GABAergic inhibition at dendrodendritic synapses tunes gamma oscillations in the olfactory bulb.
In the olfactory bulb (OB), odorants induce oscillations in the gamma 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 gamma oscillations remain unknown. Here, we assessed the role of the dendrodendritic inhibition, using mice lacking the GABA(A) receptor alpha1-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 alpha3-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 gamma 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.
Lagier
Samuel
S
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.
Panzanelli
Patrizia
P
Russo
Raúl E
RE
Nissant
Antoine
A
Bathellier
Brice
B
Sassoè-Pognetto
Marco
M
Fritschy
Jean-Marc
JM
Lledo
Pierre-Marie
PM
D000818:Animals; D003712:Dendrites / Q000378:metabolism*; D053444:Inhibitory Postsynaptic Potentials; D051379:Mice; D008959:Models, Neurological; D009830:Olfactory Bulb / Q000378:metabolism* / Q000648:ultrastructure; D010641:Phenotype; D011963:Receptors, GABA-A / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid