CIRB
Neural Circuits and Behavior
Director: Alexander Fleischmann
Our laboratory is interested in the functional properties of neural circuits underlying olfactory sensory processing. We use a combination of molecular genetic, in vivo imaging and behavioral approaches in mice to understand the logic of odor coding in higher olfactory centers in the cortex.
Odor perception involves the recognition of odorants in the periphery as well as central mechanisms in the brain that allow the discrimination of odors and appropriate behavioral responses. Odorants are recognized by odorant receptors, expressed in olfactory sensory neurons in the nose. Odors activate subsets of sensory neurons and result in sparse and spatially invariant pattern of glomerular activity in the olfactory bulb, the first processing center of olfactory information in the brain. Information encoded by glomerular activity is then transmitted to higher olfactory centers in the cortex, which are thought to link odor representations to appropriate behavioral responses.
Central to understanding olfactory processing is the elucidation of the functional properties of the underlying neural circuits. In an effort to address this fundamental problem in sensory biology, we have altered the patterns of neural activity evoked by odors, by generating transgenic mice in which 95% of all sensory neurons express the same receptor (Fleischmann et al., 2008). Two-photon in vivo imaging and behavioral analyses of these transgenic mice suggest a model of olfactory processing in which the recognition of patterns of neural activity, or contrast, is critical for odor detection. To test this model, we exploit a set of defined genetic perturbations in transgenic mice, which alter the expression of odorant receptor genes. We employ state-of-the-art in vivo imaging approaches to reveal how genetically defined patterns of glomerular activity are transformed into higher order odor representations in the cortex. Finally, we examine the consequences of such perturbations in assays for innate and learned olfactory-driven behaviors.
The laboratory uses an interdisciplinary approach, combining molecular mouse genetics, in vivo brain imaging and behavioral experiments and seeks to answer key questions in sensory biology and neural circuit function that are relevant to all sensory modalities.
Figure 1.
Mice with a 'monoclonal nose' : perturbations in the olfactory map impair odor discrimination. (A) Genetic strategy to express the M71 odorant receptor in all olfactory sensory neurons. Expression of the tetO-M71 transgene can be activated by the expression of tTA from the OMP locus. (B) Sensory neurons expressing the M71 transgene are marked by X-gal staining in a whole-mount preparation. OE: olfactory epithelium, VNO: vomeronasal organ, OB: olfactory bulb. (C and D) Staining with anti-M71 antibody of histological sections through the olfactory epithelium of control (C) and M71 transgenic mice (D).
Selected publications
- Glinka M.E., Samuels B.A., Teillon J., Mei D.F., Shykind B.M., Hen R. & Fleischmann A. (2012), Olfactory deficits cause anxiety-like behaviors in mice. J. Neurosci., in press.
- Choi G.B., Stettler D.D., Kallman B.R., Bhaskar S.T., Fleischmann A. & Axel R. (2011), Driving opposing behaviors with ensembles of piriform neurons. Cell 146:1004-1015
- Fleischmann A., Shykind B.M., Sosulski D.L., Franks K.M, Glinka M.E., Mei D.F., Yonghua S., Kirkland J., Mendelsohn M., Albers M.W. & Axel R. (2008), Mice with a "monoclonal" nose: perturbations in an olfactory map impair odor discrimination. Neuron. Dec 26; (60):1-14.
- Fleischmann A., Jochum W., Eferl R., Witowsky J. & Wagner E.F. (2003), Rhabdomyosarcoma development in mice lacking Trp53 and Fos: tumor suppression by the Fos protooncogene. Cancer Cell. Dec;4(6):477-82.
- Fleischmann A., Hvalby O., Jensen V., Strekalova T., Zacher C., Layer L.E., Kvello A., Reschke M., Spanagel R., Sprengel R., Wagner E.F. & Gass P. (2003), Impaired long-term memory and NR2A-type NMDA receptor-dependent synaptic plasticity in mice lacking c-Fos in the CNS. J Neurosci. Oct 8;23(27):9116-22.
- Fleischmann A., Hafezi F., Elliott C., Reme C.E., Ruther U. & Wagner E.F. (2000), Fra-1 replaces c-Fos-dependent functions in mice. Genes Dev. Nov 1;14(21):2695-700.
- Sibilia M., Fleischmann A., Behrens A., Stingl L., Carroll J., Watt F.M., Schlessinger J. & Wagner E.F. (2000), The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development. Cell. Jul 21;102(2):211-20.