DigiBrain

• Ager-Wick, Eirill; Maugars, Gersende Marie Aimee; von Krogh, Kristine; Fontaine, Romain; Weltzien, Finn-Arne & Henkel, Christiaan (2023). An RNA-seq time series of the medaka pituitary gland during sexual maturation. Scientific Data. ISSN 2052-4463. doi: 10.1038/s41597-023-01967-w.
• Skaar, Jan-Eirik Welle; Haug, Nicolai; Stasik, Alexander Johannes; Einevoll, Gaute & Tøndel, Kristin (2023). Metamodelling of a two-population spiking neural network. PLoS Computational Biology. ISSN 1553-734X. 19(11). doi: 10.1371/journal.pcbi.1011625. Full text in Research Archive
• Akkouh, Ibrahim Ahmed; Ueland, Thor; Szabo, Attila; Hughes, Timothy; Smeland, Olav Bjerkehagen & Andreassen, Ole [Show all 8 contributors for this article] (2023). Longitudinal Transcriptomic Analysis of Human Cortical Spheroids Identifies Axonal Dysregulation in the Prenatal Brain as a Mediator of Genetic Risk for Schizophrenia. Biological Psychiatry. ISSN 0006-3223. 0, p. 1–12. doi: 10.1016/j.biopsych.2023.08.017. Full text in Research Archive
• Mäki-Marttunen, Tuomo & Mäki-Marttunen, Verónica (2022). Excitatory and inhibitory effects of HCN channel modulation on excitability of layer V pyramidal cells. PLoS Computational Biology. ISSN 1553-734X. 18(9). doi: 10.1371/journal.pcbi.1010506. Full text in Research Archive
• Koivumäki, Jussi T.; Hoffman, Johan; Maleckar, Mary Margot Catherine; Einevoll, Gaute & Sundnes, Joakim (2022). Computational cardiac physiology for new modelers: Origins, foundations, and future. Acta Physiologica. ISSN 1748-1708. 236. doi: 10.1111/apha.13865. Show summary

  Mathematical models of the cardiovascular system have come a long way since they were first introduced in the early 19th century. Driven by a rapid develop-ment of experimental techniques, numerical methods, and computer hardware, detailed models that describe physical scales from the molecular level up to or-gans and organ systems have been derived and used for physiological research. Mathematical and computational models can be seen as condensed and quantita-tive formulations of extensive physiological knowledge and are used for formulat-ing and testing hypotheses, interpreting and directing experimental research, and have contributed substantially to our understanding of cardiovascular physiol-ogy. However, in spite of the strengths of mathematics to precisely describe com-plex relationships and the obvious need for the mathematical and computational models to be informed by experimental data, there still exist considerable barriers between experimental and computational physiological research. In this review, we present a historical overview of the development of mathematical and com-putational models in cardiovascular physiology, including the current state of the art. We further argue why a tighter integration is needed between experimental and computational scientists in physiology, and point out important obstacles and challenges that must be overcome in order to fully realize the synergy of ex-perimental and computational physiological research.

• Royan, Muhammad Rahmad; Siddique, Khadeeja; Csucs, Gergely; Puchades, Maja ; Nourizadeh-Lillabadi, Rasoul & Bjaalie, Jan G. [Show all 9 contributors for this article] (2021). 3D Atlas of the Pituitary Gland of the Model Fish Medaka (Oryzias latipes). Frontiers in Endocrinology. ISSN 1664-2392. 12. doi: 10.3389/fendo.2021.719843. Full text in Research Archive Show summary

  In vertebrates, the anterior pituitary plays a crucial role in regulating several essential physiological processes via the secretion of at least seven peptide hormones by different endocrine cell types. Comparative and comprehensive knowledge of the spatial distribution of those endocrine cell types is required to better understand their physiological functions. Using medaka as a model and several combinations of multicolor fluorescence in situ hybridization, we present the first 3D atlas revealing the glandwide distribution of seven endocrine cell populations: lactotropes, thyrotropes, Lh and Fsh gonadotropes, somatotropes, and pomca-expressing cells (corticotropes and melanotropes) in the anterior pituitary of a teleost fish. By combining in situ hybridization and immunofluorescence techniques, we deciphered the location of corticotropes and melanotropes within the pomca-expressing cell population. The 3D localization approach reveals sexual dimorphism of tshba-, pomca-, and lhb-expressing cells in the adult medaka pituitary. Finally, we show the existence of bi-hormonal cells coexpressing lhb-fshb, fshb-tshba and lhb-sl using single-cell transcriptomics analysis and in situ hybridization. This study offers a solid basis for future comparative studies of the teleost pituitary and its functional plasticity.

