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Pharmacopsychiatry 2010; 43: S21-S31
DOI: 10.1055/s-0030-1253376
Review

© Georg Thieme Verlag KG Stuttgart · New York

No Simple Brake – the Complex Functions of Inhibitory Synapses

G. Birke1 , A. Draguhn1
  • 1Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany
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Publication History

Publication Date:
17 May 2010 (online)

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Abstract

Synaptic inhibition can be viewed as a counterbalance of synaptic excitation. However, mul-tiple recent studies at the cellular and network level show that inhibition serves a variety of additional, highly specific functions in the mammalian nervous system. At the molecular and cellular level, inhibitory synapses express diverse postsynaptic reversal potentials, kinetics, plasticity, and pharmacological modulation. This heterogeneity corresponds to the complexity of inhibition at the network level, where interneurons are now perceived as diverse and highly specific organizers of coherent activity patterns. We review some important new developments in the molecular, cellular and network physiology of inhibition. It turns out that understanding inhibition is a key to understanding neuronal network behaviour and, ultimately, may provide important clues for the development of novel therapeutic strategies in neuro-psychiatric diseases.

References

  • 1 Alle H, Geiger JR. GABAergic spill-over transmission onto hippocampal mossy fiber boutons.  J Neurosci. 2007;  27 (4) 942-950
    CrossrefPubMedGoogle Scholar
  • 2 Ascoli GA, onso-Nanclares L, Anderson SA. et al . Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex.  Nat Rev Neurosci. 2008;  9 (7) 557-568
    CrossrefPubMedGoogle Scholar
  • 3 Axmacher N, Stemmler M, Engel D. et al . Transmitter metabolism as a mechanism of synaptic plasticity: a modeling study.  J Neurophysiol. 2004;  91 (1) 25-39
    CrossrefPubMedGoogle Scholar
  • 4 Bak LK, Schousboe A, Waagepetersen HS. The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer.  J Neurochem. 2006;  98 (3) 641-653
    CrossrefPubMedGoogle Scholar
  • 5 Banks MI, Pearce RA. Kinetic differences between synaptic and extrasynaptic GABAA receptors in CA1 pyramidal cells.  J Neurosci. 2000;  20 (3) 937-948
    PubMedGoogle Scholar
  • 6 Bartos M, Vida I, Frotscher M. et al . Rapid signaling at inhibitory synapses in a dentate gyrus interneuron network.  J Neurosci. 2001;  21 (8) 2687-2698
    PubMedGoogle Scholar
  • 7 Bartos M, Vida I, Frotscher M. et al . Fast synaptic inhibition promotes synchronized gamma oscillations in hippocampal interneuron networks.  Proc Natl Acad Sci USA. 2002;  99 (20) 13222-13227
    CrossrefPubMedGoogle Scholar
  • 8 Beau FEN, Alger BE. Transient suppression of GABAA-receptor-mediated IPSPs after epileptiform burst discharges in CA1 pyramidal cells.  J Neurophysiol. 1998;  79 (2) 659-669
    PubMedGoogle Scholar
  • 9 Ben-Ari Y. Excitatory actions of GABA during development: the nature of the nurture.  Nat Rev Neurosci. 2002;  3 (9) 728-739
    CrossrefPubMedGoogle Scholar
  • 10 Ben-Ari Y, Cherubini E, Corradetti R. et al . Giant synaptic potentials in immature rat CA3 hippocampal neurones.  J Physiol. 1989;  416 303-325
    PubMedGoogle Scholar
