Circuit formation and function
in the olfactory bulb

Field of Interest

Figure 1. Example of an olfactory sensory neuron stained for OMP.

Figure 1. Example of an olfactory sensory neuron stained for OMP.
[click image to enlarge]

The olfactory system (OS) is an attractive model for the study of neuronal wiring and information processing in the mammalian brain, due to the relative simplicity of its topographic and functional organization which facilitates thorough investigations.

Each olfactory sensory neuron (OSN, Fig. 1) expresses only one odorant receptor out of a repertoire of about 1000. Odorant receptors are coupled to a complex signal transduction machinery involving cyclic nucleotides, Ca²⁺ and electrical signals that are essential not only to transduce the odorant activated signal to the olfactory bulb, but also in determining the formation of specific anatomical connections. OSN expressing the same odorant receptor, in fact, converge with exquisite precision to form glomeruli in specific locations on the medial and lateral side of each bulb.

Figure 2. Schematic representation of the circuitry in the olfactory bulb: olfactory sensory neurons (OSN) expressing the same odorant receptor (same color) converge on the same glomerulus. Each glomerulus is formed by the synaptic connections of the axon of the OSN and the dendrite of the postsynaptic cells: mitral cells (MC), tufted cells (TC) and periglomerular cells (PG). GC=granule cells.

Figure 2. Schematic representation of the circuitry in the olfactory bulb: olfactory sensory neurons (OSN) expressing the same odorant receptor (same color) converge on the same glomerulus. Each glomerulus is formed by the synaptic connections of the axon of the OSN and the dendrite of the postsynaptic cells: mitral cells (MC), tufted cells (TC) and periglomerular cells (PG). GC=granule cells.
[click image to enlarge]

A glomerulus defines an "odor column" consisting of the mitral, tufted and periglomerular cells receiving input from a specific group of OSN, along with the granule cells connected to those cells (Fig. 2,3). A unique feature of this initial sensory projection is that each bulb presents two mirror symmetric maps of homologous odor columns. In our previous study we found that the two maps are reciprocally connected through an inhibitory link related to external tufted cells. The precise nature of these intrabulbar connections has several implications for the development of the bulbar circuitry and for its function.

Studying the functions and subcellular distribution of the second messengers as well as the connectivity in the olfactory system, while interesting on its own right, may also contribute to understand the general mechanisms underlying intracellular signaling and specificity of connectivity in the central nervous system in physiological and pathological situation. Indeed the olfactory system has been seen to be involved in severe psychiatric and neurological diseases, such as schizophrenia, Parkinson and Alzheimer diseases.

Second messengers in the olfactory system: modulators of functions.

Figure 3. Example of a focal tracer injection centered in a GFP labeled glomerulus. The injection labels ETC (arrowhead) innervating the glomerulus. GL, glomerular layer, EPL, external plexiform layer, MC, mitral cell layer.

Figure 3. Example of a focal tracer injection centered in a GFP labeled glomerulus. The injection labels ETC (arrowhead) innervating the glomerulus. GL, glomerular layer, EPL, external plexiform layer, MC, mitral cell layer.
[click image to enlarge]

Calcium (Ca²⁺) and cyclic adenosine monophosphate (cAMP) are ubiquitous second messengers in neurons and glial cells in the central nervous system. These second messengers are known to modulate a wide variety of biological functions. In the olfactory system (OS) Ca²⁺ and cAMP play a critical role in signal transduction, axon guidance, odor preference, memory formation, etc. How the same molecules can mediate so many different functions remain to be clarified. It has been suggested that the spatio-temporal dynamics of changes in concentration of the second messengers play a key role to achieve the specificity of cellular response.

To study the spatio-temporal dynamics of the second messengers in the olfactory system we take advantage of genetically encoded sensors for cAMP and Ca²⁺ targeted to different cellular compartments, as well as Ca²⁺ indicators (such as fura 2, Oregon green, etc).

We use in vitro and in vivo approaches, from the classical imaging apparatuses to study neuronal cultures, to the two photon microscope that allows to investigate the generation, subcellular localization and temporal dynamics of fluorescent signals not only in cell cultures or in acute tissue slices, but also in vivo with utmost spatial and temporal accuracy. The olfactory system (OS) appears a particularly attractive model for this study for a number of reasons: i) the olfactory bulb (OB) neurons and glial cells are superficially located and have been imaged in vivo even without removing the skull bone; ii) neuronal wiring and information processing in the OS is relatively simple; iii) the OB neurons are intimately connected to glial cells and thus represent an ideal in situ model to investigate the reciprocal communication between these cell types, iv) the sensory neurons, although difficult to image in the live animal (for anatomical reasons), can be easily accessed in in situ preparations and have a series of unique and highly interesting features in terms of second messenger handling. Furthermore the latter neurons can be easily infected with viral vectors by simple inhalation of the viruses and thus with minimal animal manipulation; v) the olfactory system is highly conserved among species, from Drosophila to higher mammals. This renders the olfactory system an excellent model system to study physiological and pathological conditions of the central nervous system.

Synoptic CV

VIMM Publications

• Maritan M, Monaco G, Zamparo I, Zaccolo M, Pozzan T, Lodovichi C (2009) Odorant receptors at the growth cone are coupled to localized cAMP and Ca2+ increases. Proc. Natl. Acad. Sci. U.S.A. 106:3537-42.

Additional Publications

• Cao L, Dhilla A, Mukai J, Blazeski R, Lodovichi C, Mason CA, Gogos JA (2007) Genetic modulation of BDNF signaling affects the outcome of axonal competition in vivo. Curr. Biol. 17:911-21.
• Lodovichi C, Belluscio L, Katz LC (2003) Functional topography of connections linking mirror-symmetric maps in the mouse olfactory bulb. Neuron 38:265-76.
• Belluscio L, Lodovichi C, Feinstein P, Mombaerts P, Katz LC (2002) Odorant receptors instruct functional circuitry in the mouse olfactory bulb. Nature 419:296-300.
• [Pubmed ID: 10704490 * PubMed in process or DB hiatus]
• Caleo M, Lodovichi C, Maffei L (1999) Effects of nerve growth factor on visual cortical plasticity require afferent electrical activity. Eur. J. Neurosci. 11:2979-84.

Selected Seminars

Contact

Claudia Lodovichi Venetian Institute of Molecular Medicine Via Orus 2 35129 Padua — Italy

Tel.:  (+39) 049 7923 222 Tel. lab.:  (+39) 049 7923 225 Fax:  (+39) 049 7923 266

Last updated: 28/03/2010, CL ·