Differential chloride homeostasis in the spinal dorsal horn locally shapes synaptic metaplasticity and modality-specific sensitization.
Animals
Cells, Cultured
Central Nervous System Sensitization
/ physiology
Chlorides
/ metabolism
Male
Membrane Glycoproteins
/ antagonists & inhibitors
Mice
Models, Neurological
Neuronal Plasticity
/ physiology
Nociception
/ physiology
Optogenetics
Posterior Horn Cells
/ physiology
Primary Cell Culture
Protein-Tyrosine Kinases
/ antagonists & inhibitors
Rats
Receptor, trkB
/ antagonists & inhibitors
Symporters
/ metabolism
K Cl- Cotransporters
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 08 2020
07 08 2020
Historique:
received:
05
12
2018
accepted:
22
07
2020
entrez:
10
8
2020
pubmed:
10
8
2020
medline:
22
9
2020
Statut:
epublish
Résumé
GABA
Identifiants
pubmed: 32769979
doi: 10.1038/s41467-020-17824-y
pii: 10.1038/s41467-020-17824-y
pmc: PMC7414850
doi:
Substances chimiques
Chlorides
0
Membrane Glycoproteins
0
Symporters
0
Ntrk2 protein, mouse
EC 2.7.10.1
Ntrk2 protein, rat
EC 2.7.10.1
Protein-Tyrosine Kinases
EC 2.7.10.1
Receptor, trkB
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3935Subventions
Organisme : CIHR
ID : MOP 12942
Pays : Canada
Organisme : CIHR
ID : FDN 159906
Pays : Canada
Références
Fritschy, J. M. & Panzanelli, P. GABAA receptors and plasticity of inhibitory neurotransmission in the central nervous system. Eur. J. Neurosci.39, 1845–1865 (2014).
pubmed: 24628861
Zeilhofer, H. U., Benke, D. & Yevenes, G. E. Chronic pain states: pharmacological strategies to restore diminished inhibitory spinal pain control. Annu. Rev. Pharmacol. Toxicol.52, 111–133 (2012).
pubmed: 21854227
Kaila, K., Voipio, J., Paalasmaa, P., Pasternack, M. & Deisz, R. A. The role of bicarbonate in Gaba-A receptor-mediated Ipsps of rat neocortical neurons. J. Physiol.464, 273–289 (1993).
pubmed: 8229801
pmcid: 1175385
Blaesse, P., Airaksinen, M. S. & Rivera, C., . & Kaila, K. Cation-chloride cotransporters and neuronal function. Neuron61, 820–838 (2009).
pubmed: 19323993
Doyon, N., Vinay, L., Prescott, S. A. & De Koninck, Y. Chloride regulation: a dynamic equilibrium crucial for synaptic inhibition. Neuron89, 1157–1172 (2016).
pubmed: 26985723
Huberfeld, G. et al. Perturbed chloride homeostasis and GABAergic signaling in human temporal lobe epilepsy. J. Neurosci.27, 9866–9873 (2007).
pubmed: 17855601
pmcid: 6672644
Boulenguez, P. et al. Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury. Nat. Med.16, 302–U397 (2010).
pubmed: 20190766
Hyde, T. M. et al. Expression of GABA signaling molecules KCC2, NKCC1, and GAD1 in cortical development and Schizophrenia. J. Neurosci.31, 11088–11095 (2011).
pubmed: 21795557
pmcid: 3758549
Hewitt, S. A., Wamsteeker, J. I., Kurz, E. U. & Bains, J. S. Altered chloride homeostasis removes synaptic inhibitory constraint of the stress axis. Nat. Neurosci.12, 438–443 (2009).
pubmed: 19252497
Ostroumov, A. et al. Stress increases ethanol self-administration via a shift toward excitatory GABA signaling in the ventral tegmental area. Neuron92, 493–504 (2016).
pubmed: 27720487
pmcid: 5091663
Taylor, A. M. et al. Neuroimmune regulation of GABAergic neurons within the ventral tegmental area during withdrawal from chronic morphine. Neuropsychopharmacology41, 949–959 (2016).
pubmed: 26202104
Coull, J. A. M. et al. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature438, 1017–1021 (2005).
