Synchronous Infra-Slow Oscillations Organize Ensembles of Accessory Olfactory Bulb Projection Neurons into Distinct Microcircuits

The accessory olfactory system controls social and sexual behavior. In the mouse accessory olfactory bulb, the first central stage of information processing along the accessory olfactory pathway, projection neurons (mitral cells) display infra-slow oscillatory discharge with remarkable periodicity. The physiological mechanisms that underlie this default output state, however, remain controversial. Moreover, whether such rhythmic infra-slow activity patterns exist in awake behaving mice and whether such activity reflects the functional organization of the accessory olfactory bulb circuitry remain unclear. Here, we hypothesize that mitral cell ensembles form synchronized microcircuits that subdivide the accessory olfactory bulb into segregated functional clusters. We use a miniature microscope to image the Ca2+ dynamics within the apical dendritic compartments of large mitral cell ensembles in vivo. We show that infra-slow periodic patterns of concerted neural activity, indeed, reflect the idle state of accessory olfactory bulb output in awake male and female mice. Ca2+ activity profiles are distinct and glomerulus-specific. Confocal time-lapse imaging in acute slices reveals that groups of mitral cells assemble into microcircuits that exhibit correlated Ca2+ signals. Moreover, electrophysiological profiling of synaptic connectivity indicates functional coupling between mitral cells. Our results suggest that both intrinsically rhythmogenic neurons and neurons entrained by fast synaptic drive are key elements in organizing the accessory olfactory bulb into functional microcircuits, each characterized by a distinct default pattern of infra-slow rhythmicity

Activity-Induced Remodeling of Olfactory Bulb Microcircuits Revealed by Monosynaptic Tracing

The continued addition of new neurons to mature olfactory circuits represents a remarkable mode of cellular and structural brain plasticity. However, the anatomical configuration of newly established circuits, the types and numbers of neurons that form new synaptic connections, and the effect of sensory experience on synaptic connectivity in the olfactory bulb remain poorly understood. Using in vivo electroporation and monosynaptic tracing, we show that postnatal-born granule cells form synaptic connections with centrifugal inputs and mitral/tufted cells in the mouse olfactory bulb. In addition, newly born granule cells receive extensive input from local inhibitory short axon cells, a poorly understood cell population. The connectivity of short axon cells shows clustered organization, and their synaptic input onto newborn granule cells dramatically and selectively expands with odor stimulation. Our findings suggest that sensory experience promotes the synaptic integration of new neurons into cell type-specific olfactory circuits

Dendrodendritic synapses in the mouse olfactory bulb external plexiform layer

Odor information relayed by olfactory bulb projection neurons, mitral and tufted cells (M/T), is modulated by pairs of reciprocal dendrodendritic synaptic circuits in the external plexiform layer (EPL). Interneurons, which are accounted for largely by granule cells, receive depolarizing input from M/T dendrites and in turn inhibit current spread in M/T dendrites via hyperpolarizing reciprocal dendrodendritic synapses. Because the location of dendrodendritic synapses may significantly affect the cascade of odor information, we assessed synaptic properties and density within sublaminae of the EPL and along the length of M/T secondary dendrites. In electron micrographs the M/T to granule cell synapse appeared to predominate and was equivalent in both the outer and inner EPL. However, the dendrodendritic synapses from granule cell spines onto M/T dendrites were more prevalent in the outer EPL. In contrast, individual gephyrin-immunoreactive (IR) puncta, a postsynaptic scaffolding protein at inhibitory synapses used here as a proxy for the granule to M/T dendritic synapse was equally distributed throughout the EPL. Of significance to the organization of intrabulbar circuits, gephyrin-IR synapses are not uniformly distributed along M/T secondary dendrites. Synaptic density, expressed as a function of surface area, increases distal to the cell body. Furthermore, the distributions of gephyrin-IR puncta are heterogeneous and appear as clusters along the length of the M/T dendrites. Consistent with computational models, our data suggest that temporal coding in M/T cells is achieved by precisely located inhibitory input and that distance from the soma is compensated for by an increase in synaptic density.Fil: Bartel, Dianna L.. University Of Yale. School Of Medicine; Estados UnidosFil: Rela, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Hsieh, Lawrence. University Of Yale. School Of Medicine; Estados UnidosFil: Greer, Charles A. . University Of Yale. School Of Medicine; Estados Unido