  • 11 Ben-Ari Y, Tseeb V, Raggozzino D. et al . Gamma-aminobutyric acid (GABA): a fast excitatory transmitter which may regulate the development of hippocampal neurones in early postnatal life.  Prog Brain Res. 1994;  102 261-273
    PubMedGoogle Scholar
  • 12 Blaesse P, Airaksinen MS, Rivera C. et al . Cation-chloride cotransporters and neuronal function.  Neuron. 2009;  61 (6) 820-838
    CrossrefPubMedGoogle Scholar
  • 13 Bormann J, Feigenspan A. GABAC receptors.  Trends Neurosci. 1995;  18 (12) 515-519
    CrossrefPubMedGoogle Scholar
  • 14 Bormann J, Hamill OP, Sakmann B. Mechanism of anion permeation through channels gated by glycine and γ-aminobutyric acid in mouse cultured spinal neurones.  J Physiol. 1987;  385 243-286
    PubMedGoogle Scholar
  • 15 Bouilleret V, Loup F, Kiener T. et al . Early loss of interneurons and delayed subunit-specific changes in GABAA-receptor expression in a mouse model of mesial temporal lobe epilepsy.  Hippocampus. 2000;  10 (3) 305-324
    CrossrefPubMedGoogle Scholar
  • 16 Brickley SG, Revilla V, Cull-Candy SG. et al . Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance.  Nature. 2001;  409 (6816) 88-92
    CrossrefPubMedGoogle Scholar
  • 17 Buhl EH, Otis TS, Mody I. Zinc-induced collapse of augmented inhibition by GABA in a temporal lobe epilepsy model.  Science. 1996;  271 (5247) 369-373
    CrossrefPubMedGoogle Scholar
  • 18 Buzsaki G, Csicsvari J, Dragoi G. et al . Homeostatic maintenance of neuronal excitability by burst discharges in vivo.  Cereb Cortex. 2002;  12 (9) 893-899
    CrossrefPubMedGoogle Scholar
  • 19 Buzsáki G, Draguhn A. Neuronal oscillations in cortical networks.  Science. 2004;  304 (5679) 1926-1929
    CrossrefPubMedGoogle Scholar
  • 20 Caraiscos VB, Elliott EM, You-Ten KE. et al . Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by α5 subunit-containing γ-aminobutyric acid type A receptors.  Proc Natl Acad Sci USA. 2004;  101 (10) 3662-3667
    CrossrefPubMedGoogle Scholar
  • 21 Cavelier P, Hamann M, Rossi D. et al . Tonic excitation and inhibition of neurons: ambient transmitter sources and computational consequences.  Prog Biophys Mol Biol. 2005;  87 (1) 3-16
    CrossrefPubMedGoogle Scholar
  • 22 Cohen I, Navarro V, Clemenceau S. et al . On the origin of interictal activity in human temporal lobe epilepsy in vitro.  Science. 2002;  298 (5597) 1418-1421
    CrossrefPubMedGoogle Scholar
  • 23 Conti F, DeBiasi S, Minelli A. et al . EAAC1, a high-affinity glutamate tranporter, is localized to astrocytes and gabaergic neurons besides pyramidal cells in the rat cerebral cortex.  Cereb Cortex. 1998;  8 (2) 108-116
    CrossrefPubMedGoogle Scholar
  • 24 Cossart R, Dinocourt C, Hirsch JC. et al . Dendritic but not somatic GABAergic inhibition is decreased in experimental epilepsy.  Nat Neurosci. 2001;  4 (1) 52-62
    CrossrefPubMedGoogle Scholar
  • 25 Coulter DA. Epilepsy-associated plasticity in γ-aminobutyric acid receptor expression, function, and inhibitory synaptic properties.  Int Rev Neurobiol. 2001;  45 237-252
    PubMedGoogle Scholar
  • 26 De Gois S, Schäfer MKH, Defamie N. et al . Homeostatic scaling of vesicular glutamate and GABA transporter expression in rat neocortical circuits.  J Neurosci. 2005;  25 (31) 7121-7133
    CrossrefPubMedGoogle Scholar
