Johan Frederik Storm

• Arena, Alessandro; Thon, Sarah; Casali, Adenauer Girardi & Storm, Johan Frederik (2020). General anaesthesia disrupts complex cortical dynamics in response to intracranial electrical stimulation in rats. BioRxiv.  ISSN 0362-4331. . doi: 10.1101/2020.02.25.964056
• Aru, Jaan; Phillips, William A & Storm, Johan Frederik (2020). Apical drive - a cellular mechanism of dreaming?. Neuroscience and Biobehavioral Reviews.  ISSN 0149-7634.  119, s 450- 455 . doi: 10.1016/j.neubiorev.2020.09.018
• Farnes, Nadine; Juel, Bjørn Erik; Nilsen, Andre Sevenius; Romundstad, Luis Georg & Storm, Johan Frederik (2020). Increased signal diversity/complexity of spontaneous EEG in humans given sub-anaesthetic doses of ketamine. PLOS ONE.  ISSN 1932-6203. Show summary

  Objective How and to what extent electrical brain activity is affected in pharmacologically altered states of consciousness, where it is mainly the phenomenological content rather than the level of consciousness that is altered, is not well understood. An example is the moderately psychedelic state caused by low doses of ketamine. Therefore, we investigated whether and how measures of evoked and spontaneous electroencephalographic (EEG) signal diversity are altered by sub-anaesthetic levels of ketamine compared to normal wakefulness, and how these measures relate to subjective assessments of consciousness. Methods High-density electroencephalography (EEG, 62 channels) was used to record spontaneous brain activity and responses evoked by transcranial magnetic stimulation (TMS) in 10 healthy volunteers before and after administration of sub-anaesthetic doses of ketamine in an open-label within-subject design. Evoked signal diversity was assessed using the perturbational complexity index (PCI), calculated from the global EEG responses to local TMS perturbations. Signal diversity of spontaneous EEG, with eyes open and eyes closed, was assessed by Lempel Ziv complexity (LZc), amplitude coalition entropy (ACE), and synchrony coalition entropy (SCE). Results Although no significant difference was found in the index of TMS-evoked complexity (PCI) between the sub-anaesthetic ketamine condition and normal wakefulness, all the three measures of spontaneous EEG signal diversity showed significantly increased values in the sub-anaesthetic ketamine condition. This increase in signal diversity also correlated with subjective assessment of altered states of consciousness. Moreover, spontaneous signal diversity was significantly higher when participants had eyes open compared to eyes closed, both during normal wakefulness and during influence of sub-anaesthetic ketamine doses. Conclusion The results suggest that PCI and spontaneous signal diversity may be complementary and potentially measure different aspects of consciousness. Thus, our results seem compatible with PCI being indicative of the brain’s ability to sustain consciousness, as indicated by previous research, while it is possible that spontaneous EEG signal diversity may be indicative of the complexity of conscious content. The observed sensitivity of the latter measures to visual input seems to support such an interpretation. Thus, sub-anaesthetic ketamine may increase the complexity of both the conscious content (experience) and the brain activity underlying it, while the level, degree, or general capacity of consciousness remains largely unaffected.

• Halder, Sebastian; Juel, Bjørn Erik; Nilsen, Andre Sevenius; Raghavan, L Venkat & Storm, Johan Frederik (2020). Changes in measures of consciousness during anaesthesia of one hemisphere (Wada test). NeuroImage.  ISSN 1053-8119. . doi: https://doi.org/10.1016/j.neuroimage.2020.117566
• Juel, Bjørn Erik; Romundstad, Luis Georg; Storm, Johan Frederik & Larsson, Pål Gunnar (2020). Validation of a new approach for distinguishing anesthetized from awake state in patients using Directed Transfer Function applied to raw EEG. (In press). Journal of clinical monitoring and computing.  ISSN 1387-1307. . doi: 10.1101/2020.06.18.20131508
• Juel, Bjørn Erik; Romundstad, Luis Georg; Storm, Johan Frederik & Larsson, Pål Gunnar (2020). Validation of a new approach for distinguishing anesthetized from awake state in patients using directed transfer function applied to raw EEG. Journal of clinical monitoring and computing.  ISSN 1387-1307.  s 1- 14 . doi: 10.1007/s10877-020-00603-x
• Nilsen, Andre Sevenius; Juel, Bjørn Erik; Farnes, Nadine; Romundstad, Luis Georg & Storm, Johan Frederik (2020). Behavioral effects of sub-anesthetic ketamine in a go/no-go task. Journal of Psychedelic Studies.  ISSN 2559-9283. . doi: https://doi.org/10.1556/2054.2020.00126 Full text in Research Archive.
• Nilsen, Andre Sevenius; Juel, Bjørn Erik; Thürer, Benjamin & Storm, Johan Frederik (2020). Proposed EEG measures of consciousness: asystematic, comparative review. PsyArXiv. . doi: 10.31234/osf.io/sjm4a
• Storm, Johan Frederik (2020). Why Does the Brain-Mind (Consciousness) Problem Seem So Hard? Reflections on Our Mental Limitations and Dualistic Intuitions: Neuroscepticism/Neuro-complementarity. Journal of Consciousness Studies.  ISSN 1355-8250.  27(5-6), s 174- 189
• Hagger-Vaughan, Nicholas & Storm, Johan Frederik (2019). Synergy of Glutamatergic and Cholinergic Modulation Induces Plateau Potentials in Hippocampal OLM Interneurons. Frontiers in Cellular Neuroscience.  ISSN 1662-5102.  13 . doi: 10.3389/fncel.2019.00508 Full text in Research Archive. Show summary

  Oriens-lacunosum moleculare (OLM) cells are hippocampal inhibitory interneurons that are implicated in the regulation of information flow in the CA1 circuit, inhibiting cortical inputs to distal pyramidal cell dendrites, whilst disinhibiting CA3 inputs to pyramidal cells. OLM cells express metabotropic cholinergic (mAChR) and glutamatergic (mGluR) receptors, so modulation of these cells via these receptors may contribute to switching between functional modes of the hippocampus. Using a transgenic mouse line to identify OLM cells, we found that both mAChR and mGluR activation caused the cells to exhibit long-lasting depolarizing plateau potentials following evoked spike trains. Both mAChR- and mGluR-induced plateau potentials were eliminated by blocking transient receptor potential (TRP) channels, and were dependent on intracellular calcium concentration and calcium entry. Pharmacological tests indicated that Group I mGluRs are responsible for the glutamatergic induction of plateaus. There was also a pronounced synergy between the cholinergic and glutamatergic modulation, plateau potentials being generated by agonists applied together at concentrations too low to elicit any change when applied individually. This synergy could enable OLM cells to function as coincidence detectors of different neuromodulatory systems, leading to their enhanced and prolonged activation and a functional change in information flow within the hippocampus.

