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Functional diversity of tyrosine hydroxylase-expressing short axon cells in the olfactory bulb

Research unit

UPR 3212 - Institut des Neurosciences Cellulaires et Intégratives (INCI)
5, rue Blaise Pascal, 67084 STRASBOURG

Group

Name: Physiologie des Réseaux de Neurones

Group leader: ISOPE / POULAIN - philippe.isope@inci-cnrs.unistra.fr

Group leader's phone: 0388456731

Website: Visit website

Group organization:
- Chercheurs: 6
- ITA: 1
- Doctorants: 5
- Post-Docs: 1
- Autres: 0

Publications of the team linked to the topic (3 last years):
1) Najac, M., Diez, A. S., Kumar, A., Benito, N., Charpak, S., & De Saint Jan, D. (2015). Intraglomerular Lateral Inhibition Promotes Spike Timing Variability in Principal Neurons of the Olfactory Bulb. The Journal of Neuroscience, 35(10), 4319-4331.
2) Najac, M., De Saint Jan, D., Reguero, L., Grandes, P., & Charpak, S. (2011). Monosynaptic and polysynaptic feed-forward inputs to mitral cells from olfactory sensory neurons. The Journal of Neuroscience, 31(24), 8722-8729.
3) De Saint Jan, D., Hirnet, D., Westbrook, G. L., & Charpak, S. (2009). External tufted cells drive the output of olfactory bulb glomeruli. The Journal of Neuroscience, 29(7), 2043-2052.

About PhD

PhD Director: DE SAINT JAN Didier - desaintjan@inci-cnrs.unistra.fr

Phone: 0388456744

Junior advisor: non

Co-tutely: non

Co-Director: non

About PhD topic :

Title: Functional diversity of tyrosine hydroxylase-expressing short axon cells in the olfactory bulb

Project: The diversity of inhibitory interneurons is an ubiquitous finding in the central nervous system. Understanding the mechanisms and functional implications underlying this diversity is a real challenge in modern neuroscience. This question is particularly relevant in the olfactory bulb, the first station for odor processing in the brain, where 80-90% of the neurons are inhibitory and continuously generated after birth from neural stem cells, suggesting that inhibition plays a critical role in odor processing.
The olfactory bulb receives sensory inputs from olfactory sensory neurons (OSN) that detect odorants in the nasal epithelium. OSN axons activate mitral and tufted cells, the principal neurons of the olfactory bulb, within spherical structures called glomeruli. Importantly, OSN expressing the same olfactory receptor converge within two specific glomeruli in each bulb and make synapses on the unique apical dendrite of mitral and tufted cells. Thus, mitral and tufted cells receive sensory inputs from a single glomerulus-specific set of OSNs.
Each of the ~1800 glomeruli lining at the surface of each bulb is surrounded by a diversity of juxtaglomerular interneurons that modulate the integration of sensory information by mitral and tufted cells. Short axon (SA) cells are mixed GABAergic/dopaminergic juxtaglomerular neurons that selectively express tyrosine hydroxylase (TH). Contrary to what their name suggests, they rely on long axonal ramifications to interact with other cell types across many glomeruli. Recent papers have shown that they inhibit external tufted cells, a key intermediate neuronal type that gates the synaptic activation of mitral and tufted cells. The function of this interglomerular inhibitory circuit is at present unclear but in theory it may entrain and synchronize the activity of different glomeruli or, in contrast, suppress the activity of mitral and tufted cells in surrounding glomeruli thereby mediating contrast enhancement.
At least two populations of TH-expressing SA cells with different morphologies and temporal origins have been described. TH-expressing SA cells with large somata make long interglomerular projections and are mainly generated prenatally but not in juveniles or adults. In contrast, TH(+) cells with small somata are generated postnatally in juvenile and adult animals and extend their processes in only few glomeruli. It is still unclear whether each of these morphotypes have different embryonic origins, specific electrophysiological properties, distinct synaptic connections and, ultimately, different functions. The candidate will combine patch-clamp recording, stem cells electroporation and optogenetic stimulation to address these questions. SA cells will be identified and manipulated using viral expression of cre-dependent markers and light-gated channels in transgenic mice expressing the Cre recombinase in TH-expressing neurons.

Wished skills: Experience in electrophysiology solid background in synaptic physiology

Expertises which will be acquired during the training: Slice physiology
patch-clamp recording
Stem cell electroporation
immunohistchemistry