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Science 299 (5614): 1902-1905

Copyright © 2003 by the American Association for the Advancement of Science

Identified Sources and Targets of Slow Inhibition in the Neocortex

Gábor Tamás,* Andrea Lőrincz, Anna Simon, János Szabadics

There are two types of inhibitory postsynaptic potentials in the cerebral cortex. Fast inhibition is mediated by ionotropic gamma -aminobutyric acid type A (GABAA) receptors, and slow inhibition is due to metabotropic GABAB receptors. Several neuron classes elicit inhibitory postsynaptic potentials through GABAA receptors, but possible distinct sources of slow inhibition remain unknown. We identified a class of GABAergic interneurons, the neurogliaform cells, that, in contrast to other GABA-releasing cells, elicited combined GABAA and GABAB receptor-mediated responses with single action potentials and that predominantly targeted the dendritic spines of pyramidal neurons. Slow inhibition evoked by a distinct interneuron in spatially restricted postsynaptic compartments could locally and selectively modulate cortical excitability.

Department of Comparative Physiology, University of Szeged, Közép fasor 52, Szeged H-6726, Hungary.
*   To whom correspondence should be addressed. E-mail: gtamas{at}

Canonical Organization of Layer 1 Neuron-Led Cortical Inhibitory and Disinhibitory Interneuronal Circuits.
A. J. Lee, G. Wang, X. Jiang, S. M. Johnson, E. T. Hoang, F. Lante, R. L. Stornetta, M. P. Beenhakker, Y. Shen, and J. Julius Zhu (2014)
Cereb Cortex
   Abstract »    Full Text »    PDF »
Activity-Dependent Modulation of Layer 1 Inhibitory Neocortical Circuits by Acetylcholine.
A. Brombas, L. N. Fletcher, and S. R. Williams (2014)
J. Neurosci. 34, 1932-1941
   Abstract »    Full Text »    PDF »
Firing of Hippocampal Neurogliaform Cells Induces Suppression of Synaptic Inhibition.
G. Li, R. Stewart, M. Canepari, and M. Capogna (2014)
J. Neurosci. 34, 1280-1292
   Abstract »    Full Text »    PDF »
Differential GABAB-Receptor-Mediated Effects in Perisomatic- and Dendrite-Targeting Parvalbumin Interneurons.
S. A. Booker, A. Gross, D. Althof, R. Shigemoto, B. Bettler, M. Frotscher, M. Hearing, K. Wickman, M. Watanabe, A. Kulik, et al. (2013)
J. Neurosci. 33, 7961-7974
   Abstract »    Full Text »    PDF »
Novel GABAergic Circuits Mediating Excitation/Inhibition of Cajal-Retzius Cells in the Developing Hippocampus.
G. Quattrocolo and G. Maccaferri (2013)
J. Neurosci. 33, 5486-5498
   Abstract »    Full Text »    PDF »
Distinct roles of GABAB1a- and GABAB1b-containing GABAB receptors in spontaneous and evoked termination of persistent cortical activity.
M. T. Craig, E. W. Mayne, B. Bettler, O. Paulsen, and C. J. McBain (2013)
J. Physiol. 591, 835-843
   Abstract »    Full Text »    PDF »
Diversity of GABAergic Interneurons in Layer VIa and VIb of Mouse Barrel Cortex.
Q. Perrenoud, J. Rossier, H. Geoffroy, T. Vitalis, and T. Gallopin (2013)
Cereb Cortex 23, 423-441
   Abstract »    Full Text »    PDF »
A computational study of brightness-related responses in visual cortex.
B. Cao, E. Mingolla, and A. Yazdanbahksh (2013)
J Vis 13, 8
   Abstract »    Full Text »    PDF »
Mechanisms underlying long-interval cortical inhibition in the human motor cortex: a TMS-EEG study.
N. C. Rogasch, Z. J. Daskalakis, and P. B. Fitzgerald (2013)
J Neurophysiol 109, 89-98
   Abstract »    Full Text »    PDF »
Somatic and dendritic GABAB receptors regulate neuronal excitability via different mechanisms.
J.-D. Breton and G. J. Stuart (2012)
J Neurophysiol 108, 2810-2818
   Abstract »    Full Text »    PDF »
Neurogliaform cells of amygdala: a source of slow phasic inhibition in the basolateral complex.