Glomerular and mitral-granule cell microcircuits coordinate temporal and spatial information processing in the olfactory bulb

The olfactory bulb processes inputs from olfactory receptor neurons (ORNs) through two levels: the glomerular layer at the site of input, and the granule cell level at the site of output to the olfactory cortex. The sequence of action of these two levels has not yet been examined. We analyze this issue using a novel computational framework that is scaled up, in three-dimensions (3D), with realistic representations of the interactions between layers, activated by simulated natural odors, and constrained by experimental and theoretical analyses. We suggest that the postulated functions of glomerular circuits have as their primary role transforming a complex and disorganized input into a contrast-enhanced and normalized representation, but cannot provide for synchronization of the distributed glomerular outputs. By contrast, at the granule cell layer, the dendrodendritic interactions mediate temporal decorrelation, which we show is dependent on the preceding contrast enhancement by the glomerular layer. The results provide the first insights into the successive operations in the olfactory bulb, and demonstrate the significance of the modular organization around glomeruli. This layered organization is especially important for natural odor inputs, because they activate many overlapping glomeruli

A unique olfactory bulb microcircuit driven by neurons expressing the precursor to glucagon-like peptide 1

The presence of large numbers of local interneurons in the olfactory bulb has demonstrated an extensive local signaling process, yet the identification and purpose of olfactory microcircuits is poorly explored. Because the discrimination of odors in a complex environment is highly dependent on the tuning of information by local interneurons, we studied for the first time the role of preproglucagon (PPG) neurons in the granule cell layer of the olfactory bulb. Combining electrophysiological recordings and confocal microscopy, we discovered that the PPG neurons are a population of cells expressing the precursor of glucagon-like peptide 1 and are glutamatergic; able to modulate the firing pattern of the mitral cells (M/TCs). Optogenetic activation of PPG neurons resulted in a mixed excitation and inhibition that created a multiphasic response shaping the M/TCs firing pattern. This suggests that PPG neurons could drive neuromodulation of the olfactory output and change the synaptic map regulating olfactory coding

A unique olfactory bulb microcircuit driven by neurons expressing the precursor to glucagon-like peptide 1

Abstract: The presence of large numbers of local interneurons in the olfactory bulb has demonstrated an extensive local signaling process, yet the identification and purpose of olfactory microcircuits is poorly explored. Because the discrimination of odors in a complex environment is highly dependent on the tuning of information by local interneurons, we studied for the first time the role of preproglucagon (PPG) neurons in the granule cell layer of the olfactory bulb. Combining electrophysiological recordings and confocal microscopy, we discovered that the PPG neurons are a population of cells expressing the precursor of glucagon-like peptide 1 and are glutamatergic; able to modulate the firing pattern of the mitral cells (M/TCs). Optogenetic activation of PPG neurons resulted in a mixed excitation and inhibition that created a multiphasic response shaping the M/TCs firing pattern. This suggests that PPG neurons could drive neuromodulation of the olfactory output and change the synaptic map regulating olfactory coding

Distributed organization of a brain microcircuit analyzed by three-dimensional modeling : the olfactory bulb

The functional consequences of the laminar organization observed in cortical systems cannot be easily studied using standard experimental techniques, abstract theoretical representations, or dimensionally reduced models built from scratch. To solve this problem we have developed a full implementation of an olfactory bulb microcircuit using realistic three-dimensional (3D) inputs, cell morphologies, and network connectivity. The results provide new insights into the relations between the functional properties of individual cells and the networks in which they are embedded. To our knowledge, this is the first model of the mitral-granule cell network to include a realistic representation of the experimentally-recorded complex spatial patterns elicited in the glomerular layer (GL) by natural odor stimulation. Although the olfactory bulb, due to its organization, has unique advantages with respect to other brain systems, the method is completely general, and can be integrated with more general approaches to other systems. The model makes experimentally testable predictions on distributed processing and on the differential backpropagation of somatic action potentials in each lateral dendrite following odor learning, providing a powerful 3D framework for investigating the functions of brain microcircuits