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Science 16 October 2009:
Vol. 326. no. 5951, pp. 449 - 453
DOI: 10.1126/science.1178307
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Reports

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

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}koki.hu (V.V.), losonczya{at}janelia.hhmi.org (A.L.)

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Science. ISSN 0036-8075 (print), 1095-9203 (online)