  • 27 Draguhn A, Axmacher N, Kolbaev S. Presynaptic ionotropic GABA receptors.  Results Probl Cell Differ. 2008;  44 69-85
    PubMedGoogle Scholar
  • 28 Durstewitz D, Deco G. Computational significance of transient dynamics in cortical networks.  Eur J Neurosci. 2008;  27 (1) 217-227
    CrossrefPubMedGoogle Scholar
  • 29 Durstewitz D, Seamans JK. The dual-state theory of prefrontal cortex dopamine function with relevance to catechol-o-methyltransferase genotypes and schizophrenia.  Biol Psychiatry. 2008;  64 (9) 739-749
    CrossrefPubMedGoogle Scholar
  • 30 Eccles JC, Schmidt RF, Willis WD. Presynaptic inhibition of the spinal monosynaptic reflex pathway.  J Physiol. 1962;  161 282-297
    PubMedGoogle Scholar
  • 31 Engel D, Pahner I, Schulze K. et al . Plasticity of rat central inhibitory synapses through GABA metabolism.  J Physiol. 2001;  535 (2) 473-482
    CrossrefPubMedGoogle Scholar
  • 32 Erickson JD, De Gois S, Varoqui H. et al . Activity-dependent regulation of vesicular glutamate and GABA transporters: a means to scale quantal size.  Neurochem Int. 2006;  48 (6–7) 643-649
    PubMedGoogle Scholar
  • 33 Esclapez M, Houser CR. Up-regulation of GAD65 and GAD67 in remaining hippocampal GABA neurons in a model of temporal lobe epilepsy.  J Comp Neurol. 1999;  412 (3) 488-505
    CrossrefPubMedGoogle Scholar
  • 34 Farrant M, Nusser Z. Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors.  Nat Rev Neurosci. 2005;  6 (3) 215-229
    CrossrefPubMedGoogle Scholar
  • 35 Feldblum S, Ackermann RF, Tobin AJ. Long-term increase of glutamate decarboxylase mRNA in a rat model of temporal lobe epilepsy.  Neuron. 1990;  5 (3) 361-371
    CrossrefPubMedGoogle Scholar
  • 36 Freund TF, Buzsaki G. Interneurons of the hippocampus.  Hippocampus. 1996;  6 (4) 347-470
    CrossrefPubMedGoogle Scholar
  • 37 Fricke MN, Jones-Davis DM, Mathews GC. Glutamine uptake by System A transporters maintains neurotransmitter GABA synthesis and inhibitory synaptic transmission.  J Neurochem. 2007;  102 (6) 1895-1904
    CrossrefPubMedGoogle Scholar
  • 38 Fritschy J-M. Epilepsy, E/I balance and GABAA receptor plasticity.  Front Mol Neurosci. 2008;  1 (article 5)
    PubMedGoogle Scholar
  • 39 Gabriel S, Njunting M, Pomper JK. et al . Stimulus and potassium-induced epileptiform activity in the human dentate gyrus from patients with and without hippocampal sclerosis.  J Neurosci. 2004;  24 (46) 10416-10430
    CrossrefPubMedGoogle Scholar
  • 40 Garraghty PE, Lachica EA, Kaas JH. Injury-induced reorganization of somatosensory cortex is accompanied by reductions in GABA staining.  Somatosens Mot Res. 1991;  8 (4) 347-354
    CrossrefPubMedGoogle Scholar
  • 41 Glickfeld LL, Roberts JD, Somogyi P. et al . Interneurons hyperpolarize pyramidal cells along their entire somatodendritic axis.  Nat Neurosci. 2009;  12 (1) 21-23
    CrossrefPubMedGoogle Scholar
  • 42 Glykys J, Mann EO, Mody I. Which GABAA receptor subunits are necessary for tonic inhibition in the hippocampus?.  J Neurosci. 2008;  28 (6) 1421-1426
    CrossrefPubMedGoogle Scholar
  • 43 Glykys J, Mody I. The main source of ambient GABA responsible for tonic inhibition in the mouse hippocampus.  J Physiol. 2007;  582 (3) 1163-1178
    CrossrefPubMedGoogle Scholar
  • 44 Grewe BF, Helmchen F. Optical probing of neuronal ensemble activity.  Curr Opin Neurobiol. 2009;  19 (5) 520-529