pubmed: 16355225
Coull, J. A. M. et al. Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature424, 938–942 (2003).
pubmed: 12931188
De Koninck, Y. Altered chloride homeostasis in neurological disorders: a new target. Curr. Opin. Pharmacol.7, 93–99 (2007).
pubmed: 17182282
Gagnon, M. et al. Chloride extrusion enhancers as novel therapeutics for neurological diseases. Nat. Med.19, 1524–1528 (2013).
pubmed: 24097188
pmcid: 4005788
Keller, A. F., Beggs, S., Salter, M. W. & De Koninck, Y. Transformation of the output of spinal lamina I neurons after nerve injury and microglia stimulation underlying neuropathic pain. Mol. Pain3, 27 (2007).
Lavertu, G., Cote, S. L. & De Koninck, Y. Enhancing K-Cl co-transport restores normal spinothalamic sensory coding in a neuropathic pain model. Brain137, 724–738 (2014).
pubmed: 24369380
Lalisse, S. et al. Sensory neuronal P2RX4 receptors controls BDNF signaling in inflammatory pain. Sci. Rep.8, 964 (2018).
pubmed: 29343707
pmcid: 5772667
Ferrini, F. et al. Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl(-) homeostasis. Nat. Neurosci.16, 183–192 (2013).
pubmed: 23292683
pmcid: 4974077
Ferrini, F. & De Koninck, Y. Microglia control neuronal network excitability via BDNF signalling. Neural Plast.2013, 429815 (2013).
pubmed: 24089642
pmcid: 3780625
Rivera, C. et al. Mechanism of activity-dependent downregulation of the neuron-specific K-Cl cotransporter KCC2. J. Neurosci.24, 4683–4691 (2004).
pubmed: 15140939
pmcid: 6729393
Belenky, M. A. et al. Cell-type specific distribution of chloride transporters in the rat suprachiasmatic nucleus. Neuroscience165, 1519–1537 (2010).
pubmed: 19932740
Choi, H. J. et al. Excitatory actions of GABA in the suprachiasmatic nucleus. J. Neurosci.28, 5450–5459 (2008).
pubmed: 18495878
pmcid: 2570697
Glykys, J. et al. Local impermeant anions establish the neuronal chloride concentration. Science343, 670–675 (2014).
pubmed: 24503855
pmcid: 4220679
Gulacsi, A. et al. Cell type-specific differences in chloride-regulatory mechanisms and GABA(A) receptor-mediated inhibition in rat substantia nigra. J. Neurosci.23, 8237–8246 (2003).
pubmed: 12967985
pmcid: 6740695
Doyon, N. et al. Efficacy of synaptic inhibition depends on multiple, dynamically interacting mechanisms implicated in chloride homeostasis. PLoS Comput. Biol.7, e1002149 (2011).
pubmed: 21931544
pmcid: 3169517
Doyon, N., Prescott, S. A. & De Koninck, Y. Mild KCC2 hypofunction causes inconspicuous chloride dysregulation that degrades neural coding. Front. Cell. Neurosci.9, 516 (2015).
pubmed: 26858607
Prescott, S. A., Sejnowski, T. J. & De Koninck, Y. Reduction of anion reversal potential subverts the inhibitory control of firing rate in spinal lamina I neurons: towards a biophysical basis for neuropathic pain. Mol. Pain2, 32 (2006).
Kaila, K., Ruusuvuori, E., Seja, P., Voipio, J. & Puskarjov, M. GABA actions and ionic plasticity in epilepsy. Curr. Opin. Neurobiol.26, 34–41 (2014).
pubmed: 24650502
Huang, Y. J. & Grau, J. W. Ionic plasticity and pain: The loss of descending serotonergic fibers after spinal cord injury transforms how GABA affects pain. Exp. Neurol.306, 105–116 (2018).
pubmed: 29729247
pmcid: 5994379
Ormond, J. & Woodin, M. A. Disinhibition-mediated LTP in the hippocampus is synapse specific. Front. Cell. Neurosci. 5, 17 (2011).
