Koen Gerard Alois Vervaeke

• Bojarskaite, Laura; Bjørnstad, Daniel Marelius; Pettersen, Klas Henning; Cunen, Celine; Hermansen, Gudmund Horn; Åbjørsbråten, Knut Sindre; Chambers, Anna; Sprengel, Rolf; Vervaeke, Koen Gerard Alois; Tang, Wannan; Enger, Rune & Nagelhus, Erlend Arnulf (2020). Astrocytic Ca2+ signaling is reduced during sleep and is involved in the regulation of slow wave sleep. Nature Communications.  ISSN 2041-1723.  11 . doi: 10.1038/s41467-020-17062-2 Full text in Research Archive.
• Hu, Hua & Vervaeke, Koen Gerard Alois (2017). Synaptic integration in cortical inhibitory neuron dendrites. Neuroscience.  ISSN 0306-4522.  368, s 115- 131 . doi: 10.1016/j.neuroscience.2017.06.065
• Morland, Cecilie; Andersson, Krister; Haugen, Øyvind Pernell; Hadzic, Alena; Kleppa, Liv; Gille, Andreas; Rinholm, Johanne Egge; Palibrk, Vuk; Diget, Elisabeth Holm; Kennedy, Lauritz Hagen; Stølen, Tomas; Hennestad, Eivind; Moldestad, Olve; Cai, Yiqing; Puchades, Maja Amedjkouh; Offermanns, Stefan; Vervaeke, Koen Gerard Alois; Bjørås, Magnar; Wisløff, Ulrik; Storm-Mathisen, Jon & Bergersen, Linda Hildegard (2017). Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1. Nature Communications.  ISSN 2041-1723.  8 . doi: 10.1038/ncomms15557 Full text in Research Archive. Show summary

  Physical exercise can improve brain function and delay neurodegeneration; however, the initial signal from muscle to brain is unknown. Here we show that the lactate receptor (HCAR1) is highly enriched in pial fibroblast-like cells that line the vessels supplying blood to the brain, and in pericyte-like cells along intracerebral microvessels. Activation of HCAR1 enhances cerebral vascular endothelial growth factor A (VEGFA) and cerebral angiogenesis. High-intensity interval exercise (5 days weekly for 7 weeks), as well as L-lactate subcutaneous injection that leads to an increase in blood lactate levels similar to exercise, increases brain VEGFA protein and capillary density in wild-type mice, but not in knockout mice lacking HCAR1. In contrast, skeletal muscle shows no vascular HCAR1 expression and no HCAR1-dependent change in vascularization induced by exercise or lactate. Thus, we demonstrate that a substance released by exercising skeletal muscle induces supportive effects in brain through an identified receptor. Editorial summary: Physical exercise promotes brain angiogenesis through an unknown signalling cascade. Morland et al. identify the elusive muscle-brain communication and show that lactate produced by muscle activity binds to its receptor HCAR1 in brain vessel-surrounding cells, stimulating VEGF production and brain angiogenesis.

• Enger, Rune; Dukefoss, Didrik Bakke; Tang, Wannan; Pettersen, Klas; Bjørnstad, Daniel Marelius; Helm, Paul Johannes; Jensen, Vidar; Sprengel, Rolf; Vervaeke, Koen Gerard Alois; Ottersen, Ole Petter & Nagelhus, Erlend Arnulf (2016). Deletion of aquaporin-4 curtails extracellular glutamate elevation in cortical spreading depression in awake mice. Cerebral Cortex.  ISSN 1047-3211. . doi: 10.1093/cercor/bhw359
• Rinholm, Johanne Egge; Vervaeke, Koen Gerard Alois; Tadross, Michael; Tkachuk, Ariana; Kopek, Benjamin; Brown, Timothy A; Bergersen, Linda Hildegard & Clayton, David A (2016). Movement and structure of mitochondria in oligodendrocytes and their myelin sheaths. Glia.  ISSN 0894-1491.  64(5), s 810- 825 . doi: 10.1002/glia.22965 Show summary