• Lepperød, Mikkel Elle; Christensen, Ane Charlotte; Lensjø, Kristian Kinden; Buccino, Alessio Paolo; Yu, Jai & Fyhn, Marianne [Show all 7 contributors for this article] (2021). Optogenetic pacing of medial septum parvalbumin-positive cells disrupts temporal but not spatial firing in grid cells. Science Advances. ISSN 2375-2548. 7(19). doi: 10.1126/sciadv.abd5684. Full text in Research Archive
• Christensen, Ane Charlotte; Lensjø, Kristian Kinden; Lepperød, Mikkel Elle; Dragly, Svenn-Arne; Sutterud, Hallvard & Blackstad, Jan Sigurd [Show all 8 contributors for this article] (2021). Perineuronal nets stabilize the grid cell network. Nature Communications. ISSN 2041-1723. 12. doi: 10.1038/s41467-020-20241-w. Full text in Research Archive
• Rødevand, Linn ; Bahrami, Shahram; Frei, Oleksandr; Lin, Aihua; Gani, Osman & Shadrin, Alexey A. [Show all 18 contributors for this article] (2021). Polygenic overlap and shared genetic loci between loneliness, severe mental disorders, and cardiovascular disease risk factors suggest shared molecular mechanisms. Translational Psychiatry. ISSN 2158-3188. 11(1). doi: 10.1038/s41398-020-01142-4. Full text in Research Archive Show summary

  Clinical and epidemiological evidence suggest that loneliness is associated with severe mental disorders (SMDs) and increases the risk of cardiovascular disease (CVD). However, the mechanisms underlying the relationship between loneliness, SMDs, and CVD risk factors remain unknown. Here we explored overlapping genetic architecture and genetic loci shared between SMDs, loneliness, and CVD risk factors. We analyzed large independent genome-wide association study data on schizophrenia (SCZ), bipolar disorder (BD), major depression (MD), loneliness and CVD risk factors using bivariate causal mixture mode (MiXeR), which estimates the total amount of shared variants, and conditional false discovery rate to evaluate overlap in specific loci. We observed substantial genetic overlap between SMDs, loneliness and CVD risk factors, beyond genetic correlation. We identified 149 loci jointly associated with loneliness and SMDs (MD n = 67, SCZ n = 54, and BD n = 28), and 55 distinct loci jointly associated with loneliness and CVD risk factors. A total of 153 novel loneliness loci were found. Most of the shared loci possessed concordant effect directions, suggesting that genetic risk for loneliness may increase the risk of both SMDs and CVD. Functional analyses of the shared loci implicated biological processes related to the brain, metabolic processes, chromatin and immune system. Altogether, the study revealed polygenic overlap between loneliness, SMDs and CVD risk factors, providing new insights into their shared genetic architecture and common genetic mechanisms.

• Engh, John; Ueland, Thor; Agartz, Ingrid; Andreou, Dimitrios; Aukrust, Pål & Boye, Birgitte [Show all 27 contributors for this article] (2021). Plasma Levels of the Cytokines B Cell-Activating Factor (BAFF) and A Proliferation-Inducing Ligand (APRIL) in Schizophrenia, Bipolar, and Major Depressive Disorder: A Cross Sectional, Multisite Study. Schizophrenia Bulletin. ISSN 0586-7614. 48(1), p. 37–46. doi: 10.1093/schbul/sbab106. Show summary

  Background Immune dysfunction has been implicated in the pathogenesis of schizophrenia and other nonaffective psychosis (SCZ), bipolar spectrum disorder (BIP) and major depressive disorder (MDD). The cytokines B cell-activating factor (BAFF) and A proliferation-inducing ligand (APRIL) belong to the tumor necrosis factor (TNF) super family and are essential in orchestrating immune responses. Abnormal levels of BAFF and APRIL have been found in autoimmune diseases with CNS affection. Methods We investigated if plasma levels of BAFF and APRIL differed between patients with SCZ, BIP, and MDD with psychotic symptoms (n = 2009) and healthy control subjects (HC, n = 1212), and tested for associations with psychotic symptom load, controlling for sociodemographic status, antipsychotic and other psychotropic medication, smoking, body-mass-index, and high sensitivity CRP. Results Plasma APRIL level was significantly lower across all patient groups compared to HC (P < .001; Cohen’s d = 0.33), and in SCZ compared to HC (P < .001; d = 0.28) and in BIP compared to HC (P < .001; d = 0.37). Lower plasma APRIL was associated with higher psychotic symptom load with nominal significance (P = .017), but not with any other clinical characteristics. Plasma BAFF was not significantly different across patient groups vs HC, but significantly higher in BIP compared to HC (P = .040; d = 0.12) and SCZ (P = .027; d = 0.10). Conclusions These results show aberrant levels of BAFF and APRIL and association with psychotic symptoms in patients with SCZ and BIP. This suggest that dysregulation of the TNF system, mediated by BAFF and APRIL, is involved in the pathophysiology of psychotic disorders.