    CrossrefPubMedGoogle Scholar
  • 45 Gulledge AT, Stuart GJ. Excitatory actions of GABA in the cortex.  Neuron. 2003;  37 (2) 299-309
    CrossrefPubMedGoogle Scholar
  • 46 Hartmann K, Bruehl C, Golovko T. et al . Fast homeostatic plasticity of inhibition via activity-dependent vesicular filling.  PLoS One. 2008;  3 (8) e2979
    CrossrefPubMedGoogle Scholar
  • 47 Hevers W, Lüddens H. The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes.  Mol Neurobiol. 1998;  18 (1) 35-86
    CrossrefPubMedGoogle Scholar
  • 48 Holmgren CD, Mukhtarov M, Malkov AE. et al . Energy substrate availability as a determinant of neuronal resting potential, GABA signaling and spontaneous network activity in the neonatal cortex in vitro.  J Neurochem. 2009; 
    PubMedGoogle Scholar
  • 49 Jin H, Wu H, Osterhaus G. et al . Demonstration of functional coupling between γ-aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles.  Proc Natl Acad Sci USA. 2003;  100 (7) 4293-4298
    CrossrefPubMedGoogle Scholar
  • 50 Jinno S, Klausberger T, Marton LF. et al . Neuronal diversity in GABAergic long-range projections from the hippocampus.  J Neurosci. 2007;  27 (33) 8790-8804
    CrossrefPubMedGoogle Scholar
  • 51 Kaila K, Voipio J. Postsynaptic fall in intracellular pH induced by GABA-activated bicarbonate conductance.  Nature. 1987;  330 (6144) 163-165
    CrossrefPubMedGoogle Scholar
  • 52 Katz LC, Shatz CJ. Synaptic activity and the construction of cortical circuits.  Science. 1996;  274 (5290) 1133-1138
    CrossrefPubMedGoogle Scholar
  • 53 Klausberger T, Magill PJ, Márton LF. et al . Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo.  Nature. 2003;  421 (6925) 844-848
    CrossrefPubMedGoogle Scholar
  • 54 Klausberger T, Somogyi P. Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations.  Science. 2008;  321 (5885) 53-57
    CrossrefPubMedGoogle Scholar
  • 55 Kullmann DM, Ruiz A, Rusakov DM. et al . Presynaptic, extrasynaptic and axonal GABAA receptors in the CNS: where and why?.  Prog Biophys Mol Biol. 2005;  87 (1) 33-46
    CrossrefPubMedGoogle Scholar
  • 56 Lamsa K, Heeroma JH, Kullmann DM. Hebbian LTP in feed-forward inhibitory interneurons and the temporal fidelity of input discrimination.  Nat Neurosci. 2005;  8 (7) 916-924
    PubMedGoogle Scholar
  • 57 Leschinger A, Stabel J, Igelmund P. et al . Pharmacological and electrographic properties of epileptiform activity induced by elevated K+ and lowered Ca2+ and Mg2+ concentration in rat hippocampal slices.  Exp Brain Res. 1993;  96 (2) 230-240
    PubMedGoogle Scholar
  • 58 Leutgeb JK, Leutgeb S, Moser M-B. et al . Pattern separation in the dentate gyrus and CA3 of the hippocampus.  Science. 2007;  315 (5814) 961-966
    CrossrefPubMedGoogle Scholar
  • 59 Lewis DA, Sweet RA. Schizophrenia from a neural circuitry perspective: advancing toward rational pharmacological therapies.  J Clin Invest. 2009;  119 (4) 706-716
    CrossrefPubMedGoogle Scholar
  • 60 Liang S-L, Carlson GC, Coulter DA. Dynamic regulation of synaptic GABA release by the glutamate-glutamine cycle in hippocampal area CA1.  J Neurosci. 2006;  26 (33) 8537-8548
    CrossrefPubMedGoogle Scholar
  • 61 Lin L, Osan R, Shoham S. et al . Identification of network-level coding units for real-time representation of episodic experiences in the hippocampus.  Proc Natl Acad Sci USA. 2005;  102 (17) 6125-6130