Wang, W., Wang, H., Gong, N. & Xu, T. L. Changes of K+ -Cl- cotransporter 2 (KCC2) and circuit activity in propofol-induced impairment of long-term potentiation in rat hippocampal slices. Brain Res. Bull.70, 444–449 (2006).
pubmed: 17027780
Todd, A. J. Neuronal circuitry for pain processing in the dorsal horn. Nat. Rev. Neurosci.11, 823–836 (2010).
pubmed: 21068766
pmcid: 3277941
Cordero-Erausquin, M., Coull, J. A. M., Boudreau, D., Rolland, M. & De Koninck, Y. Differential maturation of GABA action and anion reversal potential in spinal lamina I neurons: Impact of chloride extrusion capacity. J. Neurosci.25, 9613–9623 (2005).
pubmed: 16237166
pmcid: 6725724
DeFazio, R. A., Keros, S., Quick, M. W. & Hablitz, J. J. Potassium-coupled chloride cotransport controls intracellular chloride in rat neocortical pyramidal neurons. J. Neurosci.20, 8069–8076 (2000).
pubmed: 11050128
pmcid: 6772739
Martina, M., Royer, S. & Pare, D. Cell-type-specific GABA responses and chloride homeostasis in the cortex and amygdala. J. Neurophysiol.86, 2887–2895 (2001).
pubmed: 11731545
Balena, T. & Woodin, M. A. Coincident pre- and postsynaptic activity downregulates NKCC1 to hyperpolarize E-Cl during development. Eur. J. Neurosci.27, 2402–2412 (2008).
pubmed: 18430034
Kyrozis, A. & Reichling, D. B. Perforated-patch recording with gramicidin avoids artifactual changes in intracellular chloride concentration. J. Neurosci. Meth.57, 27–35 (1995).
Staley, K. J. & Proctor, W. R. Modulation of mammalian dendritic GABA(A) receptor function by the kinetics of Cl- and HCO3- transport. J. Physiol.519(Pt 3), 693–712 (1999).
pubmed: 10457084
pmcid: 2269533
Chery, N. & De Koninck, Y. Junctional versus extrajunctional glycine and GABA(A) receptor-mediated IPSCs in identified lamina I neurons of the adult rat spinal cord. J. Neurosci.19, 7342–7355 (1999).
pubmed: 10460241
pmcid: 6782499
Littlewood, N. K., Todd, A. J., Spike, R. C., Watt, C. & Shehab, S. A. S. The types of neuron in spinal dorsal horn which possess neurokinin-1 receptors. Neuroscience66, 597–608 (1995).
pubmed: 7543982
Lorenzo, L. E., Ramien, M., Louis, M. S., De Koninck, Y. & Ribeiro-Da-Silva, A. Postnatal changes in the Rexed lamination and markers of nociceptive afferents in the superficial dorsal horn of the rat. J. Comp. Neurol.508, 592–604 (2008).
pubmed: 18383051
Polgar, E., Fowler, J. H., McGill, M. M. & Todd, A. J. The types of neuron which contain protein kinase C gamma in rat spinal cord. Brain Res.833, 71–80 (1999).
pubmed: 10375678
Ferrini, F., Salio, C., Vergnano, A. M. & Merighi, A. Vanilloid receptor-1 (TRPV 1)-dependent activation of inhibitory neurotransmission in spinal substantia gelatinosa neurons of mouse. Pain129, 195–209 (2007).
pubmed: 17317009
Funai, Y. et al. Systemic dexmedetomidine augments inhibitory synaptic transmission in the superficial dorsal horn through activation of descending noradrenergic control: an in vivo patch-clamp analysis of analgesic mechanisms. Pain155, 617–628 (2014).
pubmed: 24355412
Perez-Sanchez, J. & Koninck, Y. D. Regulation of Chloride Gradients and Neural Plasticity (Oxford University Press, 2019).