• Sætra, Marte Julie; Einevoll, Gaute & Halnes, Geir (2021). An electrodiffusive neuron-extracellular-glia model for exploring the genesis of slow potentials in the brain. PLoS Computational Biology. ISSN 1553-734X. 17(7). doi: 10.1371/journal.pcbi.1008143. Full text in Research Archive Show summary

  Within the computational neuroscience community, there has been a focus on simulating the electrical activity of neurons, while other components of brain tissue, such as glia cells and the extracellular space, are often neglected. Standard models of extracellular potentials are based on a combination of multicompartmental models describing neural electrodynamics and volume conductor theory. Such models cannot be used to simulate the slow components of extracellular potentials, which depend on ion concentration dynamics, and the effect that this has on extracellular diffusion potentials and glial buffering currents. We here present the electrodiffusive neuron-extracellular-glia (edNEG) model, which we believe is the first model to combine compartmental neuron modeling with an electrodiffusive framework for intra- and extracellular ion concentration dynamics in a local piece of neuro-glial brain tissue. The edNEG model (i) keeps track of all intraneuronal, intraglial, and extracellular ion concentrations and electrical potentials, (ii) accounts for action potentials and dendritic calcium spikes in neurons, (iii) contains a neuronal and glial homeostatic machinery that gives physiologically realistic ion concentration dynamics, (iv) accounts for electrodiffusive transmembrane, intracellular, and extracellular ionic movements, and (v) accounts for glial and neuronal swelling caused by osmotic transmembrane pressure gradients. The edNEG model accounts for the concentration-dependent effects on ECS potentials that the standard models neglect. Using the edNEG model, we analyze these effects by splitting the extracellular potential into three components: one due to neural sink/source configurations, one due to glial sink/source configurations, and one due to extracellular diffusive currents. Through a series of simulations, we analyze the roles played by the various components and how they interact in generating the total slow potential. We conclude that the three components are of comparable magnitude and that the stimulus conditions determine which of the components that dominate.

• Lehr, Andrew; Kumar, Arvind; Tezlaff, Christian; Hafting, Torkel; Fyhn, Marianne & Stöber, Tristan Manfred (2021). CA2 beyond social memory: Evidence for a fundamental role in hippocampal information processing. Neuroscience and Biobehavioral Reviews. ISSN 0149-7634. 126, p. 398–412. doi: 10.1016/j.neubiorev.2021.03.020. Full text in Research Archive Show summary

  Hippocampal region CA2 has received increased attention due to its importance in social recognition memory. While its specific function remains to be identified, there are indications that CA2 plays a major role in a variety of situations, widely extending beyond social memory. In this targeted review, we highlight lines of research which have begun to converge on a more fundamental role for CA2 in hippocampus-dependent memory processing. We discuss recent proposals that speak to the computations CA2 may perform within the hippocampal circuit.

• Mäki-Marttunen, Tuomo; Iannella, Nicolangelo Libero; Edwards, Andrew; Einevoll, Gaute & Blackwell, Kim T. (2020). A unified computational model for cortical post-synaptic plasticity. eLIFE. ISSN 2050-084X. 9, p. 1–37. doi: 10.7554/eLife.55714. Full text in Research Archive
• Stöber, Tristan Manfred; Lehr, Andrew B; Hafting, Torkel; Kumar, Arvind & Fyhn, Marianne (2020). Selective neuromodulation and mutual inhibition within the CA3-CA2 system can prioritize sequences for replay. Hippocampus. ISSN 1050-9631. doi: 10.1002/hipo.23256. Full text in Research Archive
• Sætra, Marte Julie; Solbrå, Andreas Våvang; Devor, Anna; Sakadžić, Sava; Dale, Anders M. & Einevoll, Gaute (2020). Spatially Resolved Estimation of Metabolic Oxygen Consumption From Optical Measurements in Cortex. Neurophotonics. ISSN 2329-423X. 7(3). doi: 10.1117/1.NPh.7.3.035005. Full text in Research Archive
• Fontaine, Romain; Ager-Wick, Eirill; Hodne, Kjetil & Weltzien, Finn-Arne (2020). Plasticity in medaka gonadotropes via cell proliferation and phenotypic conversion. Journal of Endocrinology. ISSN 0022-0795. 245(1), p. 21–37. doi: 10.1530/JOE-19-0405. Full text in Research Archive
• Sætra, Marte Julie; Einevoll, Gaute & Halnes, Geir (2020). An electrodiffusive, ion conserving Pinsky-Rinzel model with homeostatic mechanisms. PLoS Computational Biology. ISSN 1553-734X. 16(4), p. 1–36. doi: 10.1371/journal.pcbi.1007661. Full text in Research Archive
• Burow, Susann; Mizrahi, Naama; Maugars, Gersende Marie Aimee; von Krogh, Kristine; Nourizadeh-Lillabadi, Rasoul & Hollander-Cohen, Lian [Show all 10 contributors for this article] (2020). Characterization of gonadotropin receptors Fshr and Lhr in Japanese medaka, Oryzias latipes. General and Comparative Endocrinology. ISSN 0016-6480. 285, p. 1–16. doi: 10.1016/j.ygcen.2019.113276. Full text in Research Archive
• Lepperød, Mikkel Elle; Dragly, Svenn-Arne; Buccino, Alessio Paolo; Mobarhan, Milad; Malthe-Sørenssen, Anders & Hafting, Torkel [Show all 7 contributors for this article] (2020). Experimental Pipeline (Expipe): A Lightweight Data Management Platform to Simplify the Steps From Experiment to Data Analysis. Frontiers in Neuroinformatics. ISSN 1662-5196. 14. doi: 10.3389/fninf.2020.00030. Full text in Research Archive Show summary