• Kusztor, Aniko; Raud, Liisa; Juel, Bjørn Erik; Nilsen, Andre Sevenius; Storm, Johan Frederik & Huster, Rene (2019). Sleep deprivation differentially affects subcomponents of cognitive control. Sleep.  ISSN 0161-8105.  42(4) . doi: 10.1093/sleep/zsz016
• Juel, Bjørn Erik; Romundstad, Luis Georg; Kolstad, Frode; Storm, Johan Frederik & Larsson, Pål Gunnar (2018). Distinguishing anesthetized from awake state in patients: A new approach using one second segments of raw EEG. Frontiers in Human Neuroscience.  ISSN 1662-5161.  12:40, s 1- 14 . doi: 10.3389/fnhum.2018.00040 Full text in Research Archive.
• Phillips, William A; Bachmann, Talis & Storm, Johan Frederik (2018). Apical Function in Neocortical Pyramidal Cells: A Common Pathway by Which General Anesthetics Can Affect Mental State. Frontiers in Neural Circuits.  ISSN 1662-5110.  12, s 1- 15 . doi: 10.3389/fncir.2018.00050 Full text in Research Archive.
• Hönigsperger, Christoph; Nigro, Maximiliano José & Storm, Johan Frederik (2017). Physiological roles of Kv2 channels in entorhinal cortex layer II stellate cells revealed by Guangxitoxin-1E. Journal of Physiology.  ISSN 0022-3751.  595(3), s 739- 757 . doi: 10.1113/JP273024 Full text in Research Archive.
• Storm, Johan Frederik; Boly, Melanie; Casali, Adenauer G.; Massimini, Marcello; Olcese, Umberto; Pennartz, Cyriel M.A. & Wilke, Melanie (2017). Consciousness regained: Disentangling mechanisms, brain systems, and behavioral responses. Journal of Neuroscience.  ISSN 0270-6474.  37(45), s 10882- 10893 . doi: 10.1523/JNEUROSCI.1838-17.2017 Full text in Research Archive.
• Hönigsperger, Christoph; Marosi, Mate Gabor; Murphy, Ricardo & Storm, Johan Frederik (2015). Dorsoventral differences in Kv7/M-current and its impact on resonance, temporal summation and excitability in rat hippocampal pyramidal cells. Journal of Physiology.  ISSN 0022-3751.  593(7), s 1551- 1580 . doi: 10.1113/jphysiol.2014.280826
• Wang, Kang; Mateos-Aparicio, Pedro; Hönigsperger, Christoph; Raghuram, Vijeta; Wu, Wendy W.; Ridder, Margreet C.; Sah, Pankaj; Maylie, James; Storm, Johan Frederik & Adelman, John P. (2015). IK1 Channels Do Not Contribute to the Slow Afterhyperpolarization in Pyramidal Neurons. eLIFE.  ISSN 2050-084X. . doi: 10.1093/toxsci/kfv245
• Nigro, Maximiliano José; Mateos-Aparicio, Pedro & Storm, Johan Frederik (2014). Expression and functional roles of Kv7/KCNQ/M-channels in rat medial entorhinal cortex layer II stellate cells. Journal of Neuroscience.  ISSN 0270-6474.  34(20), s 6807- 6812 . doi: 10.1523/JNEUROSCI.4153-13.2014
• Giglio, Anna Maria & Storm, Johan Frederik (2014). Postnatal development of temporal integration, spike timing and spike threshold regulation by a dendrotoxin-sensitive K+ current in rat CA1 hippocampal cells. European Journal of Neuroscience.  ISSN 0953-816X.  39(1), s 12- 23 . doi: 10.1111/ejn.12385 Show summary

  Spike timing and network synchronization are important for plasticity, development and maturation of brain circuits. Spike delays and timing can be strongly modulated by a low-threshold, slowly inactivating, voltage-gated potassium current called D-current (ID ). ID can delay the onset of spiking, cause temporal integration of multiple inputs, and regulate spike threshold and network synchrony. Recent data indicate that ID can also undergo activity-dependent, homeostatic regulation. Therefore, we have studied the postnatal development of ID -dependent mechanisms in CA1 pyramidal cells in hippocampal slices from young rats (P7-27), using somatic whole-cell recordings. At P21-27, these neurons showed long spike delays and pronounced temporal integration in response to a series of brief depolarizing current pulses or a single long pulse, whereas younger cells (P7-20) showed shorter discharge delays and weak temporal integration, although the spike threshold became increasingly negative with maturation. Application of α-dendrotoxin (α-DTX), which blocks ID , reduced the spiking latency and temporal integration most strongly in mature cells, while shifting the spike threshold most strongly in a depolarizing direction in these cells. Voltage-clamp analysis revealed an α-DTX-sensitive outward current (ID ) that increased in amplitude during development. In contrast to P21-23, ID in the youngest group (P7-9) showed smaller peri-threshold amplitude. This may explain why long discharge delays and robust temporal integration only appear later, 3 weeks postnatally. We conclude that ID properties and ID -dependent functions develop postnatally in rat CA1 pyramidal cells, and ID may modulate network activity and plasticity through its effects on synaptic integration, spike threshold, timing and synchrony

• Mateos-Aparicio, Pedro; Murphy, Ricardo & Storm, Johan Frederik (2014). Complementary functions of SK and Kv7/M potassium channels in excitability control and synaptic integration in rat hippocampal dentate granule cells. Journal of Physiology.  ISSN 0022-3751.  592(4), s 669- 693 . doi: 10.1113/jphysiol.2013.267872
• Molden, Sturla; Moldestad, Olve & Storm, Johan Frederik (2013). Estimating Extracellular Spike Waveforms from CA1 Pyramidal Cells with Multichannel Electrodes. PLOS ONE.  ISSN 1932-6203.  8(12) . doi: 10.1371/journal.pone.0082141
• Lauritzen, Knut Husø; Dalhus, Bjørn; Storm, Johan Frederik; Bjørås, Magnar & Klungland, Arne (2011). Modeling the impact of mitochondrial DNA damage in forebrain neurons and beyond. Mechanisms of Ageing and Development.  ISSN 0047-6374.  132(8-9), s 424- 428 . doi: 10.1016/j.mad.2011.02.006
• Kaufmann, Walter A.; Kasugai, Y; Ferraguti, F & Storm, Johan Frederik (2010). TWO DISTINCT POOLS OF LARGE-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS IN THE SOMATIC PLASMA MEMBRANE OF CENTRAL PRINCIPAL NEURONS. Neuroscience.  ISSN 0306-4522.  169(3), s 974- 986 . doi: 10.1016/j.neuroscience.2010.05.070
• Lauritzen, Knut Husø; Moldestad, Olve; Eide, Lars; Carlsen, Harald; Nesse, Gaute; Storm, Johan Frederik; Mansuy, Isabelle M.; Bergersen, Linda Hildegard & Klungland, Arne (2010). Mitochondrial DNA Toxicity in Forebrain Neurons Causes Apoptosis, Neurodegeneration, and Impaired Behavior. Molecular and Cellular Biology.  ISSN 0270-7306.  30(6), s 1357- 1367 . doi: 10.1128/MCB.01149-09 Show summary