Dedek, A. et al. Loss of STEP61 couples disinhibition to N-methyl-d-aspartate receptor potentiation in rodent and human spinal pain processing. Brain142, 1535–1546 (2019).
pubmed: 31135041
pmcid: 6536915
Ferrini, F., Lorenzo, L. E., Godin, A. G., Quang, M. L. & De Koninck, Y. Enhancing KCC2 function counteracts morphine-induced hyperalgesia. Sci. Rep.7, 3870 (2017).
pubmed: 28634406
pmcid: 5478677
Lorenzo, L. E. et al. Enhancing neuronal chloride extrusion rescues alpha2/alpha3 GABAA-mediated analgesia in neuropathic pain. Nat. Commun.11, 869 (2020).
pubmed: 32054836
pmcid: 7018745
Salio, C., Lossi, L., Ferrini, F. & Merighi, A. Ultrastructural evidence for a pre- and postsynaptic localization of full-length trkB receptors in substantia gelatinosa (lamina II) of rat and mouse spinal cord. Eur. J. Neurosci.22, 1951–1966 (2005).
pubmed: 16262634
Cazorla, M. et al. Identification of a low-molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice. J. Clin. Invest.121, 1846–1857 (2011).
pubmed: 21505263
pmcid: 3083767
Barbeau, A. et al. Quantification of receptor tyrosine kinase activation and transactivation by G-protein-coupled receptors using spatial intensity distribution analysis (SpIDA). Methods Enzymol.522, 109–131 (2013).
pubmed: 23374183
Godin, A. G. et al. Revealing protein oligomerization and densities in situ using spatial intensity distribution analysis. Proc. Natl Acad. Sci. USA108, 7010–7015 (2011).
pubmed: 21482753
Swift, J. L. et al. Quantification of receptor tyrosine kinase transactivation through direct dimerization and surface density measurements in single cells. Proc. Natl Acad. Sci. USA108, 7016–7021 (2011).
pubmed: 21482778
Ruusuvuori, E. et al. Neuronal carbonic anhydrase VII provides GABAergic excitatory drive to exacerbate febrile seizures. EMBO J.32, 2275–2286 (2013).
pubmed: 23881097
pmcid: 3746197
Staley, K. J., Soldo, B. L. & Proctor, W. R. Ionic mechanisms of neuronal excitation by inhibitory gaba(A) receptors. Science269, 977–981 (1995).
pubmed: 7638623
Chery, N. & De Koninck, Y. GABA(B) receptors are the first target of released GABA at lamina I inhibitory synapses in the adult rat spinal cord. J. Neurophysiol.84, 1006–1011 (2000).
pubmed: 10938323
Keller, A. F., Coull, J. A., Chery, N., Poisbeau, P. & De Koninck, Y. Region-specific developmental specialization of GABA-glycine cosynapses in laminas I-II of the rat spinal dorsal horn. J. Neurosci.21, 7871–7880 (2001).
pubmed: 11588160
pmcid: 6763841
Ferando, I., Faas, G. C. & Mody, I. Diminished KCC2 confounds synapse specificity of LTP during senescence. Nat. Neurosci.19, 1197–1200 (2016).
pubmed: 27500406
pmcid: 5003660
Bonin, R. P. & De Koninck, Y. A spinal analog of memory reconsolidation enables reversal of hyperalgesia. Nat. Neurosci.17, 1043–1045 (2014).
pubmed: 24997764
pmcid: 4978538
Ikeda, H. et al. Synaptic amplifier of inflammatory pain in the spinal dorsal horn. Science312, 1659–1662 (2006).
pubmed: 16778058
De Koninck, Y. & Henry, J. L. Prolonged GABAA-mediated inhibition following single hair afferent input to single spinal dorsal horn neurones in cats. J. Physiol.476, 89–100 (1994).
pubmed: 8046637
pmcid: 1160421
Lorenzo, L. E. et al. Gephyrin clusters are absent from small diameter primary afferent terminals despite the presence of GABA(A) receptors. J. Neurosci.34, 8300–8317 (2014).
pubmed: 24920633
pmcid: 6608243
Cavanaugh, D. J. et al. Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli. Proc. Natl Acad. Sci. USA106, 9075–9080 (2009).
pubmed: 19451647
Ribeiro-da-Silva, A. & De Koninck, Y. in The Science of Pain (eds Bushnell, M. C. & Basbaum, A. I.) 279–310 (Academic Press, New York, 2009).
Zylka, M. J., Rice, F. L. & Anderson, D. J. Topographically distinct epidermal nociceptive circuits revealed by axonal tracers targeted to Mrgprd. Neuron45, 17–25 (2005).
pubmed: 15629699
Daou, I. et al. Remote optogenetic activation and sensitization of pain pathways in freely moving mice. J. Neurosci.33, 18631–18640 (2013).
pubmed: 24259584
pmcid: 6618811
Cavanaugh, D. J. et al. Restriction of transient receptor potential vanilloid-1 to the peptidergic subset of primary afferent neurons follows its developmental downregulation in nonpeptidergic neurons. J. Neurosci.31, 10119–10127 (2011).
pubmed: 21752988
pmcid: 3147010
Bonin, R. P., et al. Epidural optogenetics for controlled analgesia. Mol. Pain12, 1744806916629051 (2016).
Kaila, K., Price, T. J., Payne, J. A., Puskarjov, M. & Voipio, J. Cation-chloride cotransporters in neuronal development, plasticity and disease. Nat. Rev. Neurosci.15, 637–654 (2014).
pubmed: 25234263
pmcid: 4294553
Khirug, S. et al. Distinct properties of functional KCC2 expression in immature mouse hippocampal neurons in culture and in acute slices. Eur. J. Neurosci.21, 899–904 (2005).
pubmed: 15787696
Merighi, A. et al. BDNF as a pain modulator. Prog. Neurobiol.85, 297–317 (2008).
pubmed: 18514997
Minichiello, L. TrkB signalling pathways in LTP and learning. Nat. Rev. Neurosci.10, 850–860 (2009).
pubmed: 19927149
Grau, J. W. & Huang, Y. J. Metaplasticity within the spinal cord: evidence brain-derived neurotrophic factor (BDNF), tumor necrosis factor (TNF), and alterations in GABA function (ionic plasticity) modulate pain and the capacity to learn. Neurobiol. Learn. Mem.154, 121–135 (2018).
pubmed: 29635030
pmcid: 6139037
Hildebrand, M. E. et al. Potentiation of synaptic GluN2B NMDAR currents by Fyn kinase is gated through BDNF-mediated disinhibition in spinal pain processing. Cell Rep.17, 2753–2765 (2016).
pubmed: 27926876
De Koninck, Y. & Henry, J. L. Substance P-mediated slow excitatory postsynaptic potential elicited in dorsal horn neurons in vivo by noxious stimulation. Proc. Natl Acad. Sci. USA88, 11344–11348 (1991).
pubmed: 1722327
Sandkuhler, J. & Gruber-Schoffnegger, D. Hyperalgesia by synaptic long-term potentiation (LTP): an update. Curr. Opin. Pharmacol.12, 18–27 (2012).
pubmed: 22078436
pmcid: 3315008
Sanchez-Brualla, I. et al. Activation of 5-HT2A receptors restores KCC2 function and reduces neuropathic pain after spinal cord injury. Neuroscience387, 48–57 (2018).
pubmed: 28844001
Salio, C., Averill, S., Priestley, J. V. & Merighi, A. Costorage of BDNF and neuropeptides within individual dense-core vesicles in central and peripheral neurons. Dev. Neurobiol.67, 326–338 (2007).
pubmed: 17443791
Li, L. et al. Chloride homeostasis critically regulates synaptic NMDA receptor activity in neuropathic pain. Cell Rep.15, 1376–1383 (2016).
pubmed: 27160909
pmcid: 4871741
Abraira, V. E. et al. The cellular and synaptic architecture of the mechanosensory dorsal horn. Cell168, 295–310 e219 (2017).
pubmed: 28041852
pmcid: 5236062
Roberts, L. A., Beyer, C. & Komisaruk, B. R. Nociceptive responses to altered GABAergic activity at the spinal cord. Life Sci.39, 1667–1674 (1986).
pubmed: 3022091
Yaksh, T. L. Behavioral and autonomic correlates of the tactile evoked allodynia produced by spinal glycine inhibition: effects of modulatory receptor systems and excitatory amino acid antagonists. Pain37, 111–123 (1989).
pubmed: 2542867
Lee, K. Y., Ratte, S. & Prescott, S. A. Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn. eLife8, e49753 (2019).
