Article
Biology
Peter R. Strege, Luke M. Cowan, Constanza Alcaino, Amelia Mazzone, Christopher A. Ahern, Lorin S. Milescu, Gianrico Farrugia, Arthur Beyder
Summary: Shear stress and patch suction can reversibly alter the kinetic properties and maximum current of NaChBac, suggesting it is mechanosensitive. Structural analysis reveals a large displacement of the intracellular gate, supporting the proposed mechanosensitive mechanism.
Proceedings Paper
Computer Science, Artificial Intelligence
Gema I. Vera Gonzalez, Phatsimo O. Kgwarae, Simon R. Schultz
Summary: We developed an automated quad-channel patch-clamp technology platform that can perform blind and two-photon targeted robotically automated patching for ex vivo brain slice electrophysiology. The success rates for seal formation in two-photon targeted and blind modes were 54% and 68% respectively. In 50% of targeted trials, multiple simultaneous recordings were obtained. For blind mode, most trials resulted in dual or triple recordings. This robot represents a milestone towards a true in vivo targeted robotic multi-patching technology platform, enabling studies on the function and connectivity patterns of primary and secondary cell types.
2023 11TH INTERNATIONAL IEEE/EMBS CONFERENCE ON NEURAL ENGINEERING, NER
(2023)
Article
Gastroenterology & Hepatology
Zhiling Li, Werend Boesmans, Youcef Kazwiny, Marlene M. Hao, Pieter Vanden Berghe
Summary: Live calcium imaging is a valuable tool for simultaneous analysis of neuronal activity. This study investigated how enteric neurons respond to different modes of depolarization using electrophysiology and calcium imaging techniques. The research found that single action potentials can elicit calcium transients in both AH-neurons and S-neurons, and nicotinic acetylcholine receptor stimulation can be used to distinguish between these two classes.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Chemistry, Medicinal
Juan Antonio Contreras Vite, Carlos Vega Valle, Happi Biekeu Mbem, Sarah-Maude Boivin, Robert Dumaine
Summary: Lamotrigine is commonly used for treating bipolar disorder and epilepsy. The US FDA has recently issued a warning regarding the drug's potential to cause conduction anomalies and Brugada syndrome in epileptic patients. In this study, researchers used patch clamp technique on rat cardiomyocytes to investigate the effect of Lamotrigine on cardiac sodium current (I-Na). The results showed that Lamotrigine inhibited I-Na peak amplitude, reduced cardiac excitability, and prolonged the action potential refractory period in epileptic rats.
Article
Biochemistry & Molecular Biology
Karl Josef Foehr, Michael Rapp, Michael Fauler, Thomas Zimmer, Bettina Jungwirth, David Alexander Christian Messerer
Summary: Aripiprazole has been identified as a potent blocker of the dominant voltage-gated sodium channel of heart muscle. Its interactions with the channel differ depending on the state, with weaker affinity for the resting state and stronger affinity for the inactivated state.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Damian C. Bell, Luigi Leanza, Saverio Gentile, Daniel R. Sauter
Summary: Ion channels play key roles in various physiological processes, and their dysfunction can lead to channelopathies, including cancer. The field of ion channel and cancer research has rapidly grown in the past two decades, allowing us to gain deeper insights into the mechanisms of ion channels in cancer and develop therapeutic interventions.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Anesthesiology
Tyler J. Browne, Kelly M. Smith, Mark A. Gradwell, Jacqueline A. Iredale, Christopher V. Dayas, Robert J. Callister, David I. Hughes, Brett A. Graham
Summary: Projection neurons in the spinal dorsal horn play a crucial role in relaying sensory information to higher brain centres, receiving inputs from the periphery, brain, and local circuits. Recent studies in transgenic mice have provided insights into dorsal horn circuitry, while information on projection neurons is mainly based on previous studies in monkey, cat, and rat. The study on mouse spinoparabrachial projection neurons identified distinct subpopulations in lamina I based on electrophysiological properties, suggesting different sensory signalling features. Additionally, the research revealed novel information on deeper lamina SPBNs, showing different sensory codes destined for the PBN and their contribution to excitatory input in dorsal horn circuits.
Article
Neurosciences
Walter Francesconi, Fulvia Berton, Valentina Olivera-Pasilio, Joanna Dabrowska
Summary: The study reveals that oxytocin has distinct effects on different types of neurons in the dorsolateral bed nucleus of the stria terminalis. It selectively excites some neurons while inhibiting others, potentially facilitating conditioned fear by suppressing inter-neuronal interactions.
