pia, additional, Coutinho, Ester, additional, Cervellini, Ilaria, additional, Tewari, Damini, additional, Buckley, Camilla, additional, Leite, M. Isabel, additional, Wildner, Hendrik, additional, Zeilhofer, Hanns Ulrich, additional, Peles, Elior, additional, Todd, Andrew J., additional, McMahon, Stephen B., additional, Dickenson, Anthony H., additional, Lewin, Gary R., additional, Vincent, Angela, additional, and Bennett, David L., additional

Published
2018
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31. A novel SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity

Author

Joyce, Peter I., primary, Mcgoldrick, Philip, additional, Saccon, Rachele A., additional, Weber, William, additional, Fratta, Pietro, additional, West, Steven J., additional, Zhu, Ning, additional, Carter, Sarah, additional, Phatak, Vinaya, additional, Stewart, Michelle, additional, Simon, Michelle, additional, Kumar, Saumya, additional, Heise, Ines, additional, Bros-Facer, Virginie, additional, Dick, James, additional, Corrochano, Silvia, additional, Stanford, Macdonnell J., additional, Luong, Tu Vinh, additional, Nolan, Patrick M., additional, Meyer, Timothy, additional, Brandner, Sebastian, additional, Bennett, David L.H., additional, Ozdinler, P. Hande, additional, Greensmith, Linda, additional, Fisher, Elizabeth M.C., additional, and Acevedo-Arozena, Abraham, additional

Published
2014
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32. The MECA Wet Chemistry Laboratory on the 2007 Phoenix Mars Scout Lander

Author

Kounaves, Samuel P., primary, Hecht, Michael H., additional, West, Steven J., additional, Morookian, John‐Michael, additional, Young, Suzanne M. M., additional, Quinn, Richard, additional, Grunthaner, Paula, additional, Wen, Xiaowen, additional, Weilert, Mark, additional, Cable, Casey A., additional, Fisher, Anita, additional, Gospodinova, Kalina, additional, Kapit, Jason, additional, Stroble, Shannon, additional, Hsu, Po‐Chang, additional, Clark, Benton C., additional, Ming, Douglas W., additional, and Smith, Peter H., additional

Published
2009
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38. Interactive data exploration websites for large-scale electrophysiology.

Author

Birman D, Chapuis G, Faulkner M, Rossant C, Benson J, Catarino JA, Churchland AK, Hu F, Huntenburg JM, Khanal A, Krasniak C, Lau PYP, Meijer GT, Miska NJ, Noel JP, Pan-Vazquez A, Roth N, Schartner M, Socha KZ, Steinmetz NA, Urai AE, Wells MJ, West SJ, and Winter O

Abstract

Methodological advances in neuroscience have enabled the collection of massive datasets which demand innovative approaches for scientific communication. Existing platforms for data storage lack intuitive tools for data exploration, limiting our ability to interact effectively with these brain-wide datasets. We introduce two public websites: (Data and Atlas) developed for the International Brain Laboratory which provide access to millions of behavioral trials and hundreds of thousands of individual neurons. These interfaces allow users to discover both the raw and processed brain-wide data released by the IBL at the scale of the whole brain, individual sessions, trials, and neurons. By hosting these data interfaces as websites they are available cross-platform with no installation. By releasing each site's code as a modular open-source framework, other researchers can easily develop their own web interfaces and explore their own data. As neuroscience datasets continue to expand, customizable web interfaces offer a glimpse into a future of streamlined data exploration and act as blueprints for future tools.

Published
2024
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39. Pinpoint: trajectory planning for multi-probe electrophysiology and injections in an interactive web-based 3D environment.

Author

Birman D, Yang KJ, West SJ, Karsh B, Browning Y, Siegle JH, and Steinmetz NA

Abstract

Targeting deep brain structures during electrophysiology and injections requires intensive training and expertise. Even with experience, researchers often can't be certain that a probe is placed precisely in a target location and this complexity scales with the number of simultaneous probes used in an experiment. Here, we present Pinpoint , open-source software that allows for interactive exploration of stereotaxic insertion plans. Once an insertion plan is created, Pinpoint allows users to save these online and share them with collaborators. 3D modeling tools allow users to explore their insertions alongside rig and implant hardware and ensure plans are physically possible. Probes in Pinpoint can be linked to electronic micro-manipulators allowing real-time visualization of current brain region targets alongside neural data. In addition, Pinpoint can control manipulators to automate and parallelize the insertion process. Compared to previously available software, Pinpoint's easy access through web browsers, extensive features, and real-time experiment integration enable more efficient and reproducible recordings.

Published
2023
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