M. Mako, T. C. M. Bienvenu, Y. Dalezios, and M. Capogna (2012)
J. Physiol. 590, 5611-5627
   Abstract »    Full Text »    PDF »
Kinetics of GABAB autoreceptor-mediated suppression of GABA release in rat insular cortex.
M. Kobayashi, H. Takei, K. Yamamoto, H. Hatanaka, and N. Koshikawa (2012)
J Neurophysiol 107, 1431-1442
   Abstract »    Full Text »    PDF »
Influence of a Subtype of Inhibitory Interneuron on Stimulus-Specific Responses in Visual Cortex.
R. Mao, J. Schummers, U. Knoblich, C. J. Lacey, A. Van Wart, I. Cobos, C. Kim, J. R. Huguenard, J. L. R. Rubenstein, and M. Sur (2012)
Cereb Cortex 22, 493-508
   Abstract »    Full Text »    PDF »
The Cellular Basis of GABAB-Mediated Interhemispheric Inhibition.
L. M. Palmer, J. M. Schulz, S. C. Murphy, D. Ledergerber, M. Murayama, and M. E. Larkum (2012)
Science 335, 989-993
   Abstract »    Full Text »    PDF »
A Novel Functionally Distinct Subtype of Striatal Neuropeptide Y Interneuron.
O. Ibanez-Sandoval, F. Tecuapetla, B. Unal, F. Shah, T. Koos, and J. M. Tepper (2011)
J. Neurosci. 31, 16757-16769
   Abstract »    Full Text »    PDF »
Expression of Gap Junction Protein Connexin36 in Multiple Subtypes of GABAergic Neurons in Adult Rat Somatosensory Cortex.
Y. Ma, H. Hioki, M. Konno, S. Pan, H. Nakamura, K. C. Nakamura, T. Furuta, J.-l. Li, and T. Kaneko (2011)
Cereb Cortex 21, 2639-2649
   Abstract »    Full Text »    PDF »
Ivy and Neurogliaform Interneurons Are a Major Target of {micro}-Opioid Receptor Modulation.
E. Krook-Magnuson, L. Luu, S.-H. Lee, C. Varga, and I. Soltesz (2011)
J. Neurosci. 31, 14861-14870
   Abstract »    Full Text »    PDF »
Specificity of Synaptic Connectivity between Layer 1 Inhibitory Interneurons and Layer 2/3 Pyramidal Neurons in the Rat Neocortex.
C. Wozny and S. R. Williams (2011)
Cereb Cortex 21, 1818-1826
   Abstract »    Full Text »    PDF »
Neurogliaform cells and other interneurons of stratum lacunosum-moleculare gate entorhinal-hippocampal dialogue.
M. Capogna (2011)
J. Physiol. 589, 1875-1883
   Abstract »    Full Text »    PDF »
Loss of COUP-TFI Alters the Balance between Caudal Ganglionic Eminence- and Medial Ganglionic Eminence-Derived Cortical Interneurons and Results in Resistance to Epilepsy.
S. Lodato, G. S. Tomassy, E. De Leonibus, Y. G. Uzcategui, G. Andolfi, M. Armentano, A. Touzot, J. M. Gaztelu, P. Arlotta, L. Menendez de la Prida, et al. (2011)
J. Neurosci. 31, 4650-4662
   Abstract »    Full Text »    PDF »
The Largest Group of Superficial Neocortical GABAergic Interneurons Expresses Ionotropic Serotonin Receptors.
S. Lee, J. Hjerling-Leffler, E. Zagha, G. Fishell, and B. Rudy (2010)
J. Neurosci. 30, 16796-16808
   Abstract »    Full Text »    PDF »
Distinctive Classes of GABAergic Interneurons Provide Layer-Specific Phasic Inhibition in the Anterior Piriform Cortex.
N. Suzuki and J. M. Bekkers (2010)
Cereb Cortex 20, 2971-2984
   Abstract »    Full Text »    PDF »
Laminar analysis of slow wave activity in humans.
R. Csercsa, B. Dombovari, D. Fabo, L. Wittner, L. Eross, L. Entz, A. Solyom, G. Rasonyi, A. Szucs, A. Kelemen, et al. (2010)
Brain 133, 2814-2829
   Abstract »    Full Text »    PDF »
Slow GABA Transient and Receptor Desensitization Shape Synaptic Responses Evoked by Hippocampal Neurogliaform Cells.