Article
Biochemical Research Methods
Christopher Miranda, Madeleine R. Howell, Joel F. Lusk, Ethan Marschall, Jarrett Eshima, Trent Anderson, Barbara S. Smith
Summary: This study demonstrates a method of guiding glass micropipette electrodes to neurons by collecting fluorescence at the aperture using an intra-electrode tapered optical fiber. The use of a tapered fiber for excitation and collection of fluorescence at the micropipette tip allows for targeted robotic approach to labeled neurons independent of microscopy.
BIOMEDICAL OPTICS EXPRESS
(2021)
Article
Neurosciences
Marcela Lipovsek, Cedric Bardy, Cathryn R. Cadwell, Kristen Hadley, Dmitry Kobak, Shreejoy J. Tripathy
Summary: Patch-seq is a revolutionary technique in neuroscience that integrates morphology, physiology, and gene expression data to study neuronal biology comprehensively. It enables targeted study of specific neuronal populations, compilation of multimodal cell type atlases, and investigation of the molecular basis of morphologic and functional diversity. This technique has the potential for further technical development and implementation in various research areas to directly link gene expression to brain function.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Pharmacology & Pharmacy
Shirin Ahmadi, Melisa Benard-Valle, Kim Boddum, Fernanda C. Cardoso, Glenn F. King, Andreas Hougaard Laustsen, Anne Ljungars
Summary: Ion channels are crucial for various physiological processes. Venomous creatures exploit ion channels by producing toxins that target them, leading to dysregulation which can cause severe complications in humans. However, the discovery of selective venom toxins has contributed to the development of drugs for envenoming and ion channel-related diseases.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Mark L. Dallas, Damian Bell
Summary: It is clear that APC technology has significantly advanced drug discovery programs, particularly in the fields of neuroscience and cardiovascular research. The challenge for the future lies in keeping up with fundamental research and improving the translation of the large datasets obtained.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Nunzio Iraci, Carmine Ostacolo, Alicia Medina-Peris, Tania Ciaglia, Anton M. Novoselov, Andrea Altieri, David Cabanero, Asia Fernandez-Carvajal, Pietro Campiglia, Isabel Gomez-Monterrey, Alessia Bertamino, Alexander V. Kurkin
Summary: Transient receptor potential melastatin type 8 (TRPM8) is an important target for treating various physiological and pathological processes. In this study, a total of twenty-one potentially TRPM8 antagonist compounds were identified through in silico screening and validated using calcium fluorometric assays. Four compounds were found to be selective TRPM8 antagonists, with two of them also acting as TRPM8/TRPV1 modulators. The most potent compound (BB 0322703) showed significant pharmacological efficacy in in vivo experiments. These findings provide valuable insights for drug discovery and further pharmacological investigations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Travis A. Hage, Alice Bosma-Moody, Christopher A. Baker, Megan B. Kratz, Luke Campagnola, Tim Jarsky, Hongkui Zeng, Gabe J. Murphy
Summary: Understanding cortical microcircuits requires thorough measurement of physiological properties of synaptic connections formed within and between diverse subclasses of neurons. In this study, the researchers combined optogenetic stimulation and multicellular recording to deeply characterize intralaminar and translaminar monosynaptic connections in the mouse visual cortex. They measured the reliability and specificity of the optogenetic stimulation and verified the connectivity measurements using paired recordings and targeted patching. The study revealed the abundance, spatial profiles, strength, and short-term dynamics of excitatory and inhibitory synaptic connections between genetically defined presynaptic populations. They found that layer 4 excitatory neurons and interneurons within L2/3 were the most common sources of input to L2/3 pyramidal cells, but also observed excitatory connections from layer 5 intratelencephalic neurons and translaminar inhibition from multiple interneuron subclasses.
Article
Multidisciplinary Sciences
Jerome Montnach, Maxime Lorenzini, Adrien Lesage, Isabelle Simon, Sebastien Nicolas, Eleonore Moreau, Celine Marionneau, Isabelle Baro, Michel De Waard, Gildas Loussouarn
Summary: The whole-cell voltage-clamp technique requires consideration of the impact of current amplitude on data accuracy, especially in high throughput patch-clamp applications to prevent inaccuracies. Mathematical kinetic models can predict how large current amplitudes and series resistance artifacts affect voltage-dependent activation and inactivation processes, providing simple guidelines for practice.