  Mitochondrial dysfunction underlying changes in neurodegenerative diseases is often associated with apoptosis and a progressive loss of neurons, and damage to the mitochondrial genome is proposed to be involved in such pathologies. In the present study we designed a mouse model that allows us to specifically induce mitochondrial DNA toxicity in the forebrain neurons of adult mice. This is achieved by CaMKII-regulated inducible expression of a mutated version of the mitochondrial UNG DNA repair enzyme (mutUNG1). This enzyme is capable of removing thymine from the mitochondrial genome. We demonstrate that a continual generation of apyrimidinic sites causes apoptosis and neuronal death. These defects are associated with behavioral alterations characterized by increased locomotor activity, impaired cognitive abilities, and lack of anxietylike responses. In summary, whereas mitochondrial base substitution and deletions previously have been shown to correlate with premature and natural aging, respectively, we show that a high level of apyrimidinic sites lead to mitochondrial DNA cytotoxicity, which causes apoptosis, followed by neurodegeneration.

• Liao, Yiliu; Kristiansen, Åse-Marit; Oksvold, Cecilie Petterson; Tuvnes, Frode Alexander; Gu, Ning; Rundén-Pran, Elise; Ruth, Peter; Sausbier, Matthias & Storm, Johan Frederik (2010). Neuronal Ca2+-Activated K+ Channels Limit Brain Infarction and Promote Survival. PLOS ONE.  ISSN 1932-6203.  5(12) . doi: 10.1371/journal.pone.0015601 Full text in Research Archive.
• Hu, Hua; Vervaeke, Koen; Graham, Lyle & Storm, Johan Frederik (2009). Complementary Theta Resonance Filtering by Two Spatially Segregated Mechanisms in CA1 Hippocampal Pyramidal Neurons. Journal of Neuroscience.  ISSN 0270-6474.  29(46), s 14472- 14483 . doi: 10.1523/JNEUROSCI.0187-09.2009
• Kaufmann, Walter A.; Ferraguti, Francesco; Fukazawa, Yugo; Kasugai, Yu; Shigemoto, Ryuichi; Laake, Petter; Sexton, Joseph A.; Ruth, Peter; Wietzorrek, Georg; Knaus, Hans Gunther; Storm, Johan Frederik & Ottersen, Ole Petter (2009). Large-Conductance Calcium-Activated Potassium Channels in Purkinje Cell Plasma Membranes Are Clustered at Sites of Hypolemmal Microdomains. Journal of Comparative Neurology.  ISSN 0021-9967.  515(2), s 215- 230 . doi: 10.1002/cne.22066
• Moldestad, Olve; Karlsen, Pernille; Molden, Sturla & Storm, Johan Frederik (2009). Tracheotomy improves experiment success rate in mice during urethane anesthesia and stereotaxic surgery. Journal of Neuroscience Methods.  ISSN 0165-0270.  176(2), s 57- 62 . doi: 10.1016/j.jneumeth.2008.08.015
• Storm, Johan Frederik; Vervaeke, Koen Gerard Alois & Hu, Hua (2009). Functions of the Persistent Na+ Current in Cortical Neurons Revealed by Dynamic Clamp, In Alain Destexhe & Thierry Bal (ed.),  Dynamic-clamp: From Principles To Applications.  Springer.  ISBN 978-0-387-89278-8.  Kapittel 8.  s 165 - 199
• Storm, Johan Frederik; Vervaeke, Koen Gerard Alois; Hu, Hua & Graham, LJ (2009). Functions of the persistent Na+ current in cortical neurons revealed by dynamic clamp, In Alain Destexhe & Thierry Bal (ed.),  Dynamic-clamp: From Principles To Applications.  Springer.  ISBN 978-0-387-89278-8.  1.  s 1 - 33
• Gu, Ning; Hu, Hua; Vervaeke, Koen Gerard Alois & Storm, Johan Frederik (2008). SK (K(Ca)2) Channels Do Not Control Somatic Excitability in CA1 Pyramidal Neurons But Can Be Activated by Dendritic Excitatory Synapses and Regulate Their Impact. Journal of Neurophysiology.  ISSN 0022-3077.  100(5), s 2589- 2604 . doi: 10.1152/jn.90433.2008
• Gu, Ning; Vervaeke, Koen Gerard Alois & Storm, Johan Frederik (2007). BK potassium channels facilitate high-frequency firing and cause early spike frequency adaptation in rat CA1 hippocampal pyramidal cells. Journal of Physiology.  ISSN 0022-3751.  580.3, s 859- 882 . doi: 10.1113/jphysiol.2006.126367
• Hu, Hua; Vervaeke, Koen Gerard Alois & Storm, Johan Frederik (2007). M-channels (Kv7/KCNQ channels) that regulate synaptic integration, excitability, and spike pattern of CA1 pyramidal cells are located in the perisomatic region. Journal of Neuroscience.  ISSN 0270-6474.  27, s 1853- 1867 . doi: 10.1523/JNEUROSCI.4463-06.2007

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• Storm, Johan Frederik; Vervaeke, Koen Gerard Alois; Hu, Hua & Graham, LJ (2009). Dynamic clamp. Springer.  ISBN 978-0-387-89278-8.  429 s.