    CrossrefPubMedGoogle Scholar
  • 62 Lisman JE, Coyle JT, Green RW. et al . Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia.  Trends Neurosci. 2008;  31 (5) 234-242
    CrossrefPubMedGoogle Scholar
  • 63 Logothetis NK, Pauls J, Augath M. et al . Neurophysiological investigation of the basis of the fMRI signal.  Nature. 2001;  412 (6843) 150-157
    CrossrefPubMedGoogle Scholar
  • 64 Mann EO, Paulsen O. Role of GABAergic inhibition in hippocampal network oscillations.  Trends Neurosci. 2007;  30 (7) 343-349
    CrossrefPubMedGoogle Scholar
  • 65 Mathews GC, Diamond JS. Neuronal glutamate uptake contributes to GABA synthesis and inhibitory synaptic strength.  J Neurosci. 2003;  23 (6) 2040-2048
    PubMedGoogle Scholar
  • 66 Melone M, Quagliano F, Barbaresi P. et al . Localization of the glutamine transporter SNAT1 in rat cerebral cortex and neighboring structures, with a note on its localization in human cortex.  Cereb Cortex. 2004;  14 (5) 562-574
    CrossrefPubMedGoogle Scholar
  • 67 Misgeld U, Bijak M, Jarolimek W. A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system.  Prog Neurobiol. 1995;  46 (4) 423-462
    CrossrefPubMedGoogle Scholar
  • 68 Mody I. Distinguishing between GABAA receptors responsible for tonic and phasic conductances.  Neurochem Res. 2001;  26 (8–9) 907-913
    CrossrefPubMedGoogle Scholar
  • 69 Mody I, Pearce RA. Diversity of inhibitory neurotransmission through GABAA receptors.  Trends Neurosci. 2004;  27 (9) 569-575
    CrossrefPubMedGoogle Scholar
  • 70 Morales-Aza BM, Chillingworth NL, Payne JA. et al . Inflammation alters cation chloride cotransporter expression in sensory neurons.  Neurobiol Dis. 2004;  17 (1) 62-69
    CrossrefPubMedGoogle Scholar
  • 71 Niessing J, Ebisch B, Schmidt KE. et al . Hemodynamic signals correlate tightly with synchronized gamma oscillations.  Science. 2005;  309 (5736) 948-951
    CrossrefPubMedGoogle Scholar
  • 72 Olah S, Fule M, Komlosi G. et al . Regulation of cortical microcircuits by unitary GABA-mediated volume transmission.  Nature. 2009;  461 (7268) 1278-1281
    CrossrefPubMedGoogle Scholar
  • 73 Pearce RA. Physiological evidence for two distinct GABAA responses in rat hippocampus.  Neuron. 1993;  10 (2) 189-200
    CrossrefPubMedGoogle Scholar
  • 74 Pinault D. A novel single-cell staining procedure performed in vivo under electrophysiological control: morpho-functional features of juxtacellularly labeled thalamic cells and other central neurons with biocytin or Neurobiotin.  J Neurosci Meth. 1996;  65 (2) 113-136
    CrossrefPubMedGoogle Scholar
  • 75 Qi Z, Miller GW, Voit EO. A mathematical model of presynaptic dopamine homeostasis: implications for schizophrenia.  Pharmacopsychiatry. 2008;  41 (S 01) S89-S98
    Article in Thieme ConnectPubMedGoogle Scholar
  • 76 Qi Z, Miller GW, Voit EO. Computational analysis of determinants of dopamine (DA) dysfunction in DA nerve terminals.  Synapse. 2009;  63 (12) 1133-1142
    CrossrefPubMedGoogle Scholar
  • 77 Rheims S, Holmgren CD, Chazal G. et al . GABA action in immature neocortical neurons directly depends on the availability of ketone bodies.  J Neurochem. 2009;  110 (4) 1330-1338
    CrossrefPubMedGoogle Scholar