  Mitochondria play several crucial roles in the life of oligodendrocytes. During development of the myelin sheath they are essential providers of carbon skeletons and energy for lipid synthesis. During normal brain function their consumption of pyruvate will be a key determinant of how much lactate is available for oligodendrocytes to export to power axonal function. Finally, during calcium-overload induced pathology, as occurs in ischemia, mitochondria may buffer calcium or induce apoptosis. Despite their important functions, very little is known of the properties of oligodendrocyte mitochondria, and mitochondria have never been observed in the myelin sheaths. We have now used targeted expression of fluorescent mitochondrial markers to characterize the location and movement of mitochondria within oligodendrocytes. We show for the first time that mitochondria are able to enter and move within the myelin sheath. Within the myelin sheath the highest number of mitochondria was in the cytoplasmic ridges along the sheath. Mitochondria moved more slowly than in neurons and, in contrast to their behavior in neurons and astrocytes, their movement was increased rather than inhibited by glutamate activating NMDA receptors. By electron microscopy we show that myelin sheath mitochondria have a low surface area of cristae, which suggests a low ATP production. These data specify fundamental properties of the oxidative phosphorylation system in oligodendrocytes, the glial cells that enhance cognition by speeding action potential propagation and provide metabolic support to axons.

• Szoboszlay, Miklos; Lőrincz, Andrea; Lanore, Fredereic; Vervaeke, Koen Gerard Alois; Silver, R Angus & Nusser, Zoltan (2016). Functional properties of dendritic gap junctions in cerebellar golgi cells. Neuron.  ISSN 0896-6273.  90(5), s 1043- 1056 . doi: 10.1016/j.neuron.2016.03.029
• Vervaeke, Koen Gerard Alois; lörincz, Andrea; Nusser, Zoltan & Silver, R (2012). Gap Junctions Compensate for Sublinear Dendritic Integration in an Inhibitory Network.. Science.  ISSN 0036-8075.  335(6076), s 1624- 1628 . doi: 10.1126/science.1215101
• Vervaeke, Koen Gerard Alois; lörincz, Andrea; Gleeson, Padraig; Farinella, Matteo; Nusser, Zoltan & Silver, R (2010). Rapid Desynchronization of an Electrically Coupled Interneuron Network with Sparse Excitatory Synaptic Input.. Neuron.  ISSN 0896-6273.  67(3), s 349- 522 . doi: 10.1016/j.neuron.2010.06.028
• 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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• Kriener, Birgit; Hu, Hua & Vervaeke, Koen Gerard Alois (2018). Dendritic properties of parvalbumin interneurons enhance robustness of gamma oscillations.
• Kriener, Birgit; Hu, Hua & Vervaeke, Koen Gerard Alois (2018). Stabilization of gamma oscillations in basket cell networks: the role of dendritic attenuation.
• Morland, Cecilie; Andersson, Krister; Haugen, Øyvind Pernell; Hadzic, Alena; Kleppa, Liv; Gille, Andreas; Rinholm, Johanne Egge; Diget, Elisabeth Holm; Kennedy, Lauritz Hagen; Stølen, Tomas; Hennestad, Eivind; Cai, Yiqing; Puchades, Maja Amedjkouh; Offermanns, Stefan; Vervaeke, Koen Gerard Alois; Wisløff, Ulrik; Storm-Mathisen, Jon & Bergersen, Linda Hildegard (2016). A novel mechanism for cerebral angiogenesis via lactate receptor HCAR1 at pial vessels.
• Morland, Cecilie; Andersson, Krister; Haugen, Øyvind Pernell; Hadzic, Alena; Kleppa, Liv; Gille, Andreas; Rinholm, Johanne Egge; Elisabeth, Holm Diget; Kennedy, Lauritz Hagen; Stølen, Tomas; Hennestad, Eivind; Cai, Yiqing; Puchades, Maja Amedjkouh; Offermanns, Stefan; Vervaeke, Koen Gerard Alois; Wisløff, Ulrik; Storm-Mathisen, Jon & Bergersen, Linda Hildegard (2016). Exercise induces cerebral angiogenesis via lactate receptor HCAR1 at pial vessels.
• Dragly, Svenn-Arne; Ness, Torbjørn Vefferstad; Vervaeke, Koen Gerard Alois & Einevoll, Gaute (2015). Discovering extracellular signatures by modeling of local field potentials.
• Hobbi Mobarhan, Milad; Einevoll, Gaute; Geir, Halnes; Vervaeke, Koen Gerard Alois & Fyhn, Marianne (2015). Roles of cortical feedback in lateral geniculate nucleus.
• Hu, Hua; Vervaeke, Koen Gerard Alois; Graham, L & Storm, Johan Frederik (2009). Dual, complementary theta resonance filtering in hippocampal pyramidal neurons.
• Hu, Hua; Vervaeke, Koen Gerard Alois & Storm, Johan Frederik (2007). Theta resonance regulates frequency-dependence of postsynaptic responses and signal transfer along the apical dendrites of hippocampal pyramidal cells.
• Storm, Johan Frederik & Vervaeke, Koen Gerard Alois (2007). Effects of sub-threshold activated ion channels on signal integration in hippocampal pyramidal neurons. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  (15)
• Vervaeke, Koen Gerard Alois; Peters, C; Isbrandt, Dirk & Storm, Johan Frederik (2007). Evidence that KCNQ2-containing M-channels underlie a major component of the presynaptic M-current in hippocampal glutamatergic axons.
• Vervaeke, Koen Gerard Alois; Sharifullina, Elina & Storm, Johan Frederik (2007). Mechanisms and cholinergic modulation of subthreshold theta resonance, after-hyperpolarizations (mAHP), and bursting in hippocampal CA3 pyramidal cells. Show summary