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• Gjerstad, Leif; Jensen, Vidar; Langmoen, Iver Arne; Lømo, Terje; Moser, Edvard Ingjald; Moser, May-Britt; Storm, Johan Frederik & Storm-Mathisen, Jon (2020). Per Andersen. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  9 . doi: 10.4045/tidsskr.20.0353
• Nicoll, Roger A; Storm, Johan Frederik & Storm-Mathisen, Jon (2020). Obituary. Per Andersen 1930–2020.. Neuron.  ISSN 0896-6273.  106, s 366- 368 . doi: 10.1016/j.neuron.2020.04.016
• Storm, Johan Frederik (2020). Forskergruppen "Hjernens signaler" deltar på Forskningsdagene 2020. UiO web.
• Storm, Johan Frederik (2020). Forskningsdagene 2020 - Hjernen og Bevisstheten. UiO web.
• Nilsen, Andre Sevenius; Juel, Bjørn Erik; Marshall, William & Storm, Johan Frederik (2019). Estimating Integrated Information: How noise, sampling, and perturbations affect Phi.
• Halder, Sebastian; Venkat Raghavan, L; Juel, Bjørn Erik; Nilsen, Andre Sevenius & Storm, Johan Frederik (2018). Effects of intracarotid sodium amobarbital procedure (ISAP) on cortical complexity.
• Juel, Bjørn Erik; Nilsen, Andre Sevenius; Gosseries, Olivia; Sarasso, Simone; Larsson, Pål Gunnar; Boly, Malanie; Laureys, Steven; Massimini, marcello & Storm, Johan Frederik (2018). Measures of connectivity, complexity and signal diversity in EEG distinguish conscious from unconscious state during anesthesia.
• Juel, Bjørn Erik; Nilsen, Andre Sevenius; Murphy, Ricardo & Storm, Johan Frederik (2018). Thalamocortical model for studying the effects of neuromodulation on network properties.
• Juel, Bjørn Erik; Romundstad, Luis Georg; Kolstad, Frode; Storm, Johan Frederik & Larsson, Pål Gunnar (2018). Changes in EEG captured by Directed Transfer Function is sufficient to accurately classify the state of wakefulness in patients undergoing sevoflurane anesthesia in accordance with the clinician’s judgement.
• Murphy, Ricardo; Nilsen, Andre Sevenius; Juel, Björn E; Hill, Sean; Plesser, Hans Ekkehard; Nieus, Thierry; Massimini, Marcello & Storm, Johan Frederik (2018). Implementation of the Hill-Tononi thalamocortical network model in the neural simulator NEST.
• Nilsen, Andre Sevenius; Juel, Bjørn Erik; Marshall, William & Storm, Johan Frederik (2018). Calculating conscious capacity: approximations, analogues, and correlates of PHI.
• Nilsen, Andre Sevenius; Juel, Bjørn Erik & Storm, Johan Frederik (2018). Attentional Modulation on Measures of Conscious States.
• Nilsen, Andre Sevenius & Storm, Johan Frederik (2018). Tracking conscious states: the potential of spontaneous EEG signal complexity.
• Roth, Fabian Christoph; Storm, Johan Frederik & Hu, Hua (2018). A unique subcellular distribution of HCN channels accelerates action potential propagation in GABAergic interneuron axons.
• Arena, Alessandro & Storm, Johan Frederik (2017). TOWARD THE EXPLORATION OF COMPLEXITY IN RATS.
• Bremnes, Thomas Rene; Juel, Bjørn Erik; Sarasso, Simone; Boly, Melanie; Casarotto, Silvia; Casali, Adenauer G.; Nilsen, Andre Sevenius; Tononi, Giulio; Larsson, Pål Gunnar; Laureys, Steven; Massimini, marcello & Storm, Johan Frederik (2017). Unresponsive states with and without report of conscious experience show distinct patterns of EEG-based effective brain connectivity in humans.
• Farnes, Nadine; Juel, Bjørn Erik; Nilsen, Andre Sevenius; Romundstad, Luis Georg; Larsson, Pål Gunnar; Engstrøm, Morten & Storm, Johan Frederik (2017). Integrated information in sub-anaesthetic ketamine measured by TMS and EEG.
• Hagger-Vaughan, Nicholas; Klaus, Carolin & Storm, Johan Frederik (2017). Dual adrenergic modulation of HCN channels in hippocampal and neocortical pyramidal neurons.
• Hagger-Vaughan, Nicholas & Storm, Johan Frederik (2017). Differential basal properties and metabotropic modulation responses between OLM and Martinotti cells.
• Juel, Bjørn Erik; Bremnes, Thomas Rene; Larsson, Pål Gunnar & Storm, Johan Frederik (2017). Classifying states of (un)consciousness based on one second of raw EEG.
• Juel, Bjørn Erik; Kusztor, Aniko; Nilsen, Andre Sevenius; Farnes, Nadine; Larsson, Pål Gunnar; Romundstad, Luis Georg & Storm, Johan Frederik (2017). Changes in electrophysiological markers of consciousness in response to various anesthetics.
• Juel, Bjørn Erik; Nilsen, Andre Sevenius; Farnes, Nadine & Storm, Johan Frederik (2017). Comparing electrophysiological markers of consciousness between physiologically distinct states of wakefulness.
• Murphy, Ricardo; Nilsen, Andre Sevenius; Juel, Bjørn Erik; Plesser, Hans Ekkehard; Hill, Sean; Nieus, Thierry; Massimini, Marcello & Storm, Johan Frederik (2017). Implementation of the Hill-Tononi thalamocortical network model in the neural simulator NEST.
• Nilsen, Andre Sevenius; Arena, Alessandro; Juel, Bjørn Erik; Storm, Johan Frederik; Murphy, Ricardo; Hu, Hua & Hagger-Vaughan, Nicholas (2017). Forsknigstorget: Hvordan kan hjernen skape bevissthet.
• Nilsen, Andre Sevenius; Juel, Bjørn Erik & Storm, Johan Frederik (2017). Proxies for integrated information of microscale networks Is it possible to predict PHI?.
• Nilsen, Andre Sevenius; Juel, Bjørn Erik; Storm, Johan Frederik; Murphy, Ricardo; Plesser, Hans Ekkehard; Hill, Sean; Nieus, Thierry & marcello, massimini (2017). Implementation of the Hill-Tononi thalamocortical network model in the neural simulator NEST.
• Nilsen, Andre Sevenius; Juel, Bjørn Erik; Storm, Johan Frederik; Romundstad, Luis Georg & Larsson, Pål Gunnar (2017). Markers of consciousness before, during, and after anesthesia.
• Nilsen, Andre Sevenius; Murphy, Ricardo; Juel, Bjørn Erik; Plesser, Hans Ekkehard; Hill, Sean; Nieus, Thierry; Massimini, Marcello & Storm, Johan Frederik (2017). Simulating deep sleep and awake states in a mammalian thalamocortical model.
• Nilsen, Andre Sevenius; Storm, Johan Frederik & Juel, Bjørn Erik (2017). Attentional Modulation on Measures of Conscious States.
• Hagger-Vaughan, Nicholas & Storm, Johan Frederik (2016). CA1 OLM cells exhibit plateau potentials in response to metabotropic glutamate receptor activation.
• Juel, Bjørn Erik; Bremnes, Thomas Rene; Larsson, Pål Gunnar & Storm, Johan Frederik (2016). Comparing Potential Objective Measures of Human Consciousness: the Perturbational Complexity Index and the Directed Transfer Function.
• Juel, Bjørn Erik; Romundstad, Luis Georg; Kolstad, Frode; Storm, Johan Frederik & Larsson, Pål Gunnar (2016). Differences in effective connectivity can be used to separate conscious from unconscious states in patients undergoing general anesthesia..
• Storm, Johan Frederik; Murphy, Ricardo & Mateos-Aparicio, Pedro (2016). Kv7/M-current function in axons: high-pass filtering of plateau potentials promotes full action potentials, also during cholinergic activation.
• Juel, Bjørn Erik; Romundstad, Luis Georg; Kolstad, Frode; Storm, Johan Frederik & Larsson, Pål Gunnar (2015). Can We Monitor Consciousness in Real Time with EEG?.
• Juel, Bjørn Erik; Romundstad, Luis Georg; Kolstad, Frode; Storm, Johan Frederik & Larsson, Pål Gunnar (2015). Monitoring Brain Connectivity to Predict Patients’ Level of Awareness.
• Mateos-Aparicio, Pedro; Murphy, Ricardo & Storm, Johan Frederik (2014). Dentate granule cell: mAHP & sAHP; SK & Kv7/M channels. [www /  CD]. Show summary

