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Olfactory granule cell-specific silencing slows down odor discrimination time in mice

Bhavana Shrivastava1, Ruud Toonen2, Matthijs Verhage2 and Thomas Kuner1
  • 1 University of Heidelberg, Anatomy and Cell Biology II, Germany
  • 2 Vrije Universiteit, Center for Neurogenomics and Cognitive Research, Netherlands

Introduction: The granule cells (GCs) of the olfactory bulb (OB) are axonless inhibitory interneurons, which form reciprocal-dendrodendritic synapses with the first order relay neurons (Mitral/Tufted cells, MTC) of the olfactory pathway. It is upon these excitatory relay neurons, that the GCs mediate inhibition at various levels (recurrent/global-lateral/local-lateral inhibition). Our study aims to understand the contribution of GC-mediated inhibition in the OB towards odor discrimination behavior.

Material and Methods: Previously it has been shown that mice require less time to discriminate
dissimilar olfactory stimuli (amyl acetate versus ethyl butyrate) compared to discriminating similar stimuli (binary mixtures of these odorants). To assess how the extent of inhibition between GCs and MTC contributes to odor discrimination time, we silenced the GC output and examined odor
discrimination behaviour of mice. The two-fold approach adopted to investigate the effects of
completely silencing the GC mediated inhibition on the principal olfactory relay neurons, was as
follows:

(1) Targeted ablation of the essential presynaptic protein Munc18-1 was carried out by stereotaxic
delivery of r-AAV1/2 (to express Cre recombinase) in the GC layer of three week old mice carrying
floxed Munc18-1 alleles. This generated a highly specific Munc18-1 knockout in the infected GCs of the OB.

(2) Botulinum neurotoxin light chain-A was specifically expressed in the granule cell layer using
r-AAV1/2 to selectively cleave the Synaptosomal associated protein 25 (SNAP-25), which in
turn, is an essential component of the SNARE complex that enables synaptic vesicle fusion and
neurotransmitter release.

In both cases, olfactory behavioral testing (using a go, no-go operant conditioning paradigm)
revealed the pattern that mice with silenced GC output required consistently longer times to
discriminate even highly dissimilar odor stimuli with respect to their littermate controls. Besides, the discrimination time for highly similar binary mixtures of odorants remained more than for dissimilar odor pairs, as has been observed before. No significant difference was apparent in binary mixture discrimination time between the control and GC-silenced groups.

Conclusions: Thus, these results suggest a pivotal role of GC-mediated inhibition in the OB, even for the discrimination of simple odor stimuli, which was previously unknown.

Acknowledgements

We thank Claudia Kocksch and Michaela Kaiser for expert technical help and virus production. This work was funded by DFG grant Ku-1983/2 (FOR 643).

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Keywords: Behavior, Granule-cell mediated inhibition, Neuronal silencing, Odor Discrimination Time, olfactory

Conference: Human Chemosensation 2010, Dresden, Germany, 2 Dec - 4 Dec, 2010.

Presentation Type: Presentation

Topic: Human Chemosensation 2010

Citation: Shrivastava B, Toonen R, Verhage M and Kuner T (2011). Olfactory granule cell-specific silencing slows down odor discrimination time in mice. Front. Neurosci. Conference Abstract: Human Chemosensation 2010. doi: 10.3389/conf.fnins.2011.85.00012

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Received: 10 Feb 2011; Published Online: 03 May 2011.