GABAergic inhibition at dendrodendritic synapses tunes γ oscillations in the olfactory bulb

^†Laboratory of Perception and Memory, Centre National de la Recherche Scientifique, Unité de Recherche Associée 2182, Institut Pasteur, 25 Rue du Dr. Roux, F-75724 Paris Cedex 15, France;
^‡Department of Anatomy, Pharmacology, and Forensic Medicine and
^‖Istituto Nazionale di Neuroscienze, University of Turin, I-10126 Turin, Italy;
^¶Laboratory of Computational Neuroscience, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland;
^††Institute of Pharmacology and Toxicology, University of Zurich, CH-8057 Zurich, Switzerland; and
^§Neurofisiolgía Celulary Molecular, Instituto de Investigaciones Biológicas, Clemente Estable, Avenida Italia 3318, CP 11600 Montevideo, Uruguay

Communicated by D. Carleton Gajdusek, Institut de Neurobiologie Alfred Fessard, Gif-sur-Yvette, France, March 5, 2007 (received for review November 7, 2006)

Abstract

In the olfactory bulb (OB), odorants induce oscillations in the γ range (20–80 Hz) that play an important role in the processing of sensory information. Synaptic transmission between dendrites is a major contributor to this processing. Glutamate released from mitral cell dendrites excites the dendrites of granule cells, which in turn mediate GABAergic inhibition back onto mitral cells. Although this reciprocal synapse is thought to be a key element supporting oscillatory activity, the mechanisms by which dendrodendritic inhibition induces and maintains γ oscillations remain unknown. Here, we assessed the role of the dendrodendritic inhibition, using mice lacking the GABA_A receptor α1-subunit, which is specifically expressed in mitral cells but not in granule cells. The spontaneous inhibitory postsynaptic current frequency in these mutants was low and was consistent with the reduction of GABA_A receptor clusters detected by immunohistochemistry. The remaining GABA_A receptors in mitral cells contained the α3-subunit and supported slower decaying currents of unchanged amplitude. Overall, inhibitory-mediated interactions between mitral cells were smaller and slower in mutant than in WT mice, although the strength of sensory afferent inputs remained unchanged. Consequently, both experimental and theoretical approaches revealed slower γ oscillations in the OB network of mutant mice. We conclude, therefore, that fast oscillations in the OB circuit are strongly constrained by the precise location, subunit composition and kinetics of GABA_A receptors expressed in mitral cells.

Footnotes

^‡‡To whom correspondence should be addressed. E-mail: pmlledo{at}pasteur.fr
Author contributions: S.L., P.P., J.-M.F., and P.-M.L. contributed equally to this work; M.S.-P., J.-M.F., and P.-M.L. designed research; S.L., P.P., R.E.R., A.N., B.B., and J.-M.F. performed research; S.L., A.N., B.B., M.S.-P., and P.-M.L. analyzed data; and S.L., J.-M.F., and P.-M.L. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0701846104/DC1.
↵*Migliore, M., Shepherd, G.M. (2006) Soc. Neurosci. Abstr. 797:15 (abstr.).
Abbreviations:

DDI,

dendrodendritic inhibition;

EPL,

external plexiform layer;

GCL,

granule cell layer;

IPSC,

inhibitory postsynaptic current;

LFP,

local field potentials;

OB,

olfactory bulb;

sIPSC,

spontaneous inhibitory postsynaptic current;

uIPSC,

unitary inhibitory postsynaptic current.