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Séminaire - Mariano Soiza-ReillySynaptic Organization of the Dorsal Raphe Revealed by Array Tomography

Abstract :

The Dorsal Raphe Nucleus (DR), the main source of brain’s serotonin, is implicated in the pathophysiology and therapeutics of several mental disorders that can be debilitating and life-long including depression, anxiety and autism. The activity of DR neurons is precisely regulated, both phasically and tonically, by excitatory glutamate and inhibitory GABAergic axons arising from extra-raphe areas as well as from local sources within the DR. Changes in serotonin neurotransmission associated with pathophysiology may be encoded by alterations within this network of regulatory afferents.
However, the complex organization of the DR circuitry remains still poorly understood.  Using a recently developed high-resolution immunofluorescence technique called array tomography we quantitatively analyzed the relative contribution of different populations of glutamate axons originated from different brain regions to the excitatory drive of the DR. Additionally, we examined the presence of GABA axons within the DR and their possible association with glutamate axons using array tomography as well as electron microscopy.

This analysis revealed that a third or more of GABA-containing axons are organized in synaptic triads with a glutamatergic axon and a common postsynaptic target. Further, electrophysiological recordings showed that GABA has the capacity to presynaptically gate glutamate release in the DR through a combination of GABA-A and GABA-B receptor-mediated effects. Thus, GABA-glutamate synaptic triads are a common feature of the network architecture of the DR with the potential to regulate excitation of the nucleus.

Understanding of the synaptic architecture of neural circuits, and how they organize in space will help to elucidate whether specific anatomical features could be altered under pathological states. 

Selected publications

Soiza-Reilly M., Commons, K.G. 2011. Glutamatergic drive of the dorsal raphe nucleus. J Chem Neuroanat 41 (4): 247-255.

 Soiza-Reilly, M., Commons, K.G. 2011. Quantitative analysis of glutamatergic Innervation of the mouse dorsal raphe nucleus using array tomography. J Comp Neurol 519 (18): 3802-3814.

 Soiza-Reilly, M., Anderson, W. B., Vaughan, C.W., Commons, K.G. 2013. Presynaptic gating of excitation in the dorsal raphe nucleus by GABA. Proc Natl Acad Sci U S A 110(39):15800-5.