  • 78 Rivera C, Voipio J, Payne JA. et al . The K+/Cl− co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation.  Nature. 1999;  397 (6716) 251-255
    CrossrefPubMedGoogle Scholar
  • 79 Rivera C, Voipio J, Thomas-Crusells J. et al . Mechanism of activity-dependent downregulation of the neuron-specific K-Cl cotransporter KCC2.  J Neurosci. 2004;  24 (19) 4683-4691
    CrossrefPubMedGoogle Scholar
  • 80 Rudolph U, Möhler H. Analysis of GABAA receptor function and dissection of the pharmacology of benzodiazepines and general anesthetics through mouse genetics.  Annu Rev Pharmacol Toxicol. 2004;  44 475-498
    CrossrefPubMedGoogle Scholar
  • 81 Rudolph U, Möhler H. GABA-based therapeutic approaches: GABAA receptor subtype functions.  Curr Opin Pharmacol. 2006;  6 (1) 18-23
    CrossrefPubMedGoogle Scholar
  • 82 Rudomin P, Schmidt RF. Presynaptic inhibition in the vertebrate spinal cord revisited.  Exp Brain Res. 1999;  129 (1) 1-37
    CrossrefPubMedGoogle Scholar
  • 83 Ruiz A, Fabian-Fine R, Scott R. et al . GABAA receptors at hippocampal mossy fibers.  Neuron. 2003;  39 (6) 961-973
    CrossrefPubMedGoogle Scholar
  • 84 Rupprecht R, Rammes G, Eser D. et al . Translocator protein (18 kD) as target for anxiolytics without benzodiazepine-like side effects.  Science. 2009;  325 (5939) 490-493
    CrossrefPubMedGoogle Scholar
  • 85 Schuchmann S, Schmitz D, Rivera C. et al . Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis.  Nat Med. 2006;  12 (7) 817-823
    CrossrefPubMedGoogle Scholar
  • 86 Scimemi A, Andersson A, Heeroma JH. et al . Tonic GABAA receptor-mediated currents in human brain.  Eur J Neurosci. 2006;  24 (4) 1157-1160
    CrossrefPubMedGoogle Scholar
  • 87 Seamans JK, Gorelova N, Durstewitz D. et al . Bidirectional dopamine modulation of GABAergic inhibition in prefrontal cortical pyramidal neurons.  J Neurosci. 2001;  21 (10) 3628-3638
    PubMedGoogle Scholar
  • 88 Semyanov A, Walker MC, Kullmann DM. et al . Tonically active GABAA receptors: modulating gain and maintaining the tone.  Trends Neurosci. 2004;  27 (5) 262-269
    CrossrefPubMedGoogle Scholar
  • 89 Shu Y, Hasenstaub A, McCormick DA. Turning on and off recurrent balanced cortical activity.  Nature. 2003;  423 (6937) 288-293
    CrossrefPubMedGoogle Scholar
  • 90 Somogyi P, Klausberger T. Defined types of cortical interneurone structure space and spike timing in the hippocampus.  J Physiol. 2005;  562 (1) 9-26
    PubMedGoogle Scholar
  • 91 Staley KJ, Proctor WR. Modulation of mammalian dendritic GABAA receptor function by the kinetics of Cl− and HCO3 − transport.  J Physiol. 1999;  519 (3) 693-712
    CrossrefPubMedGoogle Scholar
  • 92 Staley KJ, Soldo BL, Proctor WR. Ionic mechanisms of neuronal excitation by inhibitory GABAA receptors.  Science. 1995;  269 (5226) 977-981
    CrossrefPubMedGoogle Scholar
  • 93 Stein V, Hermans-Borgmeyer I, Jentsch TJ. et al . Expression of the KCl cotransporter KCC2 parallels neuronal maturation and the emergence of low intracellular chloride.  J Comp Neurol. 2004;  468 (1) 57-64
    CrossrefPubMedGoogle Scholar
  • 94 Sung K-W, Kirby M, McDonald MP. et al . Abnormal GABAA receptor-mediated currents in dorsal root ganglion neurons isolated from Na-K-2Cl cotransporter null mice.  J Neurosci. 2000;  20 (20) 7531-7538
    PubMedGoogle Scholar