T. Karayannis, D. Elfant, I. Huerta-Ocampo, S. Teki, R. S. Scott, D. A. Rusakov, M. V. Jones, and M. Capogna (2010)
J. Neurosci. 30, 9898-9909
   Abstract »    Full Text »    PDF »
Granule Cells in the CA3 Area.
J. Szabadics, C. Varga, J. Brunner, K. Chen, and I. Soltesz (2010)
J. Neurosci. 30, 8296-8307
   Abstract »    Full Text »    PDF »
Unitary inhibitory field potentials in the CA3 region of rat hippocampus.
M. l. Bazelot, C. l. Dinocourt, I. Cohen, and R. Miles (2010)
J. Physiol. 588, 2077-2090
   Abstract »    Full Text »    PDF »
Local Control of Postinhibitory Rebound Spiking in CA1 Pyramidal Neuron Dendrites.
G. A. Ascoli, S. Gasparini, V. Medinilla, and M. Migliore (2010)
J. Neurosci. 30, 6434-6442
   Abstract »    Full Text »    PDF »
Common Origins of Hippocampal Ivy and Nitric Oxide Synthase Expressing Neurogliaform Cells.
L. Tricoire, K. A. Pelkey, M. I. Daw, V. H. Sousa, G. Miyoshi, B. Jeffries, B. Cauli, G. Fishell, and C. J. McBain (2010)
J. Neurosci. 30, 2165-2176
   Abstract »    Full Text »    PDF »
Genetic Fate Mapping Reveals That the Caudal Ganglionic Eminence Produces a Large and Diverse Population of Superficial Cortical Interneurons.
G. Miyoshi, J. Hjerling-Leffler, T. Karayannis, V. H. Sousa, S. J. B. Butt, J. Battiste, J. E. Johnson, R. P. Machold, and G. Fishell (2010)
J. Neurosci. 30, 1582-1594
   Abstract »    Full Text »    PDF »
Input-Specific GABAergic Signaling to Newborn Neurons in Adult Dentate Gyrus.
S. J. Markwardt, J. I. Wadiche, and L. S. Overstreet-Wadiche (2009)
J. Neurosci. 29, 15063-15072
   Abstract »    Full Text »    PDF »
Interneuron Diversity in Layers 2-3 of Monkey Prefrontal Cortex.
A. V. Zaitsev, N. V. Povysheva, G. Gonzalez-Burgos, D. Rotaru, K. N. Fish, L. S. Krimer, and D. A. Lewis (2009)
Cereb Cortex 19, 1597-1615
   Abstract »    Full Text »    PDF »
Distinct Roles of GABAA and GABAB Receptors in Balancing and Terminating Persistent Cortical Activity.
E. O. Mann, M. M. Kohl, and O. Paulsen (2009)
J. Neurosci. 29, 7513-7518
   Abstract »    Full Text »    PDF »
Functional Specificity of Mossy Fiber Innervation of GABAergic Cells in the Hippocampus.
J. Szabadics and I. Soltesz (2009)
J. Neurosci. 29, 4239-4251
   Abstract »    Full Text »    PDF »
L2/3 Interneuron Groups Defined by Multiparameter Analysis of Axonal Projection, Dendritic Geometry, and Electrical Excitability.
M. Helmstaedter, B. Sakmann, and D. Feldmeyer (2009)
Cereb Cortex 19, 951-962
   Abstract »    Full Text »    PDF »
Neuronal Correlates of Local, Lateral, and Translaminar Inhibition with Reference to Cortical Columns.
M. Helmstaedter, B. Sakmann, and D. Feldmeyer (2009)
Cereb Cortex 19, 926-937
   Abstract »    Full Text »    PDF »
Classification of NPY-Expressing Neocortical Interneurons.
A. Karagiannis, T. Gallopin, C. David, D. Battaglia, H. Geoffroy, J. Rossier, E. M. C. Hillman, J. F. Staiger, and B. Cauli (2009)
J. Neurosci. 29, 3642-3659
   Abstract »    Full Text »    PDF »
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G. Gonzalez-Burgos, D. C. Rotaru, A. V. Zaitsev, N. V. Povysheva, and D. A. Lewis (2009)
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   Abstract »    Full Text »    PDF »
Laminar Specificity of Functional Input to Distinct Types of Inhibitory Cortical Neurons.