  As experimental neuroscience is moving toward more integrative approaches, with a variety of acquisition techniques covering multiple spatiotemporal scales, data management is becoming increasingly challenging for neuroscience laboratories. Often, datasets are too large to practically be stored on a laptop or a workstation. The ability to query metadata collections without retrieving complete datasets is therefore critical to efficiently perform new analyses and explore the data. At the same time, new experimental paradigms lead to constantly changing specifications for the metadata to be stored. Despite this, there is currently a serious lack of agile software tools for data management in neuroscience laboratories. To meet this need, we have developed Expipe, a lightweight data management framework that simplifies the steps from experiment to data analysis. Expipe provides the functionality to store and organize experimental data and metadata for easy retrieval in exploration and analysis throughout the experimental pipeline. It is flexible in terms of defining the metadata to store and aims to solve the storage and retrieval challenges of data/metadata due to ever changing experimental pipelines. Due to its simplicity and lightweight design, we envision Expipe as an easy-to-use data management solution for experimental laboratories, that can improve provenance, reproducibility, and sharing of scientific projects.

• Mäki-Marttunen, Tuomo; Krull, Florian; Bettella, Francesco; Hagen, Espen; Næss, Solveig & Ness, Torbjørn V [Show all 16 contributors for this article] (2019). Alterations in schizophrenia-associated genes can lead to increased power in delta oscillations. Cerebral Cortex. ISSN 1047-3211. 29(2), p. 875–891. doi: 10.1093/cercor/bhy291. Full text in Research Archive
• Lee, Phil H.; Antilla, Verneri; Won, Hyejung; Feng, Yen-Chen A.; Rosenthal, Jacob & Zhu, Zhaozhong [Show all 66 contributors for this article] (2019). Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders. Cell. ISSN 0092-8674. 179(7), p. 1469–1482. doi: 10.1016/j.cell.2019.11.020. Full text in Research Archive
• Tennøe, Simen; Hodne, Kjetil; Haug, Trude; Weltzien, Finn-Arne; Einevoll, Gaute & Halnes, Geir (2019). [Re] Fast-Activating Voltage- and Calcium-Dependent Potassium (BK) Conductance Promotes Bursting in Pituitary Cells: A Dynamic Clamp Study. ReScience. ISSN 2430-3658. 5(1). doi: 10.5281/zenodo.2611252. Full text in Research Archive
• Fontaine, Romain David & Weltzien, Finn-Arne (2019). Labeling of blood vessels in the teleost brain and pituitary using cardiac perfusion with a dil-fixative. Journal of Visualized Experiments. ISSN 1940-087X. 148. doi: 10.3791/59768. Show summary

  Blood vessels innervate all tissues in vertebrates, enabling their survival by providing the necessary nutrients, oxygen, and hormonal signals. It is one of the first organs to start functioning during development. Mechanisms of blood vessel formation have become a subject of high scientific and clinical interest. In adults however, it is difficult to visualize the vasculature in most living animals due to their localization deep within other tissues. Nevertheless, visualization of blood vessels remains important for several studies such as endocrinology and neurobiology. While several transgenic lines have been developed in zebrafish, with blood vessels directly visualized through expression of fluorescent proteins, no such tools exist for other teleost species. Using medaka (Oryzias latipes) as a model, the current protocol presents a quick and direct technique to label blood vessels in brain and pituitary by perfusing through the heart with fixative containing DiI. This protocol allows improvement of our understanding on how brain and pituitary cells interact with blood vasculature in whole tissue or thick tissue slices.