  • 95 Szabadics J, Varga C, Molnar G. et al . Excitatory effect of GABAergic axo-axonic cells in cortical microcircuits.  Science. 2006;  311 (5758) 233-235
    CrossrefPubMedGoogle Scholar
  • 96 Traub RD, Bibbig A, LeBeau FEN. et al . Cellular mechanisms of neuronal population oscillations in the hippocampus in vitro.  Annu Rev Neurosci. 2004;  27 247-278
    CrossrefPubMedGoogle Scholar
  • 97 Traub RD, Wong RKS. Cellular mechanism of neuronal synchronization in epilepsy.  Science. 1982;  216 (4547) 745-747
    CrossrefPubMedGoogle Scholar
  • 98 Tretter F, Albus M. Systems biology and psychiatry – modeling molecular and cellular networks of mental disorders.  Pharmacopsychiatry. 2008;  41 (S 01) S2-S18
    Article in Thieme ConnectPubMedGoogle Scholar
  • 99 Turrigiano GG. Homeostatic plasticity in neuronal networks: the more things change, the more they stay the same.  Trends Neurosci. 1999;  22 (5) 221-227
    CrossrefPubMedGoogle Scholar
  • 100 Turrigiano GG, Nelson SB. Hebb and homeostasis in neuronal plasticity.  Curr Opin Neurobiol. 2000;  10 (3) 358-364
    CrossrefPubMedGoogle Scholar
  • 101 Whittington MA, Traub RD. Interneuron Diversity series: inhibitory interneurons and network oscillations in vitro.  Trends Neurosci. 2003;  26 (12) 676-682
    CrossrefPubMedGoogle Scholar
  • 102 Whittington MA, Traub RD, Kopell N. et al . Inhibition-based rhythms: experimental and mathematical observations on network dynamics.  Int J Psychophysiol. 2000;  38 (3) 315-336
    CrossrefPubMedGoogle Scholar
  • 103 Wilson RI, Kunos G, Nicoll RA. Presynaptic specificity of endocannabinoid signaling in the hippocampus.  Neuron. 2001;  31 (3) 453-462
    CrossrefPubMedGoogle Scholar
  • 104 Wilson RI, Nicoll RA. Endocannabinoid signaling in the brain.  Science. 2002;  296 (5568) 678-682
    CrossrefPubMedGoogle Scholar
  • 105 Wilson RI, Nicoll RA. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses.  Nature. 2001;  410 (6828) 588-592
    CrossrefPubMedGoogle Scholar
  • 106 Woo TU, Whitehead RE, Melchitzky DS. et al . A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia.  Proc Natl Acad Sci USA. 1998;  95 (9) 5341-5346
    CrossrefPubMedGoogle Scholar
  • 107 Woo TU, Whitehead RE, Melchitzky DS. et al . A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia.  Proc Natl Acad Sci USA. 1998;  95 (9) 5341-5346
    CrossrefPubMedGoogle Scholar
  • 108 Woodruff A, Xu Q, Anderson SA. et al . Depolarizing effect of neocortical chandelier neurons.  Front Neural Circuits. 2009;  3 15
    PubMedGoogle Scholar
  • 109 Yamada J, Khirug S, Voipio L. et al . The GABAergic depolarization of the axon initial segment in cortical principal neurons is mediated by the Na-K-2Cl cotransporter NKCC1.  The Society for Neuroscience Abstracts. 2007;  683.6/G48
    CrossrefPubMedGoogle Scholar
  • 110 Zhang Z, Sun J, Reynolds GP. A selective reduction in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia patients.  Chin Med J (Engl). 2002;  115 (6) 819-823
    PubMedGoogle Scholar

Correspondence

Prof. Dr. A. Draguhn

Institute of Physiology and Pathophysiology

University of Heidelberg

Im Neuenheimer Feld 326

69120 Heidelberg

Germany

Phone: +49-6221-544056

Fax: +49-6221-546364

Email: andreas.draguhn@physiologie.uni-heidelberg.de

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