  CA3 hippocampal pyramidal cells are hypothesized to play important roles in theta oscillations (5-10 Hz), learning and memory, but relatively little is known about subthreshold theta resonance and after-hyperpolarization (AHP) mechanisms in these cells, although these processes may be important for theta oscillatons and plasticity. Using whole cell patch clamp and sharp electrode intracellular recordings in rat hippocampal slices, we have now found that CA3 pyramidal cells are equipped with two mechanisms for intrinsic subthreshold electrical resonance, similar to those found in CA1 pyramidal cells (Hu et al., J. Physiol. 545:783-805, 2002): (1) M-resonance mediated by Kv7/KCNQ/M-type K+ current and persistent Na+ current (INaP), and (2) H-resonance mediated by HCN/h current. Thus, when cells were depolarized beyond -60 mV, after blocking fast synaptic transmission, 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. They were also fully suppressed by 30 uM carbachol (n=7), and recovered after addition of 1 uM atropine, as expected for muscarinic suppression of M-current dependent processes. In contrast, H-resonance, observed when the cell was hyperpolarized (-70 to -80 mV) was not blocked by carbachol or TTX, but was fully suppressed by the h-channel blocker ZD7288, which also blocked the sag in response to hyperpolarizing pulses (n=5). Carbachol or the M-channel blocker XE991 (10 uM) also increased the number and frequency of spikes evoked by depolarizing current pulses, blocked the medium AHP (mAHP) following a spike burst, enhanced the afterdepolarization (ADP) and enhanced bursting, but did not block the slow AHP. Following spike bursts evoked in XE991, a biphasic AHP appeared, the early phase of which was suppressed by apamin (10 uM), suggesting SK channel activation. These results indicate that CA3 hippocampal pyramidal cells are equipped with voltage-dependent dual mechanisms of theta resonance: M- and H-resonance, caused by M-, NaP- and h-currents (Hu et al., 2002), and in addition M-current-dependent mAHP and spike frequency adaptation mechanisms, similar to those found in CA1 cells (Gu et al., J. Physiol. 566: 689-715, 2005). In addition, the CA3 pyramidal cells show an early SK channel-dependent AHP following M-channel suppression. These mechanisms are likely to contribute to hippocampal theta oscillations, learning and memory.

• Vervaeke, Koen Gerard Alois & Storm, Johan Frederik (2007). Effects of sub-threshold activated ion channels on signal integration in hippocampal pyramidal neurons.
• Vervaeke, Koen Gerard Alois; Gu, Ning & Storm, Johan Frederik (2006). Large conductance calcium activated K+ (BK) channels promote high-frequency firing in rat CA1 hippocampal pyramidal neurons. Show summary