• Raheel, Tayyaba Qureshi; Sørensen, Christina; Berghuis, Paul; Jensen, Vidar; Dobszay, Marton B. & Farkas, Tamás [Show all 14 contributors for this article] (2019). The glutamine transporter Slc38a1 regulates GABAergic neurotransmission and synaptic plasticity. Cerebral Cortex. ISSN 1047-3211. 29(12), p. 5166–5179. doi: 10.1093/cercor/bhz055. Full text in Research Archive
• Burow, Susann; Fontaine, Romain; von Krogh, Kristine; Mayer, Ian; Nourizadeh-Lillabadi, Rasoul & Hollander-Cohen, Lian [Show all 10 contributors for this article] (2019). Data on Western blot and ELISA analysis of medaka (Oryzias latipes) follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) using recombinant proteins expressed with Pichia pastoris. Data in Brief. ISSN 2352-3409. 22, p. 1057–1063. doi: 10.1016/j.dib.2019.01.034. Full text in Research Archive
• Mäki-Marttunen, Tuomo; Kaufmann, Tobias; Elvsåshagen, Torbjørn; Devor, Anna; Djurovic, Srdjan & Westlye, Lars Tjelta [Show all 23 contributors for this article] (2019). Biophysical Psychiatry—How Computational Neuroscience Can Help to Understand the Complex Mechanisms of Mental Disorders. Frontiers in Psychiatry. ISSN 1664-0640. 10. doi: 10.3389/fpsyt.2019.00534. Full text in Research Archive
• O`Connell, Kevin; Shadrin, Alexey A.; Smeland, Olav Bjerkehagen; Bahrami, Shahram; Frei, Oleksandr & Bettella, Francesco [Show all 24 contributors for this article] (2019). Identification of genetic loci shared between ADHD, intelligence and educational attainment . Biological Psychiatry. ISSN 0006-3223. 87(12), p. 1052–1062. doi: 10.1016/j.biopsych.2019.11.015. Full text in Research Archive
• Burow, Susann; Fontaine, Romain; von Krogh, Kristine; Mayer, Ian; Nourizadeh-Lillabadi, Rasoul & Hollander-Cohen, Lian [Show all 10 contributors for this article] (2019). Medaka Follicle-stimulating hormone (Fsh) and Luteinizing hormone (Lh): Developmental profiles of pituitary protein and gene expression levels. General and Comparative Endocrinology. ISSN 0016-6480. 272, p. 93–108. doi: 10.1016/j.ygcen.2018.12.006. Show summary

  The two gonadotropins follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) are of particular importance within the hypothalamic-pituitary-gonadal (HPG) axis of vertebrates. In the current study, we demonstrate the production and validation of Japanese medaka (Oryzias latipes) recombinant (md) gonadotropins Fshβ (mdFshβ), Lhβ (mdLhβ), Fshβα (mdFshβα), and Lhβα (mdLhβα) by Pichia pastoris, the generation of specific rabbit antibodies against their respective β subunits, and their use within the development and validation of competitive enzyme-linked immunosorbent assays (ELISAs) for quantification of medaka Fsh and Lh. mdFsh and mdLh were produced as single-chain polypeptides by linking the α subunit with mdFshβ or mdLhβ mature protein coding sequences to produce a “tethered” polypeptide with the β-chain at the N-terminal and the α-chain at the C-terminal. The specificity of the antibodies raised against mdFshβ and mdLhβ was determined by immunofluorescence (IF) for Fshβ and Lhβ on medaka pituitary tissue, while comparison with fluorescence in situ hybridization (FISH) for fshb and lhb mRNA was used for validation. Competitive ELISAs were developed using antibodies against mdFshβ or mdLhβ, and the tethered proteins mdFshβα or mdLhβα for standard curves. The standard curve for the Fsh ELISA ranged from 97.6 pg/ml to 50 ng/ml, and for the Lh ELISA from 12.21 pg/ml to 6.25 ng/ml. The sensitivity of the assays for Fsh and Lh was 44.7 and 70.8 pg/ml, respectively. A profile of pituitary protein levels of medaka Fsh and Lh comparing juveniles with adults showed significant increase of protein amount from juvenile group (body length from 12 mm to 16.5 mm) to adult group (body length from 21 mm to 26.5 mm) for both hormones in male medaka. Comparing these data to a developmental profile of pituitary mRNA expression of medaka fshb and lhb, the mRNA expression of lhb also increased during male maturation and a linear regression analysis revealed a significant increase of lhb expression with increased body length that proposes a linear model. However, fshb mRNA expression did not change significantly during male development and therefore was not correlated with body length. In summary, we have developed and validated homologous ELISA assays for medaka Fsh and Lh based on proteins produced in P. pastoris, assays that will be used to study the functions and regulations of Fsh and Lh in more detail.

