Cycle 4 project 8

Role of olfactory bulb excitatory interneurons in odor processing and adult bulbar neurogenesis


Dorina FrasheriPhD student: Dorina Frasheri, Albania
Home Institute: Neuroscience Center Zürich; Principle Investigator: Olivier Raineteau
Host Institute: Bordeaux Neurocampus; Principle Investigator: Muriel Koehl
2nd Host Institute: Amsterdam Neuroscience; Principle Investigator: Wilma van de Berg

Executive Summary

The rodent olfactory bulb (OB) is a model system for studying how neuronal circuits develop and maintain. Olfactory receptor neurons in the main olfactory epithelium project their axons to glomerular structures in the OB. There, they synapse onto the dendrites of mitral and tufted cells that relay odour information to higher brain centres. In the OB, odour information is processed by local interneurons, which are either inhibitory (i.e. periglomerular interneurons and granule cells), or excitatory (i.e. external tufted cells and short axon cells).

OB inhibitory interneurons continue to be generated throughout adulthood by neural stem cells (NSCs) located in the walls of the lateral ventricles. The discovery of this ongoing neurogenesis has raised great hopes for the development of new regenerative approaches. Because of this, their function and the molecular determinant of their continuous genesis have been studied in great details (e.g. Abrous et al., Physiol Rev 2005).

Much less is known about OB excitatory interneurons. We have recently shown that external tufted cells (ET-cells) and short axon cells (SA-cells) are produced sequentially during late embryonic development (Winpenny et al., 2011). ET-cells show dendrites ramifying within a single glomerulus, and receive monosynaptic input from the olfactory nerve that is converted into an all-or-none spike burst. These properties suggest a role in amplifying suprathreshold sensory input at the first stage of synaptic transfer in the olfactory system. SA-cells in the opposite extend dendrites and axons across multiple glomeruli and are therefore likely to be involved in interglomerular functions, such as center-surround inhibition of neighbouring glomeruli (Aungst et al., 2003). These properties suggest their involvement in scent discrimination. Thus, although their morphology and synaptic connectivity suggest a key role for excitatory interneurons in olfaction, their exact function has not been tested.

While neurogenesis persists in the adult OB, recent reports have challenged the classical view of the presence of truly multipotent NSCs capable of producing a variety of neuronal subtypes in the adult forebrain. Ablation of ET- and SA-cells offers a unique opportunity to assess the plastic potential of adult-NSCs (aNSCs) by testing if they are able to change their fate from gabaergic to glutamatergic. This question is of particularly importance to assess the capacity of aNSCs to participate to brain repair.

In this project we propose to:

  • AIM 1: assess the function of both populations of excitatory interneurons in olfaction
  • AIM 2: assess if aNSCs have the plastic potential to generate excitatory neurons

This project is based on the use of a new transgenic mouse that we have recently generated and characterized (Winpenny et al., 2011). Using this mouse, we will perform genetic single or combined ablation of these 2 neuronal populations in order to address the 2 aims of this proposal. To this end, we will take advantage of the complementary expertise of the 3 participating laboratories (Stereology: W.J.D. van de Berg; behavioral analysis/adult neurogenesis: Muriel Koehl; transgenesis/fate mapping: Olivier Raineteau).




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