Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 326 (5951): 449-453

Copyright © 2009 by the American Association for the Advancement of Science

Fast Synaptic Subcortical Control of Hippocampal Circuits

Viktor Varga,1,*,{dagger} Attila Losonczy,2,*,{dagger},{ddagger} Boris V. Zemelman,2,* Zsolt Borhegyi,1 Gábor Nyiri,1 Andor Domonkos,1 Balázs Hangya,1 Noémi Holderith,1 Jeffrey C. Magee,2 Tamás F. Freund1

Abstract: Cortical information processing is under state-dependent control of subcortical neuromodulatory systems. Although this modulatory effect is thought to be mediated mainly by slow nonsynaptic metabotropic receptors, other mechanisms, such as direct synaptic transmission, are possible. Yet, it is currently unknown if any such form of subcortical control exists. Here, we present direct evidence of a strong, spatiotemporally precise excitatory input from an ascending neuromodulatory center. Selective stimulation of serotonergic median raphe neurons produced a rapid activation of hippocampal interneurons. At the network level, this subcortical drive was manifested as a pattern of effective disynaptic GABAergic inhibition that spread throughout the circuit. This form of subcortical network regulation should be incorporated into current concepts of normal and pathological cortical function.

1 Institute of Experimental Medicine, Budapest 1083, Hungary.
2 Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA 20147, USA.

* These authors contributed equally to this work.

{dagger} Present address: Department of Neuroscience, Columbia University, New York, NY 10032, USA.

{dagger} To whom correspondence should be addressed. E-mail: vargav{at} (V.V.), losonczya{at} (A.L.)