  The model is based on that of Aradi & Holmes (1999; Journal of Computational Neuroscience 6, 215-235). It was used to help understand the contribution of M and SK channels to the medium afterhyperpolarization (mAHP) following one or seven spikes, as well as the contribution of M channels to the slow afterhyperpolarization (sAHP). We found that SK channels are the main determinants of the mAHP, in contrast to CA1 pyramidal cells where the mAHP is primarily caused by the opening of M channels. The model reproduced these experimental results, but we were unable to reproduce the effects of the M-channel blocker XE991 on the sAHP. It is suggested that either the XE991-sensitive component of the sAHP is not due to M channels, or that when contributing to the sAHP, these channels operate in a mode different from that associated with the mAHP.

• Hönigsperger, Christoph; Nigro, Maximiliano José & Storm, Johan Frederik (2013). Physiological roles of Kv2 channels in entorhinal cortex layer II cells revealed by Guangxitoxin-1E. Show summary

  The medial entorhinal cortex (mEC) plays a central role in memory formation and spatial navigation, and is often involved in epilepsy and dementia. In the mEC circuitry, stellate cells (SCs) of the layer II occupy a key position, as they receive inputs from association areas of the neocortex, and they are the main source of the perforant path input to the hippocampus. SCs are thought to be the neural correlate of mEC grid cells, which perform path integration and play a key role in spatial navigation. Distinctive electrophysiological properties of SCs are: prominent subthreshold resonance and membrane potential oscillations/fluctuations in the theta frequency range, spike clustering, and spike frequency adaptation. Although voltage-gated potassium (Kv) channels are known to be important for the electrophysiological characteristics of neurons, their physiological roles in mEC SCs largely remain to be determined. We focused on the roles of Kv2 channels, which are known to strongly regulate excitability and the action potential (AP) waveform in several other neuron types. The Kv2 channels are often located mainly in the soma and proximal dendrites of those neurons, and underlie the main delayed rectifier Kv current that activates and inactivates relatively slowly. Here we use a recently identified powerful blocker of Kv2 channels, Guangxitoxin-1E (GxTx) to unveil the physiological roles of Kv2 channels in mEC SCs. We found that 100 nM GxTx had no effect on the cell input resistance, as expected for a Kv2 blocker, but strongly increased the amplitude and area of the afterdepolarization (ADP) following a single AP. During steady, subthreshold depolarization that evoked oscillations and spontaneous firing in control conditions, GxTx induced bursting in 7 of the 8 cells tested. Using voltage clamp recordings in nucleated patches, we found that 100 nM GxTx blocked about 40% of the current at the end of a 400 ms voltage step from -84 mV to -14 mV, but had no significant effect on the peak current within the first 10 ms after the onset of the step. These results support the idea that GxTx acts mainly on Kv2 channels. Our results support the notion that GxTx is a potent and specific blocker of Kv2 channels in EC SCs, and indicate that Kv2 channels strongly modulate the excitability, spike afterpotentials, and discharge pattern of this cell type.

• Mateos-Aparicio, Pedro & Storm, Johan Frederik (2013). Dorsoventral differences in neuromodulation of dentate gyrus granule cells.
• Mateos-Aparicio, Pedro & Storm, Johan Frederik (2013). Dorsoventral differences in neuromodulation of dentate gyrus granule cells.
• Storm, Johan Frederik (2013). Er bevissthetsproblemet et naturvitenskapelig forskbart problem?.
• Storm, Johan Frederik & Chalmers, David (2013). En samtale med David Chalmers om bevissthet og hjerne. Show summary

  På dette møtet fikk vi besøk av den berømte australske filosofen David Chalmers - en av vår tids mest markante bevissthetsfilosofer. Chalmers er en av de mest dyptpløyende deltakerne i dagens filosofiske diskusjon om bevissthetens natur. Han er kjent for sin formulering av "The hard problem of consciousness", som selve kjernespørsmålet: Hvorfor er vår hjernevirksomhet ledsaget at bevisste opplevelser, altså subjektive fornemmelser, følelser og tanker? "The easy problems of consciousness", derimot, definerer han som alle spørsmålene om hjernens målbare funksjoner som hjerneforskerne kan studere med sine metoder. Chalmers har markert seg som en skarp kritiker av den dominerende retningen i vår tids bevissthetsfilosofi: Fysikalismen – altså ideen at alt er noe fysisk, inkludert bevisstheten. Han mener fysikalismen er ute av stand til å besvare hvorfor vi har bevisste opplevelser. I motsetning til de aller fleste andre av dagens filosofer, fremmer Chalmers derfor et dualistisk syn på hjerne og bevissthet, naturalistic dualism, som imidlertid kan sies å ha fellestrekk med blant annet Bertrand Russells nøytrale monisme. Chalmers har også gitt viktige bidrag bl.a. til språkfilosofi og tolkning kvantemekanikkens paradokser. Chalmers besøker Oslo etter invitasjon av Centre for the Study of Mind in Nature, UiO (CSMN), og er invitert til vårt forum av professor Dagfinn Føllesdal. Møtet var lagt opp som en samtale med Chalmers om hjerne og bevissthet.

• Storm, Johan Frederik & Dehaene, Stanislas (2013). Signatures of conscious processing in the human brain. Show summary

  Sammen med Det Norske Videnskaps-Akademi, arrangerte forum for bevissthetsforskning et åpent møte med professor i kognitiv psykologi Stanislas Dehaene den 6. november. Mer en 150 deltakere møtte opp for å høre ham snakke om sin forskning på bevissthet. Dehaene holdt et foredrag om en serie eksperimenter han har gjort med sine samarbeidspartnere som forsøker å beskrive de endringene som skjer i hjernen når forsøkspersonene blir oppmerksom på ny informasjon. Forsøkene benytter små endringer i de eksperimentelle betingelsene som kan avgjøre om de samme stimuli blir registrert eller ikke. Det er, for eksempel, små endringer i hvor lenge et stimulus blir presentert for forsøkspersonene. Forskningen benytter EEG, fMRI og MEG for å studere endringer i hjernes aktivitet under disse eksperimentene. Resultatene fra Dehaenes forskning indikerer at bevissthet er forbundet med global økning i sen synkronisert aktivitet (en cortical «antenning») som er spredt over mange corticale områder. Sammen med sine medarbeidere har han utviklet en teori om et globalt nevronalt arbeidsminne eller -område i hjernen. I denne teorien er opplevelsen av bevissthet knyttet til tilgjengeligheten av informasjon i store nettverk i hjernen av pyramide-nevroner med langedistanse aksoner. Foredraget ble etterfulgt av en debatt ledet av Visepreses Nils Chr. Stenseth, og i panelet satt professor i nevrofysiologi Johan F. Storm, førsteamanuensis i psykologi Thomas Espeseth, post. doc. i filosofi Sebastian Watzl sammen med professor i kognitiv psykologi Stanislas Dehaene.