• Fontaine, Romain David; Ciani, Elia; Haug, Trude M; Hodne, Kjetil; Ager-Wick, Eirill & Baker, Dianne [Show all 7 contributors for this article] (2019). Gonadotrope plasticity at cellular, population and structural levels: A comparison between fishes and mammals. General and Comparative Endocrinology. ISSN 0016-6480. 287, p. 1–20. doi: 10.1016/j.ygcen.2019.113344. Full text in Research Archive Show summary

  Often referred to as “the master gland”, the pituitary is a key organ controlling growth, maturation, and homeostasis in vertebrates. The anterior pituitary, which contains several hormone-producing cell types, is highly plastic and thereby able to adjust the production of the hormones governing these key physiological processes according to the changing needs over the life of the animal. Hypothalamic neuroendocrine control and feedback from peripheral tissues modulate pituitary cell activity, adjusting levels of hormone production and release according to different functional or environmental requirements. However, in some physiological processes (e.g. growth, puberty, or metamorphosis), changes in cell activity may be not sufficient to meet the needs and a general reorganization of cell composition and pituitary structure may occur. Focusing on gonadotropes, this review examines plasticity at the cellular level, which allows precise and rapid control of hormone production and secretion, as well as plasticity at the population and structural levels, which allows more substantial changes in hormone production. Further, we compare current knowledge of the anterior pituitary plasticity in fishes and mammals in order to assess what has been conserved or not throughout evolution, and highlight important remaining questions.

• Halnes, Geir; Tennøe, Simen; Haug, Trude; Einevoll, Gaute; Weltzien, Finn-Arne & Hodne, Kjetil (2019). A computational model for gonadotropin releasing cells in the teleost fish medaka. PLoS Computational Biology. ISSN 1553-734X. 15(8), p. 1–28. doi: 10.1371/journal.pcbi.1006662. Full text in Research Archive Show summary

  Pituitary endocrine cells fire action potentials (APs) to regulate their cytosolic Ca2+ concentration and hormone secretion rate. Depending on animal species, cell type, and biological conditions, pituitary APs are generated either by TTX-sensitive Na+ currents (INa), high-voltage activated Ca2+ currents (ICa), or by a combination of the two. Previous computational models of pituitary cells have mainly been based on data from rats, where INa is largely inactivated at the resting potential, and spontaneous APs are predominantly mediated by ICa. Unlike in rats, spontaneous INa-mediated APs are consistently seen in pituitary cells of several other animal species, including several species of fish. In the current work we develop a computational model of gonadotropin releasing cells in the teleost fish medaka (Oryzias latipes). The model stands out from previous modeling efforts by being (1) the first model of a pituitary cell in teleosts, (2) the first pituitary cell model that fires sponateous APs that are predominantly mediated by INa, and (3) the first pituitary cell model where the kinetics of the depolarizing currents, INa and ICa, are directly fitted to voltage-clamp data. We explore the firing properties of the model, and compare it to the properties of previous models that fire ICa-based APs. We put a particular focus on how the big conductance K+ current (IBK) modulates the AP shape. Interestingly, we find that IBK can prolong AP duration in models that fire ICa-based APs, while it consistently shortens the duration of the predominantly INa-mediated APs in the medaka gonadotroph model. Although the model is constrained to experimental data from gonadotroph cells in medaka, it may likely provide insights also into other pituitary cell types that fire INa-mediated APs.

• Rødevand, Linn ; Steen, Nils Eiel; Elvsåshagen, Torbjørn; Quintana, Daniel; Reponen, Elina Johanna & Mørch, Ragni Helene [Show all 12 contributors for this article] (2019). Cardiovascular risk remains high in schizophrenia with modest improvements in bipolar disorder during past decade. Acta Psychiatrica Scandinavica. ISSN 0001-690X. 139(4), p. 348–360. doi: 10.1111/acps.13008. Show summary

  Objective: While CVD risk has decreased in the general population during the last decade, the situation in patients with schizophrenia (SCZ) and bipolar disorder (BD) is unknown. Methods: We compared CVD risk factors in patients with SCZ and BD recruited from 2002‐2005 (2005 sample, N = 270) with patients recruited from 2006‐2017 (2017 sample, N = 1011) from the same catchment area in Norway. The 2017 sample was also compared with healthy controls (N = 922) and the general population (N range = 1285‐4587, Statistics Norway) from the same area and period. Results: Patients with SCZ and BD in the 2017 sample had significantly higher level of most CVD risk factors compared to healthy controls and the general population. There was no significant difference in the prevalence of CVD risk factors in SCZ between the 2005 and 2017 samples except a small increase in glucose in the 2017 sample. There were small‐to‐moderate reductions in hypertension, obesity, total cholesterol, low‐density lipoprotein, systolic and diastolic blood pressure in the BD 2017 sample compared to the 2005 sample. Conclusion: Despite major advances in health promotion during the past decade, there has been no reduction in the level of CVD risk factors in patients with SCZ and modest improvement in BD.

