Role of glomerular inhibition in olfactory processing – Glom Inhib

We have combined electrophysiological recordings and optogenetic manipulations on acute olfactory bulb slices from transgenic mouse lines. Transgenic animals were used to identify specific periglomerular cell subtypes with fluorescent probes and to express light-gated channels in specific neuronal subtypes in order to manipulate their activity with light. Functional and synaptic properties of genetically identified neurons as well as the influence they have on principal neurons were examined using patch-clamp recordings coupled with light stimulation.

We have described the neurons and circuits mediating intraglomerular inhibition following olfactory nerve stimulation. These results have been published in The Journal Of Neuroscience (Najac et al., 2015)(see figure below). Two other articles are currently under preparation. The first is about the largest periglomerular cell population that has so far received little attention. Unexpectedly, we found that these neurons have properties of immature neurons. In the second, we describe the circuits that inhibit periglomerular interneurons. Our results suggest that they are, like most bulbar interneurons, inhibited by centrifugal afferences from neurons located outside the olfactory bulb, possibly in the horizontal limb of the diagonal band of Broca.

The unexpected discovery of many immature perigomerular neurons changes our vison of the glomerular network. This group of immature neurons constitutes an enormous potential for plasticity in the olfactory bulb network. We will thus carefully quantify this population, determine the age of these neurons and their fate when they mature and integrate the existing glomerular network.

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.

The unique synaptic architecture of the olfactory bulb transforms a well-organized incoming sensory input into an odor-specific neural code that is transmitted to higher cortical regions by mitral and tufted cells. To understand how sensory information is processed by olfactory bulb circuits I propose to investigate at the cellular, synaptic and circuit level the role of inhibition in shaping the activity of output neurons. Two layers of interneurons mediate inhibition in the bulb: periglomerular (PG) cells, a heterogeneous population of interneurons that surround each glomerulus and generate intraglomerular inhibition, and granule cells that mediate lateral inhibition of mitral and tufted cells. Whereas granule cells have been extensively studied, the functions and properties of PG cells have remained largely unexplored. My objective is to clarify the role of intraglomerular inhibition in odor processing. A potent inhibition balances the excitatory response of mitral and tufted cells to an olfactory nerve input. Our preliminary data indicate that intraglomerular circuits mediate this inhibition. I will explore several issues regarding this inhibitory pathway. First, how does it influence the glomerulus output? We will test in vivo and in slices the hypothesis that glomerular inhibition may desynchronize the firing of mitral and tufted cells projecting into the same glomerulus. Recent models of olfactory processing suggest that such decorrelation could optimize odor representation in the cortex. Second, I will identify which subtype of PG cells mediates this inhibition. Thus, I propose to examine the functional properties, synaptic connections, responses to odor and influence of two genetically-identified PG cell subtypes that synapse onto mitral and tufted cells. Finally, I will examine how multi-glomerular inhibitory inputs onto PG cells may impact the bulb output. To fulfill these objectives, I will perform patch-clamp paired-recording in olfactory bulb slices and targeted patch-clamp recording in anesthetized animals. My ambition with the present ANR Jeune Chercheur grant is to start an independent group that will use in vitro and in vivo experimental approaches with state of the art techniques in imaging and electrophysiology to address key questions about the olfactory bulb network physiology.