X. Xu and E. M. Callaway (2009)
J. Neurosci. 29, 70-85
   Abstract »    Full Text »    PDF »
Efficient Recruitment of Layer 2/3 Interneurons by Layer 4 Input in Single Columns of Rat Somatosensory Cortex.
M. Helmstaedter, J. F. Staiger, B. Sakmann, and D. Feldmeyer (2008)
J. Neurosci. 28, 8273-8284
   Abstract »    Full Text »    PDF »
Neuronal Diversity and Temporal Dynamics: The Unity of Hippocampal Circuit Operations.
T. Klausberger and P. Somogyi (2008)
Science 321, 53-57
   Abstract »    Full Text »    PDF »
GABAB Receptor Modulation of Feedforward Inhibition through Hippocampal Neurogliaform Cells.
C. J. Price, R. Scott, D. A. Rusakov, and M. Capogna (2008)
J. Neurosci. 28, 6974-6982
   Abstract »    Full Text »    PDF »
Inhibitory Network Interactions Shape the Auditory Processing of Natural Communication Signals in the Songbird Auditory Forebrain.
R. Pinaud, T. A. Terleph, L. A. Tremere, M. L. Phan, A. A. Dagostin, R. M. Leao, C. V. Mello, and D. S. Vicario (2008)
J Neurophysiol 100, 441-455
   Abstract »    Full Text »    PDF »
Quantitative Chemical Composition of Cortical GABAergic Neurons Revealed in Transgenic Venus-Expressing Rats.
M. Uematsu, Y. Hirai, F. Karube, S. Ebihara, M. Kato, K. Abe, K. Obata, S. Yoshida, M. Hirabayashi, Y. Yanagawa, et al. (2008)
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   Abstract »    Full Text »    PDF »
The transience of interneuron circuit diversity just "sped" up.
E. Krook-Magnuson and M. M. Huntsman (2007)
PNAS 104, 16723-16724
   Full Text »    PDF »
Different transmitter transients underlie presynaptic cell type specificity of GABAA,slow and GABAA,fast.
J. Szabadics, G. Tamas, and I. Soltesz (2007)
PNAS 104, 14831-14836
   Abstract »    Full Text »    PDF »
Dopamine Increases Inhibition in the Monkey Dorsolateral Prefrontal Cortex through Cell Type-Specific Modulation of Interneurons.
S. Kroner, L. S. Krimer, D. A. Lewis, and G. Barrionuevo (2007)
Cereb Cortex 17, 1020-1032
   Abstract »    Full Text »    PDF »
Electrophysiological Differences Between Neurogliaform Cells From Monkey and Rat Prefrontal Cortex.
N. V. Povysheva, A. V. Zaitsev, S. Kroner, O. A. Krimer, D. C. Rotaru, G. Gonzalez-Burgos, D. A. Lewis, and L. S. Krimer (2007)
J Neurophysiol 97, 1030-1039
   Abstract »    Full Text »    PDF »
Neocortical Inhibitory Terminals Innervate Dendritic Spines Targeted by Thalamocortical Afferents.
Y. Kubota, S. Hatada, S. Kondo, F. Karube, and Y. Kawaguchi (2007)
J. Neurosci. 27, 1139-1150
   Abstract »    Full Text »    PDF »
Correlation Between Axonal Morphologies and Synaptic Input Kinetics of Interneurons from Mouse Visual Cortex.
D. Dumitriu, R. Cossart, J. Huang, and R. Yuste (2007)
Cereb Cortex 17, 81-91
   Abstract »    Full Text »    PDF »
Time-Dependent, Layer-Specific Modulation of Sensory Responses Mediated by Neocortical Layer 1.
D. Shlosberg, Y. Amitai, and R. Azouz (2006)
J Neurophysiol 96, 3170-3182
   Abstract »    Full Text »    PDF »
The cellular basis for parallel neural transmission of a high-frequency stimulus and its low-frequency envelope.