Lu, Y., Zheng, J., Xiong, L., Zimmermann, M. & Yang, J. Spinal cord injury-induced attenuation of GABAergic inhibition in spinal dorsal horn circuits is associated with down-regulation of the chloride transporter KCC2 in rat. J. Physiol.586, 5701–5715 (2008).
pubmed: 18845615
pmcid: 2655400
Costigan, M., Scholz, J. & Woolf, C. J. Neuropathic pain: a maladaptive response of the nervous system to damage. Annu. Rev. Neurosci.32, 1–32 (2009).
pubmed: 19400724
pmcid: 2768555
Kaila, K. Ionic basis of Gaba(A) receptor-channel function in the nervous-system. Prog. Neurobiol.42, 489–537 (1994).
pubmed: 7522334
Mercado, A., Broumand, V., Zandi-Nejad, K., Enck, A. H. & Mount, D. B. A C-terminal domain in KCC2 confers constitutive K+-Cl- cotransport. J. Biol. Chem.281, 1016–1026 (2006).
pubmed: 16291749
Williams, J. R., Sharp, J. W., Kumari, V. G., Wilson, M. & Payne, J. A. The neuron-specific K-Cl cotransporter, KCC2. J. Biol. Chem.274, 12656–12664 (1999).
pubmed: 10212246
Patrizio, A. & Specht, C. G. Counting numbers of synaptic proteins: absolute quantification and single molecule imaging techniques. Neurophotonics3, 041805 (2016).
pubmed: 27335891
pmcid: 4891561
Sugiyama, Y., Kawabata, I., Sobue, K. & Okabe, S. Determination of absolute protein numbers in single synapses by a GFP-based calibration technique. Nat. Methods2, 677–684 (2005).
pubmed: 16118638
Verdaasdonk, J. S., Lawrimore, J. & Bloom, K. Determining absolute protein numbers by quantitative fluorescence microscopy. Methods Cell Biol.123, 347–365 (2014).
pubmed: 24974037
pmcid: 4221264
Durisic, N. et al. Stoichiometry of the human glycine receptor revealed by direct subunit counting. J. Neurosci.32, 12915–12920 (2012).
pubmed: 22973015
pmcid: 3475605
Godin, A. G. et al. Spatial intensity distribution analysis reveals abnormal oligomerization of proteins in single cells. Biophys. J.109, 710–721 (2015).
pubmed: 26287623
pmcid: 4547338
Ulbrich, M. H. & Isacoff, E. Y. Subunit counting in membrane-bound proteins. Nat. Methods4, 319–321 (2007).
pubmed: 17369835
pmcid: 2744285
Ribeiro-Da-Silva, A. Substantia gelatinosa of spinal cord. in The Rat Nervous System (ed. Paxinos, G.) 129–148 (Academic Press, New York, 2004).
Chen, M., et al. APP modulates KCC2 expression and function in hippocampal GABAergic inhibition. eLife6, e20142 (2017).
Lizhnyak, P. N., Muldoon, P. P., Pilaka, P. P., Povlishock, J. T. & Ottens, A. K. Traumatic brain injury temporal proteome guides KCC2-targeted therapy. J. Neurotrauma36, 3092–3102 (2019).
pubmed: 31122143
Bonin, R. P., Bories, C. & De Koninck, Y. A simplified up-down method (SUDO) for measuring mechanical nociception in rodents using von Frey filaments. Mol. Pain.10, 26 (2014).
pubmed: 24739328
pmcid: 4020614
Hille, B. Ion Channels of Excitable Membranes, (Sinauer, Sunderalnd, MA, 2001).
Geiger, J. R., Lubke, J., Roth, A., Frotscher, M. & Jonas, P. Submillisecond AMPA receptor-mediated signaling at a principal neuron-interneuron synapse. Neuron18, 1009–1023 (1997).
pubmed: 9208867
Eyre, M. D., Renzi, M., Farrant, M. & Nusser, Z. Setting the time course of inhibitory synaptic currents by mixing multiple GABA(A) receptor alpha subunit isoforms. J. Neurosci.32, 5853–5867 (2012).
pubmed: 22539847
pmcid: 3348502
Williams, S. R. Spatial compartmentalization and functional impact of conductance in pyramidal neurons. Nat. Neurosci.7, 961–967 (2004).
pubmed: 15322550
Frohlich, F., Bazhenov, M., Iragui-Madoz, V. & Sejnowski, T. J. Potassium dynamics in the epileptic cortex: new insights on an old topic. Neuroscientist14, 422–433 (2008).
pubmed: 18997121
pmcid: 2854295