• Buccino, Alessio Paolo; Kordovan, Michael; Ness, Torbjørn V; Merkt, Benjamin; Häfliger, Philipp & Fyhn, Marianne [Show all 9 contributors for this article] (2018). Combining biophysical modeling and deep learning for multielectrode array neuron localization and classification. Journal of Neurophysiology. ISSN 0022-3077. 120(3), p. 1212–1232. doi: 10.1152/jn.00210.2018. Full text in Research Archive
• Fontaine, Romain; Hodne, Kjetil & Weltzien, Finn-Arne (2018). Healthy Brain-pituitary Slices for Electrophysiological Investigations of Pituitary Cells in Teleost Fish. Journal of Visualized Experiments. ISSN 1940-087X. 2018(138). doi: 10.3791/57790. Full text in Research Archive Show summary

  Electrophysiological investigations of pituitary cells have been conducted in numerous vertebrate species, but very few in teleost fish. Among these, the clear majority have been performed on dissociated primary cells. To improve our understanding of how teleost pituitary cells, behave in a more biologically relevant environment, this protocol shows how to prepare viable brain-pituitary slices using the small freshwater fish medaka (Oryzias latipes). Making the brain-pituitary slices, pH and osmolality of all solutions were adjusted to values found in body fluids of freshwater fish living at 25 to 28 °C. Following slice preparation, the protocol demonstrates how to conduct electrophysiological recordings using the perforated whole-cell patch-clamp technique. The patch-clamp technique is a powerful tool with unprecedented temporal resolution and sensitivity, allowing investigation of electrical properties from intact whole cells down to single ion channels. Perforated patch is unique in that it keeps the intracellular environment intact preventing regulatory elements in the cytosol from being diluted by the patch pipette electrode solution. In contrast, when performing traditional whole-cell recordings, it was observed that medaka pituitary cells quickly lose their ability to fire action potentials. Among the various perforation techniques available, this protocol demonstrates how to achieve perforation of the patched membrane using the fungicide Amphotericin B.

• Mäki-Marttunen, Tuomo; Halnes, Geir; Devor, Anna; Metzner, Christoph; Dale, Anders M. & Andreassen, Ole Andreas [Show all 7 contributors for this article] (2018). A stepwise neuron model fitting procedure designed for recordings with high spatial resolution: Application to layer 5 pyramidal cells. Journal of Neuroscience Methods. ISSN 0165-0270. 293, p. 264–283. doi: 10.1016/j.jneumeth.2017.10.007. Full text in Research Archive
• Martínez-Cañada, Pablo; Mobarhan, Milad; Halnes, Geir; Fyhn, Marianne; Morillas, Christian & Pelayo, Francisco [Show all 7 contributors for this article] (2018). Biophysical network modeling of the dLGN circuit: Effects of cortical feedback on spatial response properties of relay cells. PLoS Computational Biology. ISSN 1553-734X. 14(1), p. 1–45. doi: 10.1371/journal.pcbi.1005930. Full text in Research Archive
• Dragly, Svenn-Arne; Mobarhan, Milad; Lepperød, Mikkel Elle; Tennøe, Simen; Fyhn, Marianne & Hafting, Torkel [Show all 7 contributors for this article] (2018). Experimental directory structure (Exdir): An alternative to HDF5 without introducing a new file format. Frontiers in Neuroinformatics. ISSN 1662-5196. 12. doi: 10.3389/fninf.2018.00016.
• Buccino, Alessio Paolo; Lepperød, Mikkel Elle; Dragly, Svenn-Arne; Häfliger, Philipp; Fyhn, Marianne & Hafting, Torkel (2018). Open source modules for tracking animal behavior and closed-loop stimulation based on Open Ephys and Bonsai. Journal of Neural Engineering. ISSN 1741-2560. 15, p. 1–12. doi: 10.1088/1741-2552/aacf45. Full text in Research Archive
• Gratiy, Sergey L.; Halnes, Geir; Denman, Daniel; Hawrylycz, Michael J; Koch, Christof & Einevoll, Gaute [Show all 7 contributors for this article] (2017). From Maxwell's equations to the theory of current-source density analysis. European Journal of Neuroscience. ISSN 0953-816X. 45(8), p. 1013–1023. doi: 10.1111/ejn.13534. Full text in Research Archive
• Halnes, Geir; Mäki-Marttunen, Tuomo; Pettersen, Klas; Andreassen, Ole Andreas & Einevoll, Gaute (2017). Ion diffusion may introduce spurious current sources in current-source density (CSD) analysis. Journal of Neurophysiology. ISSN 0022-3077. 118(1), p. 114–120. doi: 10.1152/jn.00976.2016. Full text in Research Archive
• Tveito, Aslak; Jæger, Karoline Horgmo; Lines, Glenn Terje; Paszkowski, Lukasz; Sundnes, Joakim & Edwards, Andrew [Show all 9 contributors for this article] (2017). An evaluation of the accuracy of classical models for computing the membrane potential and extracellular potential for neurons. Frontiers in Computational Neuroscience. ISSN 1662-5188. 11. doi: 10.3389/fncom.2017.00027. Full text in Research Archive