SCIENTIFIC REPORTS
(2021)
Article
Computer Science, Artificial Intelligence
Romain D. Caze, Sarah Jarvis, Amanda J. Foust, Simon R. Schultz
NEURAL COMPUTATION
(2017)
Article
Engineering, Biomedical
Renaud Schuck, Mary Ann Go, Stefania Garasto, Stephanie Reynolds, Pier Luigi Dragotti, Simon R. Schultz
JOURNAL OF NEURAL ENGINEERING
(2018)
Article
Multidisciplinary Sciences
Joseph Sollini, Gaelle A. Chapuis, Claudia Clopath, Paul Chadderton
NATURE COMMUNICATIONS
(2018)
Article
Biochemical Research Methods
Sarah Jarvis, Konstantin Nikolic, Simon R. Schultz
PLOS COMPUTATIONAL BIOLOGY
(2018)
Article
Cell Biology
Jun Ho Song, Diana Lucaci, Ioana Calangiu, Matthew T. C. Brown, Jin Sung Park, Jinhyun Kim, Stephen G. Brickley, Paul Chadderton
Article
Behavioral Sciences
Gaelle A. Chapuis, Paul T. Chadderton
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2018)
Article
Physics, Applied
Navjeevan S. Soor, Peter Quicke, Carmel L. Howe, Kuin T. Pang, Mark A. A. Neil, Simon R. Schultz, Amanda J. Foust
JOURNAL OF PHYSICS D-APPLIED PHYSICS
(2019)
Article
Engineering, Biomedical
Carl H. Lubba, Zhonghua Ouyang, Nick S. Jones, Tim M. Bruns, Simon R. Schultz
Summary: This study characterizes the encoding of bladder pressure by sensory fibers and explores a decoding paradigm based on information theory. The research demonstrates that different types of bladder neurons offer reliability and high information rates through redundancy and semi-independence.
JOURNAL OF NEURAL ENGINEERING
(2021)
Review
Biology
Ensor Rafael Palacios, Conor Houghton, Paul Chadderton
Summary: The review discusses the possible contribution of inhibition to the encoding of precision of neural representations in the granular layer of the cerebellar cortex, emphasizing the critical role of Golgi cells in shaping information transmission downstream to Purkinje cells.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2021)
Article
Multidisciplinary Sciences
Caroline T. Golden, Paul Chadderton
Summary: This study investigated the neural effects of psilocybin in awake mice using multi-unit extracellular recordings. The findings suggest that psilocybin reduces the power of low frequency oscillations, increases overall firing rates of neurons, and desynchronizes local neural activity.
SCIENTIFIC REPORTS
(2022)
Article
Biochemical Research Methods
Chris Barkus, Caroline Bergmann, Tiago Branco, Matteo Carandini, Paul T. Chadderton, Gregorio L. Galinanes, Gary Gilmour, Daniel Huber, John R. Huxter, Adil G. Khan, Andrew J. King, Miguel Maravall, Tina O'Mahony, C. Ian Ragan, Emma S. J. Robinson, Andreas T. Schaefer, Simon R. Schultz, Frank Sengpiel, Mark J. Prescott
Summary: This article summarizes the current practices of head fixation in research, providing recommendations to improve animal welfare and data quality. It also discusses alternative methods that do not require restraint.
JOURNAL OF NEUROSCIENCE METHODS
(2022)
Review
Mathematical & Computational Biology
Rufus Mitchell-Heggs, Selgfred Prado, Giuseppe P. Gava, Mary Ann Go, Simon R. Schultz
Summary: Recent developments in experimental neuroscience have enabled the simultaneous recording of activity from thousands of neurons. Neural manifold learning is a popular approach that takes advantage of the low-dimensional dynamics of neural activity to uncover neural circuits' links to cognitive function. This paper reviews various linear and non-linear approaches to neural manifold learning, compares their advantages and disadvantages in analyzing neural data, and applies them to different datasets to demonstrate their applicability. The results show that both linear and non-linear methods produce similar results in many cases, with non-linear methods being more effective in cases with higher behavioral complexity. The application of these methods to a mouse model of Alzheimer's Disease suggests their potential in understanding the circuit-level consequences of neurological disorders.
JOURNAL OF COMPUTATIONAL NEUROSCIENCE
(2023)
Article
Neurosciences
Diana Lucaci, Xiao Yu, Paul Chadderton, William Wisden, Stephen G. Brickley
Summary: We investigated the effects of histamine and GABA release from TMN axons projecting to the PFC on circuit processing. Histamine stimulated fast-spiking interneurons, while released GABA enhanced tonic inhibition on PyrNs. Histamine-induced gain changes were blocked by histamine receptor antagonists, while GABA-induced gain changes were blocked by GABAA receptor antagonists. The GABA modulation of PyrN excitability by TMNHDC axons increased significantly in older mice, potentially enhancing information processing and maintaining cognition in aging individuals.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Stephanie Reynolds, Therese Abrahamsson, Renaud Schuck, P. Jesper Sjostrom, Simon R. Schultz, Pier Luigi Dragotti