  Potassium (K+) channels normally reduce neuronal excitability. However, during previous experiments, blockade of the BK-type calcium-activated K+ channels in rat CA1 pyramidal cells reduced the initial discharge frequency in response to current injection (Storm, unpublished) - an effect attributed to increased Na+ channel inactivation and K+ channel activation following suppression of BK-dependent spike repolarization and fast afterhyperpolarization (fAHP; Storm, J.Physiol. 1987). However, other reports have suggested that BK channel blockade increases the initial spike frequency and reduces the post-burst medium afterhyperpolarization (mAHP). We have re-examined the functions of BK channels during high-frequency repetitive firing in rat CA1 pyramidal cells in slices. Blockade of BK channels by IbTX (100 nM) reduced the frequency of the initial discharge in response to strong depolarizing current pulse injections. E.g., in response to 0.8-1.0 nA current pulses, IbTX reduced the frequency of the first inter-spike interval (ISI-1) from 169±5 to 146±6 Hz (n=6, p=0.02), and the average frequency of ISIs 1-3 from 122±4 Hz to 103±3 Hz (n=6, p=0.001). In contrast, IbTX had little or no effect on lower-frequency repetitive firing (~ 40-70 Hz) in response to weaker depolarizing current. IbTX also failed to significantly change the amplitude of the mAHP following a train of 5 spikes (n=5, p>0.05), However, IbTX application significantly reduced the decay slope of both the first and second action potentials (APs) in each train (both: p0.05), the rising slope of the 2nd AP was significantly reduced by BK channel blockade (n=5, P<0.05). Simulations with a computational model of a CA1 pyramidal cell confirmed that the BK channel-mediated rapid spike repolarization and fAHP limits both activation of other K+ channels and Na+ channel inactivation and promotes recovery from Na+ inactivation through hyperpolarization, thus reducing post-spike refractoriness and promoting high-frequency firing. The simulations predicted that this occurs without noticeably affecting post-burst mAHPs. We conclude that BK channels can have an “excitatory” effect by counteracting Na+ channel inactivation and activation of other K+ channels, thus facilitating high frequency discharge.

• Vervaeke, Koen Gerard Alois; Hu, Hua; Graham, LJ & Storm, Johan Frederik (2005). Persistent sodium current modulates temporal precision of action potential discharge in CA1 pyramidal cells. Show summary

  The temporal precision with which synaptic input initiates action potentials is likely to be important for neuronal information coding. By combining whole cell recording/dynamic clamp experiments and computer modeling, we studied the contribution of the persistent Na+ current (INaP) to the temporal precision of excitatory postsynaptic potential (EPSP)-triggered action potentials in CA1 pyramidal neurons. Stimulation with an electrode placed in str. radiatum evoked EPSPs in CA1 pyramidal neurons. The stimulus strength was carefully adjusted, so that only ~ 45% of the EPSPs triggered an action potential, under each experimental condition. In the control condition, CA1 pyramidal neurons showed high variability in their EPSP-triggered spike timing (Var = 111.2+/-40.1 ms, n=8). When we cancelled the cell's intrinsic INaP with dynamic clamp, the temporal precision of discharge significantly increased (Var = 2.6+/-0.4 ms, n=8, p=0.03). Also, the rise and decay of subthreshold EPSPs were significantly accelerated when INaP was cancelled (n=8, p<0.05). Similar results were obtained with a computational model of a CA1 pyramidal cell. In conclusion, our results indicate that INaP strongly modulates subthreshold EPSP time course and temporal precision of spike discharge in CA1 pyramidal neurons.

• Vervaeke, Koen Gerard Alois & Storm, Johan Frederik (2003). Modulation of theta - resonance in hippocampal CA1 pyramidal cells by neurotransmitters acting via H - , leak and GIRK channels. Show summary

  Theta oscillations are suggested to be important for hippocampus-dependent spatial navigation, learning and memory (Buzsaki, Neuron, 33:325-40, 2002), and may result from an interplay between synaptic input and intrinsic resonance properties of hippocampal neurons. We recently showed by experiments and computational modelling that there are two forms of theta resonance of CA1 pyramidal cells: M-resonance generated (at depolarized potentials) primarily by the M current and H-resonance generated (at more negative potentials) by the H current (Hu et al., J.Physiol. 545:783-805, 2002). These resonance properties are likely to be subject to state-dependent modulation, in particular by ascending neurotransmitter systems from the brainstem and basal forebrain, e.g. during arousal, sleep or fatigue. Here, we explore the effects of neuromodulation on theta resonance in the CA1 pyramidal cell model. Introducing the muscarinic suppression of a leak conductance, as would occur during cholinergic input (Nicoll, Science 241:545, 1988), caused a marked enhancement of the M-resonance at -60 mV, and a more modest increase in H resonance at -80 mV. Likewise, cyclic-AMP-dependent depolarizing shift in H-channel activation, as would occur through infuence from ascending monoaminergic fibres (Pedarzani & Storm, PNAS 92:11716,1995), caused an increase in the strength and frequency of the H-type theta resonance, but with no change in M-resonance. In contrast, introducing a G-protein-activated inward rectifier K+ (GIRK) conductance, as would occur through influence from inhibitory GABAergic (GABAb-Rs), serotonergic (5-HT-1A-Rs) or purinergic (adenosine), caused a marked reduction in the strength of both M-type and H-type theta resonance, combined with a slight increase in the resonance frequency. We conclude that different forms of neuromodulation can alter theta resonance in hippocampal pyramidal cells in diverse ways.

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