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• Ness, Torbjørn V; Halnes, Geir; Næss, Solveig; Pettersen, Klas Henning & Einevoll, Gaute (2022). Computing Extracellular Electric Potentials from Neuronal Simulations. In Negrello, M (Eds.), Computational Modelling of the Brain.. Springer. ISSN 978-3-030-89439-9. p. 179–199. doi: 10.1007/978-3-030-89439-9_8.
• Sætra, Marte Julie; Einevoll, Gaute T. & Halnes, Geir (2019). A two-compartment neuron model with ion conservation and ion pumps.
• Fyhn, Marianne & Einevoll, Gaute (2019). Hjernen digitaliseres - hvordan moderne datateknologi brukes til å forstå biologiske mekanismer i hjernen.
• Hagen, Espen; Stasik, Alexander Johannes; Billeh, Yazan N.; Siegle, Joshua H.; Dai, Kael & Rimehaug, Atle Eskeland [Show all 14 contributors for this article] (2019). Comparing spikes and the local field potential (LFP) in V1 between experimental data and a comprehensive biophysical model.
• Mäki-Marttunen, Tuomo (2018). Lecture series on modelling of neuronal electrophysiology.
• Mäki-Marttunen, Tuomo; Edwards, Andrew G & Blackwell, Kim T (2018). Construction of a biochemically detailed single-compartment model for post-synaptic long-term potentiation: application to cortical plasticity.
• Mäki-Marttunen, Tuomo; Blackwell, Kim T & Edwards, Andrew G (2018). Unified biochemical model for long-term synaptic plasticity in the cortex – what are the essential pathways?
• Hazen, Jennifer; Wigestrand, Mattis B; Aasebø, Ida Elisabeth Jørgensen; Tully, Annabelle; Dinh, Tovy & Lepperød, Mikkel [Show all 8 contributors for this article] (2018). Lateral hypothalamic area projection neurons contribute to an innate freezing response.
• Grødem, Sverre; Sandvik, Guro Katrine; Hazen, Jennifer; Lensjø, Kristian Kinden; Hafting, Torkel & Fyhn, Marianne (2018). A CRISPR-Cas9 platform for genetic perturbations of brain extracellular matrix regulators in vivo .
• Halnes, Geir (2018). An electrodiffusive framework for large scale ion concentration dynamics in neural tissue. .
• Sætra, Marte Julie (2017). Hva har krefter med hjernen vår å gjøre? Titan.uio.no.
• Sætra, Marte Julie (2017). Kan databeregninger erstatte dyreforsøk? Aftenposten (morgenutg. : trykt utg.). ISSN 0804-3116.
• Sætra, Marte Julie (2017). Can Computer Simulations Substitute Animal Research? digitallifenorway.org.
• Sætra, Marte Julie; Dale, Anders M.; Devor, Anna & Einevoll, Gaute T. (2017). Estimation of Oxygen Consumption From Optical Measurements in Cortex.
• Næss, Solveig; Ness, Torbjørn V; Halnes, Geir; Halgren, Eric; Dale, Anders M. & Einevoll, Gaute (2017). Biophysical modeling of single-neuron contributions to ECoG and EEG signals.
• Næss, Solveig; Ness, Torbjørn V; Halnes, Geir; Halgren, Eric; Dale, Anders M. & Einevoll, Gaute (2017). Biophysical modeling of single neuron contributions to ECoG and EEG signals.
• Halnes, Geir (2017). Hjerneforskning.
• Halnes, Geir; Mäki-Marttunen, Tuomo; Pettersen, Klas; Andreassen, Ole Andreas & Einevoll, Gaute T. (2017). Extracellular diffusion can introduce errors in current source density estimates.
• Mobarhan, Milad; Halnes, Geir; Martínez-Cañada, Pablo; Hafting, Torkel; Fyhn, Marianne & Einevoll, Gaute (2017). Firing-rate Based Network Modeling of the dLGN Circuit: Effects of Cortical Feedback on Spatiotemporal Response Properties of Relay Cells .
• Halnes, Geir (2017). An electrodiffusive formalism for ion concentration dynamics and liquid flow in brain tissue.
• Halnes, Geir; Solbrå, Andreas Våvang; Mäki-Marttunen, Tuomo; Pettersen, Klas; Andreassen, Ole Andreas & Malthe-Sørensen, Anders [Show all 7 contributors for this article] (2017). Modelling electrical and chemical dynamics in brain tissue.
• Sætra, Marte Julie; Dale, Anders M.; Devor, Anna & Einevoll, Gaute T. (2017). Estimation of Oxygen Consumption From Optical Measurements in Cortex.
• Sætra, Marte Julie; Dale, Anders M.; Devor, Anna & Einevoll, Gaute T. (2017). Estimation of Oxygen Consumption From Optical Measurements in Cortex.
• Næss, Solveig; Ness, Torbjørn V; Halnes, Geir; Halgren, Eric; Dale, Anders & Einevoll, Gaute (2017). Biophysical modeling of single-neuron contributions toECoG, EEG and MEG signals.
• Sætra, Marte Julie (2017). Foredrag om hjernefysikk.

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