• Storm, Johan Frederik & Hu, Hua (2013). Robust propagation and initiation of dendritic action potentials in layer 2 stellate cells of the medial entorhinal cortex. Show summary

  Stellate cells (SCs) in layer 2 of the medial entorhinal cortex (mEC) display ‘grid’-like pattern of firing fields during spatial navigation, which is regarded as an essential neural mechanism for path integration. Computational models and experimental evidence have suggested that grid cell activity may depend on instrinsic biophysical processes within mEC stellate cells, including interference between dendritic and somatic subthreshold membrane potential oscillations. Therefore, examination of the biophysical properties of mEC stellate cell dendrites is fundamental for dissecting the mechanisms of grid formation. We performed simultaneous soma-dendritic or soma-axonal whole-cell recordings from rat mEC stellate cells (37 soma-dendritic and 13 soma-axonal recordings, respectively). We found that action potentials (APs) evoked by somatic depolarization were initiated in proximal axon (~ 25 µm from soma) and backpropagated into the dendrite (up to 151 µm) with little attenuation of their amplitude. In response to depolarizing input directly in the dendrite, APs could be initiated in both proximal (< 50 µm) and distal dendrites with high reliability. Tetrodotoxin (TTX) inhibited the initiation of dendritic APs, and strongly attenuated the amplitude of backpropagating APs. Spontaneous subthreshold membrane potential oscillations near theta frequency were measured in both the axon, dendrites and soma of mEC stellate cells. The membrane potential oscillations at these different subcellular compartments within the same stellate cell displayed identical oscillation frequency and were phase-locked to each other, with the proximal axon (~ 25 µm) displaying the strongest oscillation power. Thus, our results indicate that active dendritic properties support action potential backpropagation and initiation, and a putative axonal origin of subthreshold membrane potential oscillations in layer 2 mEC stellate cells.

• Tuvnes, Frode Alexander; Storm, Johan Frederik; Larsson, Pål Gunnar; Mateos-Aparicio, Pedro; Murphy, Ricardo; Oksvold, Cecilie Petterson; Höningsperger, Christoph & Fandango Kapperud, Åshild (2013). Hva skjer i hjernen din?. Show summary

  Hva skjer i hjernen din? Hva er hukommelse? Hva er bevissthet? Hva skjer i hjernen din når du føler noe? Hvordan kan elektriske impulser kode tanker? Hos oss kan du: - Se hjernebølger. - Se levende hjernevev og hjerneceller. - Se og høre hjernecellene sende signaler til hverandre. - Se matematiske modeller av hjernecellenes signaler. Akkurat nå, mens du leser denne teksten, farer milliarder av elektriske signaler gjennom cellene i hjernen din. Men hva er egentlig disse gåtefulle hjerneprosessene? Vår forskergruppe prøver å finne svarene. Kom og få et innbilkk i hva som foregår i hjernen din!

• Hönigsperger, Christoph; Marosi, Mate Gabor & Storm, Johan Frederik (2012). Characteristics of subthreshold membrane dynamics in dorsal and ventral CA1 pyramidal neurons. Show summary

  The hippocampus shows differences in neuronal connectivity and expression of molecular markers along the dorso-ventral axis. Behavioral and other studies indicate that the dorsal part of the hippocampus performs mainly cognitive functions, whereas the ventral corresponds to emotion and stress. The goal of our study is to determine whether there are differences in the intrinsic electrophysiological properties of dorsal and ventral CA1 pyramidal neurons. Using somatic whole-cell patch-clamp recordings from CA1 pyramidal neurons (n=78), we examined their ability to generate membrane potential oscillations (MPO) at subthreshold range and to respond selectively to oscillating current injections at different frequencies. We also compared repetitive firing evoked by depolarizing current steps. To study resonance at subthreshold potentials, we applied a frequency-modulated sinusoidal current whose frequency increased linearly in time. Our results showed that the majority of dorsal CA1 pyramidal neurons (n=22/30) have a prominent resonance peak (frequency: 2.5±0.3Hz) compared to the ventral side where only few cells (n=7/30) showed detectable resonance, and the resonance frequency was lower (0.8±0.2Hz). We also observed a statistically significant difference in frequency of MPOs at subthreshold potentials (dorsal: 3.4±0.3Hz; ventral: 2.3±0.2Hz). MPOs in CA1 pyramidal neurons are probably generated by interplay of a persistent Na+ current and slowly deactivating K+ current, and it has been shown that subthreshold theta resonance in these cells is generated by persistent Na+ current and Kv7/M-type K+ channels. The Kv7 channels also regulate excitability, spike afterpotentials, and spike frequency adaptation. We hypothesized that Kv7 channels may also contribute to the generation of spontaneous oscillations (MPO) and tested the effect of XE991 (selective Kv7 channel blocker). Application of XE991 lowered the threshold and eliminated MPOs. Our findings indicate that the biophysical properties of CA1 pyramidal cells differ along the dorso-ventral axis, and that MPOs are Kv7-dependent in this cell type.

• Larsson, Pål Gunnar; Stavrinou, ML; Kugiumtzis, Dimitris & Storm, Johan Frederik (2012). PERSISTENT CONNECTIVITY DURING AWAKE AND SLEEP OF BRAIN LOCATIONS GENERATING CONTINUOUS SPIKE AND WAVES DURING SLOW SLEEP (CSWS). Epilepsia.  ISSN 0013-9580.  53, s 237- 237
• Mateos-Aparicio, Pedro & Storm, Johan Frederik (2012). Dorsoventral differences in the slow after-hyperpolarization of dentate gyrus granule cells.
• Murphy, Ricardo; Alle, Henrik; Geiger, Jörg & Storm, Johan Frederik (2012). Estimation of persistent sodium and M current densities in poorly space-clamped dentate granule-cell mossy fibers.
• Stavrinou, Maria; Larsson, Pål Gunnar & Storm, Johan Frederik (2012). Increased temporo-parietal connectivity in children with ADHD and CSWS. Show summary

  Attention-Deficit hyperactivity disorder (ADHD) is one of the most common neuropsychiatric conditions in childhood. It is characterized by inappropriate expression of impulsivity, inattention and hyperactivity. A per- centage of children with ADHD appear to have continuous spikes and waves during their sleep a condition most often called Continuous spike and waves during slow sleep (CSWS). One of the hypotheses used to explain the affected cognitive functioning of those children concerns changes in resting-state connectivity. In this framework, we studied the functional and effective brain connectivity in children with ADHD and CSWS, focusing on the resting state network with Electroencephalographic recordings. Twenty four-hour recordings including wakefulness and sleep, of children admitted to the National Centre for Epilepsy at Oslo University Hospital were analyzed and compared with controls of the same age group without ADHD. Di- rected transfer function (DTF) was used to measure the effective connectivity between brain areas, in the theta and gamma frequency bands. The analysis have shown an increased temporo-parietal connectivity of the ADHD children, when compared to the control group (p<0.035), most prominently in the left hemi- sphere. Parietal to frontal connections were also significantly different between patients and controls for both frequency bands. The time dynamics of these most active connections have shown increased values of connectivity during the day compared to sleep. This may be related to arousal impairment in children with ADHD.