J. W. Middleton, A. Longtin, J. Benda, and L. Maler (2006)
PNAS 103, 14596-14601
   Abstract »    Full Text »    PDF »
Realistic Modeling of Entorhinal Cortex Field Potentials and Interpretation of Epileptic Activity in the Guinea Pig Isolated Brain Preparation.
E. Labyt, L. Uva, M. de Curtis, and F. Wendling (2006)
J Neurophysiol 96, 363-377
   Abstract »    Full Text »    PDF »
Cluster Analysis-Based Physiological Classification and Morphological Properties of Inhibitory Neurons in Layers 2-3 of Monkey Dorsolateral Prefrontal Cortex.
L. S. Krimer, A. V. Zaitsev, G. Czanner, S. Kroner, G. Gonzalez-Burgos, N. V. Povysheva, S. Iyengar, G. Barrionuevo, and D. A. Lewis (2005)
J Neurophysiol 94, 3009-3022
   Abstract »    Full Text »    PDF »
Electrical Coupling between Interneurons with Different Excitable Properties in the Stratum Lacunosum-Moleculare of the Juvenile CA1 Rat Hippocampus.
V. Zsiros and G. Maccaferri (2005)
J. Neurosci. 25, 8686-8695
   Abstract »    Full Text »    PDF »
Reducing Contralateral SI Activity Reveals Hindlimb Receptive Fields in the SI Forelimb-Stump Representation of Neonatally Amputated Rats.
C. P. Pluto, N. L. Chiaia, R. W. Rhoades, and R. D. Lane (2005)
J Neurophysiol 94, 1727-1732
   Abstract »    Full Text »    PDF »
Neurogliaform Neurons Form a Novel Inhibitory Network in the Hippocampal CA1 Area.
C. J. Price, B. Cauli, E. R. Kovacs, A. Kulik, B. Lambolez, R. Shigemoto, and M. Capogna (2005)
J. Neurosci. 25, 6775-6786
   Abstract »    Full Text »    PDF »
Gap-Junctional Coupling between Neurogliaform Cells and Various Interneuron Types in the Neocortex.
A. Simon, S. Olah, G. Molnar, J. Szabadics, and G. Tamas (2005)
J. Neurosci. 25, 6278-6285
   Abstract »    Full Text »    PDF »
Integration of Synaptic Responses to Neighboring Whiskers in Rat Barrel Cortex In Vivo.
M. J. Higley and D. Contreras (2005)
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   Abstract »    Full Text »    PDF »
Defined types of cortical interneurone structure space and spike timing in the hippocampus.
P. Somogyi and T. Klausberger (2005)
J. Physiol. 562, 9-26
   Abstract »    Full Text »    PDF »
Excitatory and inhibitory connections show selectivity in the neocortex.
J. Watts and A. M. Thomson (2005)
J. Physiol. 562, 89-97
   Abstract »    Full Text »    PDF »
Structure of cortical microcircuit theory.
C. Foldy, J. Dyhrfjeld-Johnsen, and I. Soltesz (2005)
J. Physiol. 562, 47-54
   Abstract »    Full Text »    PDF »
Experience and Activity-Dependent Maturation of Perisomatic GABAergic Innervation in Primary Visual Cortex during a Postnatal Critical Period.
B. Chattopadhyaya, G. Di Cristo, H. Higashiyama, G. W. Knott, S. J. Kuhlman, E. Welker, and Z. J. Huang (2004)
J. Neurosci. 24, 9598-9611
   Abstract »    Full Text »    PDF »
Chandelier Cells Control Excessive Cortical Excitation: Characteristics of Whisker-Evoked Synaptic Responses of Layer 2/3 Nonpyramidal and Pyramidal Neurons.
Y. Zhu, R. L. Stornetta, and J. J. Zhu (2004)
J. Neurosci. 24, 5101-5108
   Abstract »    Full Text »    PDF »
Axon Branching and Synaptic Bouton Phenotypes in GABAergic Nonpyramidal Cell Subtypes.
F. Karube, Y. Kubota, and Y. Kawaguchi (2004)
J. Neurosci. 24, 2853-2865
   Abstract »    Full Text »    PDF »
Voltage- and Site-Dependent Control of the Somatic Impact of Dendritic IPSPs.
S. R. Williams and G. J. Stuart (2003)
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   Abstract »    Full Text »    PDF »

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