Cholinergic Inputs from Basal Forebrain Add an Excitatory Bias to Odor Coding in the Olfactory Bulb.
M. Rothermel, R. M. Carey, A. Puche, M. T. Shipley, and M. Wachowiak (2014)
J. Neurosci. 34, 4654-4664
   Abstract »    Full Text »    PDF »
Temporal redistribution of inhibition over neuronal subcellular domains underlies state-dependent rhythmic change of excitability in the hippocampus.
P. Somogyi, L. Katona, T. Klausberger, B. Lasztoczi, and T. J. Viney (2014)
Phil Trans R Soc B 369, 20120518
   Abstract »    Full Text »    PDF »
The Synchronous Activity of Lateral Habenular Neurons Is Essential for Regulating Hippocampal Theta Oscillation.
H. Aizawa, S. Yanagihara, M. Kobayashi, K. Niisato, T. Takekawa, R. Harukuni, T. J. McHugh, T. Fukai, Y. Isomura, and H. Okamoto (2013)
J. Neurosci. 33, 8909-8921
   Abstract »    Full Text »    PDF »
Mechanisms Generating Dual-Component Nicotinic EPSCs in Cortical Interneurons.
C. Bennett, S. Arroyo, D. Berns, and S. Hestrin (2012)
J. Neurosci. 32, 17287-17296
   Abstract »    Full Text »    PDF »
Direct Alteration of a Specific Inhibitory Circuit of the Hippocampus by Antidepressants.
P. Mendez, A. Pazienti, G. Szabo, and A. Bacci (2012)
J. Neurosci. 32, 16616-16628
   Abstract »    Full Text »    PDF »
The vesicular glutamate transporter VGLUT3 contributes to protection against neonatal hypoxic stress.
S. Miot, N. Voituron, A. Sterlin, E. Vigneault, L. Morel, B. Matrot, N. Ramanantsoa, B. Amilhon, O. Poirel, E. Lepicard, et al. (2012)
J. Physiol. 590, 5183-5198
   Abstract »    Full Text »    PDF »
Probing the diversity of serotonin neurons.
P. Gaspar and C. Lillesaar (2012)
Phil Trans R Soc B 367, 2382-2394
   Abstract »    Full Text »    PDF »
Targeting brain serotonin synthesis: insights into neurodevelopmental disorders with long-term outcomes related to negative emotionality, aggression and antisocial behaviour.
K.-P. Lesch, N. Araragi, J. Waider, D. van den Hove, and L. Gutknecht (2012)
Phil Trans R Soc B 367, 2426-2443
   Abstract »    Full Text »    PDF »
Development of GABAergic inputs controls the contribution of maturing neurons to the adult hippocampal network.
Y. Li, J. B. Aimone, X. Xu, E. M. Callaway, and F. H. Gage (2012)
PNAS 109, 4290-4295
   Abstract »    Full Text »    PDF »
Sticking out of the crowd: the molecular identity and development of cholecystokinin-containing basket cells.
E. Keimpema, A. Straiker, K. Mackie, T. Harkany, and J. Hjerling-Leffler (2012)
J. Physiol. 590, 703-714
   Abstract »    Full Text »    PDF »
Vesicular and Plasma Membrane Transporters for Neurotransmitters.
R. D. Blakely and R. H. Edwards (2012)
Cold Spring Harb Perspect Biol 4, a005595
   Abstract »    Full Text »    PDF »
Co-transmission of dopamine and glutamate.
J. I. Broussard (2011)
J. Gen. Physiol. 139, 93-96
   Full Text »    PDF »
Terminal Field and Firing Selectivity of Cholecystokinin-Expressing Interneurons in the Hippocampal CA3 Area.
B. Lasztoczi, J. J. Tukker, P. Somogyi, and T. Klausberger (2011)
J. Neurosci. 31, 18073-18093
   Abstract »    Full Text »    PDF »
Cell-Type-Specific Modulation of Feedback Inhibition by Serotonin in the Hippocampus.
J. Winterer, A. V. Stempel, T. Dugladze, C. Foldy, N. Maziashvili, A. R. Zivkovic, J. Priller, I. Soltesz, T. Gloveli, and D. Schmitz (2011)
J. Neurosci. 31, 8464-8475
   Abstract »    Full Text »    PDF »
Modulation of hippocampal stratum lacunosum-moleculare microcircuits.
G. Maccaferri (2011)
J. Physiol. 589, 1885-1891
   Abstract »    Full Text »    PDF »
A Genetically Defined Morphologically and Functionally Unique Subset of 5-HT Neurons in the Mouse Raphe Nuclei.
V. Kiyasova, S. P. Fernandez, J. Laine, L. Stankovski, A. Muzerelle, S. Doly, and P. Gaspar (2011)
J. Neurosci. 31, 2756-2768
   Abstract »    Full Text »    PDF »
Channelrhodopsin as a tool to investigate synaptic transmission and plasticity.
P. Schoenenberger, Y.-P. Z. Scharer, and T. G. Oertner (2011)
Exp Physiol 96, 34-39
   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 »
Two-photon single-cell optogenetic control of neuronal activity by sculpted light.
B. K. Andrasfalvy, B. V. Zemelman, J. Tang, and A. Vaziri (2010)
PNAS 107, 11981-11986
   Abstract »    Full Text »    PDF »
Vesicular Monoamine and Glutamate Transporters Select Distinct Synaptic Vesicle Recycling Pathways.
B. Onoa, H. Li, J. A. Gagnon-Bartsch, L. A. B. Elias, and R. H. Edwards (2010)
J. Neurosci. 30, 7917-7927
   Abstract »    Full Text »    PDF »
Serotonin Modulates Fast-Spiking Interneuron and Synchronous Activity in the Rat Prefrontal Cortex through 5-HT1A and 5-HT2A Receptors.
M. V. Puig, A. Watakabe, M. Ushimaru, T. Yamamori, and Y. Kawaguchi (2010)
J. Neurosci. 30, 2211-2222
   Abstract »    Full Text »    PDF »
Cell Type-Specific Long-Term Plasticity at Glutamatergic Synapses onto Hippocampal Interneurons Expressing either Parvalbumin or CB1 Cannabinoid Receptor.
W. Nissen, A. Szabo, J. Somogyi, P. Somogyi, and K. P. Lamsa (2010)
J. Neurosci. 30, 1337-1347
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882