• Murphy, Ricardo & Storm, Johan Frederik (2011). Correction of space-clamp errors in voltage-clamp experiments on neurons: Extension of Cox’s method.
• Murphy, Ricardo; Ostroumov, Konstantin & Storm, Johan Frederik (2010). Modeling predicts subthreshold resonance filtering of information transfer along axons.
• Giglio, Anna Maria & Storm, Johan Frederik (2010). Postnatal development of alpha-DTX sensitive D-current in rat CA1 hippocampal pyramidal cells.
• Moreno, Pedro Mateos Aparicio; Tuvnes, Frode Alexander & Storm, Johan Frederik (2010). SK channels underlying medium afterhyperpolarizations and excitability control in dentate gyrus granule cells.
• Moreno, Pedro Mateos Aparicio; Tuvnes, Frode Alexander & Storm, Johan Frederik (2010). SK channels underlying medium afterhyperpolarizations and excitability control in dentate gyrus granule cells.
• Storm, Johan Frederik; Alle, Henrik & Geiger, Jörg RP (2010). Subthreshold resonance caused by M-current and persistent sodium current recorded in mossy fiber boutons (MFBs) in rat hippocampus.
• Liao, Yiliu; Kristiansen, Åse-Marit; Oksvold, Cecilie Petterson; Tuvnes, Frode Alexander; Gu, Ning; Rundén-Pran, E.; Ruth, Peter; Sausbier, M & Storm, Johan Frederik (2009). Neuronal Ca2+-activated K+ channels limit brain infarction and promote survival.
• Alle, Henrik; Ostroumov, Konstantin; Geiger, Jörg & Storm, Johan Frederik (2009). M-current, persistent Na+ current, and subthreshold resonance recorded in mossy fiber boutons (MFBs) in rat hippocampus.
• Giglio, Anna Maria & Storm, Johan Frederik (2009). Postnatal development of D-current-dependent delayed excitation and temporal integration in rat CA1 hippocampal pyramidal cells.
• Hu, Hua; Vervaeke, Koen Gerard Alois; Graham, L & Storm, Johan Frederik (2009). Dual, complementary theta resonance filtering in hippocampal pyramidal neurons.
• Storm, Johan Frederik & Gundersen, S. (2009). Hvordan kan fysiske hjerneprosesser gi opphav til bevissthet?. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  (9) . doi: 10.4045/tidsskr.09.0070 Show summary

  Vår bevissthet skyldes hjerneprosesser og omfatter hele vår subjektive verden: Alt vi sanser, føler, tenker og husker. Men hvordan kan fysiske prosesser i hjernen gi opphav til vår bevissthet – et fenomen som ikke synes å passe inn i vårt naturvitenskapelige verdensbilde? De siste årene har brakt en ny bølge av interesse for dette dype mysteriet. Nye metoder for kartlegging av hjerneaktivitet hos våkne mennesker har tent håp om fremgang. (Og endelig har vi funnet plass til dette temaet også i medisinstudiet, i Oslo.) Men kan mysteriet løses med naturvitenskapelige metoder? Ståle Gundersen, som er førsteamanuensis i filosofi ved Universitetet i Stavanger, tar for seg disse store spørsmålene. Han gir en god oversikt over sentrale filosofiske teorier, og presenterer så sitt eget syn. Forfatteren henvender seg til et bredt publikum, inkludert studenter og forskere innen filosofi, psykologi, naturvitenskap og samfunnsfag, og er både konsis og dyptpløyende. Spesielt interessant er det at Gundersen gjør seg til talsmann for et relativt radikalt filosofisk standpunkt som man sjelden ser hevdet (men som jeg lenge har hatt interesse for): nøytral monisme. Ifølge monismen er bevissthet identisk med visse hjerneprosesser. Den forkaster altså forstillingen om at psyke og soma er radikalt forskjellige. Et slikt monistisk standpunkt er i seg selv ikke uvanlig; tvert imot, det dominerer dagens filosofiske debatt. Men de aller fleste monister hevder at bevisstheten «egentlig bare» er noe fysisk; de er fysikalister. Nøytrale monister derimot, argumenterer for at virkeligheten i seg selv neppe er verken rent fysisk eller rent mental; den er trolig «nøytral», men gir opphav til forestillingene om både det mentale og det fysiske: To tilsynelatende uforenlige måter å beskrive den samme nøytrale virkeligheten på. Dermed ses bevissthetsproblemet i lys av et generelt erkjennelsesproblem som allerede Kant («Ding an sich/Ding für mich»), Bertrand Russell og andre har påpekt: At vi aldri kan få direkte kjennskap til noe i den ytre, materielle verden. Våre opplevelser bygger jo på indirekte informasjon gjennom sanse- og hjerneprosesser, kodet i signaler som er vesensforskjellige fra det de representerer. Din oppfatning av verden, inkludert din egen kropp, er derfor konstruert av din hjerne, som en «modell» eller et «kart» over det som finnes der ute. Det eneste vi kan forvente er strukturlikhet mellom den ytre verden og vår bevisste opplevelse av den. Det er prisverdig at Gundersen så sterkt vektlegger dette perspektivet, som jeg har savnet i andre nyere bøker om bevissthet. Likevel synes det tvilsomt om det er meningsfullt å hevde at de minste fysiske bestanddeler må ha iboende egenskaper som kan gi opphav til bevissthet når de kombineres. Det virker også for meg noe for upresist og pessimistisk å si at «hjerne-bevissthets-problemet vil forbli uløselig» ettersom vi ikke kan oppnå kunnskap om disse tilgrunnliggende egenskapene. Her er det vel (som så ofte ellers) rom for ulike grader av forståelse, og tross alt håp om at vi i betydelig grad kan øke vår forståelse og kunnskap, spesielt om hvilke typer hjerneprosesser som gir opphav til bevissthet, til forskjell fra de mange som er ubevisste. Jeg savner en grundigere diskusjon av slike nevrale korrelater til bevissthet. Og ikke minst: Jeg savner en drøfting av begrensningene i vår menneskelige intuisjon og dermed den fundamentale usikkerheten i alle våre filosofiske spekulasjoner. Men alt i alt er dette en bok som jeg varmt vil anbefale alle som er fascinert av det som er blitt kalt «den største intellektuelle utfordring i det nye årtusen» (1). Litteratur 1. Dehaene S, Changeux JP. Neural mechanisms for access to consciousness. I: Gazzaniga M, red. The cognitive neurosciences. 3. utg. New York: Norton, 2004:1145-57

