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Hirac Gurden "Odor-induced neuro-astrocytic cross talk in olfactory glomeruli : control of energy metabolism and hemodynamics."

Abstract :


Energetic input is essential for information-processing in brain networks. In active areas, specific metabolic and blood flow supplies are provided by neuroenergetic coupling involving coordinated activity between neurons, astrocytes and blood vessels. Therefore, this energetic signature is widely used in brain mapping techniques such as functional Nuclear Magnetic Resonance Imaging, Positon Emission Tomography or intrinsic optical signals (IOS) imaging. However, the cellular and molecular mechanisms linking activities at the synaptic triad to neuro-imaging signals are unclear.
Astrocytes are the predominant glial cells of the central nervous system and have a primary role in the neuroenergetic coupling. They express very high levels of glutamate transporters (GLAST and GLT1) as well as connexins (30 and 43), the constitutive elements of gap junctions. In this context, we are studying the implication of these specific molecular targets in a well-defined network, the olfactory glomerulus which is the functional module of the olfactory bulb. Our work aims to determine the impact of astrocytes on the functional features of these glomeruli by complementary techniques including odor-evoked optical imaging signals.
The olfactory glomeruli receive projections from olfactory receptor neurons of the nasal epithelium and perform the first step of olfactory coding in the brain. Each odorant evokes activity in a specific pattern of glomeruli that can be mapped using IOS imaging in anesthetized rodents. These signals are due to photon absorption by changes in blood oxygenation and flow, and light scattering. Combining optical imaging, electrophysiology and local pharmacology, we have previously reported that glutamate release and uptake by astrocytes (but not postsynaptic activity) are triggers of odor-evoked IOS. We are now analyzing the impact of astrocytic glutamate transporters and connexins on sensory processing and metabolism in the olfactory glomeruli using knock-out mice for these molecules. Our recent data show a decrease in 2-Deoxy-Glucose (2DG) uptake in GLAST but not GLT1-KO mice (while GLT1 were reported to have a predominant role in the somatosensory cortex). Interestingly, the connexin30-KO mice also show different activity patterns in 2DG and IOS imaging experiments compared to wild type.Additional aspects of our work dealing with plasticity of olfactory representations (learning and memory, nutritional state of the animal) and mapping of activation using autofluorescent signals from intracellular compartments will also be described.  

Selected publications

Gurden H., Uchida N., Mainen Z. (2006) Sensory-Evoked Intrinsic Optical Signals in the Olfactory Bulb Are Coupled to Glutamate Release and Uptake.
Neuron. 52 (2) :335-345. Comment: Howarth C, Attwell D. "Transports of delight." Neuron 52 : 224-225.
     
Desbrée A, Rbah L, Langlois JB, Pain F, Pinot L, Lanièce P, Zimmer L, Gurden H. (2007) Simultaneous in vivo magnetic resonance imaging and radioactive measurements with the beta-MicroProbe. Eur J Nucl Med Mol Imaging 34 (11) : 1868-1872.