• Lindén, Henrik & Storm, Johan Fredrik (2008, 28. september). Ry i Radio Nova: Portrett av Johan Storm. Show summary

  Detta program av Ry handlar om hjärnforskning. Vad betyder det för vår bild av oss själva att vi förstår mer om hjärnan? Vilka etiska konsekvenser kan det få? Och har vi verkligen en fri vilja om det som händer i hjärnan styrs av fysiska lagar? Ry har intervjuat Prof. Johan Storm vid Senter for molekylærbiologi och nevrovitenskap vid Universitet i Oslo. Programmet sändes söndag 28. sept kl. 14.30 med repris fredag 3. okt kl. 11.00. Programansvarig är Henrik Lindén.

• Elster, Jakob; Roll-Hansen, Nils & Storm, Johan Frederik (2008). Upop-aften: Nevroetikk.
• Ning, Gu & Storm, Johan Frederik (2008). Roles of potassium channels in excitability control and spike adaptation in hippocampal pyramidal cells.
• Cheron, G; Servais, L; Cebolla, A.; Dufiei, M; Dan, B; Sausbier, M; Storm, Johan Frederik & Ruth, P (2007). Altered Purkinje cell firing phase-locked to beta oscillation in the cerebellar cortex of mice lacking BK channels. Show summary

  Since Purkinje cells constitute the sole output of the cerebellar cortex, the regulation of their firing through synaptic inputs and intrinsic excitability is central for motor coordination. This intrinsic excitability is mainly driven by resurgent Na+ channels, but also by voltage-gated calcium channels and calcium-activated potassium channels. Calcium-activated potassium channels expressed by Purkinje cells are divided in small (SK) and large (BK) conductance channels. The specificity of BK channels is that they require both depolarization and increased intracellular Ca++ for maximal activation. BK channel blockade in vitro leads to slight simple spike firing rate increase if applied during tonic firing and to complex modification of burst pattern if applied during bursting period. To further understand how BK channels intervene in the Purkinje cell firing properties, and thus in the cerebellar function, mice deficient for the BK channels (BK-/-) have been generated. In slice preparation, the Purkinje cells of BK-/- mice demonstrate a dramatic decrease in spontaneous firing. This decrease is partially explained by the increased proportion of the time spent by these cells in the silent mode when compared with the Purkinje cells of the controls that normally express BK channels. In addition, the paired-pulse depression at the Purkinje cell-deep cerebellar neurons is largely increased. These two observations have led to the hypothesis that the major motor coordination impairment observed in BK-/- mice could result from a decreased net inhibition of deep cerebellar nuclei by the Purkinje cells. To test this hypothesis, we recorded the spontaneous and stimulus-evoked activity of Purkinje cells in alert BK-/- mice and in wild-type controls. We found that Purkinje cell activity is only mildly decreased in BK-/- mice, but that their cerebellum presents a beta rhythm local field potential oscillation phase-locked with ultra-rhythmic Purkinje. We demonstrated the existence of BK channels in Golgi cells, which could partly explain the phase-locking of these cells to the abnormal beta rhythm in BK-/-mice. We also demonstrated that this Purkinje cell firing pattern and the ataxic behavior of BK-/- mice were reproduced in vivo by microinjection of BK channels blocker in WT mice cerebellum.

• Gu, Ning; Ostroumov, Konstantin; Sharifullina, Elina & Storm, Johan Frederik (2007). Subthreshold theta oscillations in hippocampal CA1 pyramidal cells mediated by Kv7/KCNQ/M potassium current and persistent sodium (NaP) currents. Show summary

  Hippocampal theta oscillations (5-10 Hz) occur during exploration, learning behavior and REM sleep, and are hypothesized to play important roles in neuronal coding, learning and memory. We previously showed that CA1 pyramidal cells are equipped with two mechanisms for intrinsic subthreshold electrical resonance (J. Physiol. 545:783-805, 2002): (1) M-resonance mediated by Kv7/KCNQ/M-type K+ current and persistent Na+ (NaP) current, and (2) H-resonance mediated by HCN/h current. Using sharp electrode intracellular and whole cell patch recordings from CA1 pyramidal cells in rat hippocampal slices, we have now studied the mechanisms of spontaneous subthreshold theta oscillations evoked by steady depolarization and slow depolarizing ramps. When the CA1 cells were depolarized beyond - 60 mV, in the presence of blockers of fast synaptic transmission (DNQX, APV and gabazine) they showed spontaneous subthreshold membrane potential oscillations (MPO) in the theta frequency range, and typical M-resonance. Thus, injection of an oscillating current with increasing frequency (ZAP) evoked MPOs with a resonance peak in the theta frequency range. The spontaneous MPOs and resonance were suppressed by 1 uM TTX, which blocks INaP (n=8). They were also fully suppressed by the M-channel blocker XE991 (10 uM) (n=5), wheras the M-channel opener retigabine (10 uM) enhanced the spontaneous subthreshold theta oscillations and M-resonance (n=7) as expected for M-current dependent processes. In contrast, when the cell was hyperpolarized (-70 to -80 mV) there were no spontaneous theta oscillations and the theta resonance at those potentials was not blocked by XE991 or TTX, but was suppressed by the h-channel blocker ZD7288, which also blocked the sag in response to hyperpolarizing pulses (n=6). The muscarinic agonist carbachol (30 uM) blocked the MPO, the M-resonance (n=20) and the medium AHP (mAHP) following a spike burst (n=12). In contrast, carbachol did not block the H-resonance observed when the cell was hyperpolarized (-70 to -80 mV). These results indicate that CA1 hippocampal pyramidal cells, when depolarized to potentials just subthreshold for spike generation, generate spontaneous theta oscillations caused by M- and NaP-currents, but not HCN/h currents. These mechanisms are likely to contribute to hippocampal theta oscillations, and hippocampus-dependent learning and memory.

• Gu, Ning & Storm, Johan Frederik (2007). FEED-BACK REGULATION OF GLUTAMATE RELEASE BY PRESYNAPTIC BK POTASSIUM CHANNELS IS ENHANCED UNDER LOW OXYGENATION CONDITIONS IN RAT HIPPOCAMPUS (CA1).

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