Viral tracing identifies distributed columnar organization in the olfactory bulb

Willhite, David C.; Nguyen, Katherine T.; Masurkar, Arjun V.; Greer, Charles A.; Shepherd, Gordon M.; Chen, Wei R.

doi:10.1073/pnas.0602032103

Cited by 157 publications

(160 citation statements)

References 50 publications

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“…By 5-6 dpi, the virus spread was apparent in deeper brain areas, including septal and preoptic nuclei, periventricular and paraventricular nuclei, the arcuate hypothalamic nucleus, the habenular nucleus, and hippocampus (data not shown). These observations demonstrate that VSV(LCMV-G) can travel several synaptic steps from peripheral ORNs to the higher olfactory centers in an anterograde direction, as judged by known circuitry, and contrasts with studies using retrograde viruses (22,24).…”

Section: Cell Biologymentioning

confidence: 58%

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Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors

Beier

Saunders

Oldenburg

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

161

198

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To understand how the nervous system processes information, a map of the connections among neurons would be of great benefit. Here we describe the use of vesicular stomatitis virus (VSV) for tracing neuronal connections in vivo. We made VSV vectors that used glycoprotein (G) genes from several other viruses. The G protein from lymphocytic choriomeningitis virus endowed VSV with the ability to spread transsynaptically, specifically in an anterograde direction, whereas the rabies virus glycoprotein gave a specifically retrograde transsynaptic pattern. The use of an avian G protein fusion allowed specific targeting of cells expressing an avian receptor, which allowed a demonstration of monosynaptic anterograde tracing from defined cells. Synaptic connectivity of pairs of virally labeled cells was demonstrated by using slice cultures and electrophysiology. In vivo infections of several areas in the mouse brain led to the predicted patterns of spread for anterograde or retrograde tracers.

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Section: Cell Biologymentioning

confidence: 58%

“…4A). The labeled PG cells and GCs often formed clusters, consistent with the columnar synaptic organization of the local connections in the OB (22). Some of the labeled GC clusters reached to the rostral end of rostral migratory stream (RMS; Fig.…”

Section: Cell Biologymentioning

confidence: 87%

Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors

Beier

Saunders

Oldenburg

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

161

198

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“…Single clusters in the olfactory bulb, obtained from a pseudorabies virus staining pattern after a single injection (6), are illustrated in Fig. 1A.…”

Section: Resultsmentioning

confidence: 99%

Synaptic clusters function as odor operators in the olfactory bulb

Migliore

Cavarretta

Marasco

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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How the olfactory bulb organizes and processes odor inputs through fundamental operations of its microcircuits is largely unknown. To gain new insight we focus on odor-activated synaptic clusters related to individual glomeruli, which we call glomerular units. Using a 3D model of mitral and granule cell interactions supported by experimental findings, combined with a matrix-based representation of glomerular operations, we identify the mechanisms for forming one or more glomerular units in response to a given odor, how and to what extent the glomerular units interfere or interact with each other during learning, their computational role within the olfactory bulb microcircuit, and how their actions can be formalized into a theoretical framework in which the olfactory bulb can be considered to contain "odor operators" unique to each individual. The results provide new and specific theoretical and experimentally testable predictions. T he organization of olfactory bulb network elements and their synaptic connectivity has evolved to subserve special computational functions needed for odor detection and recognition (1-5). Key to this organization are the olfactory glomeruli, collecting input from olfactory receptor neuron subsets. These connect to the dendrites of mitral, tufted, and periglomerular cells, and the mitral and tufted cells in turn connect to granule cells. We term these interconnected cells a cluster, and a cluster related to a given glomerulus is a glomerular unit (GU), often visualized as a column of granule cell bodies located below a glomerulus (6, 7). The existence of such GUs has also been suggested from 2-deoxyglucose (8) and voltage-sensitive dye studies (9).Understanding the neural basis of odor processing therefore requires understanding the computational functions and role of GUs. These issues, which are difficult or impossible in experiments, can be conveniently explored using realistic computational models, provided they are able to explain and reproduce crucial experimental findings on glomerular clusters or units.Analyzing synaptic interactions between cells with overlapping dendrites requires modeling in real 3D space. Scaling up to the network level further requires scaling up realistic structural and functional properties to many thousands of cells (10). Building on this unique approach, we show that this model generates columnar clusters of cells related to individual glomeruli, as in the experiments, and further demonstrates mechanisms of odor processing within and between the GUs. Finally, interpreting this network activity requires a theoretical framework, incorporating distributed activated glomeruli within the global network, for which we introduce the concept of the odor operator. The results provide a basis for extension to the glomerular level on the one hand and interactions with olfactory cortex on the other.

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“…Interestingly, mitral cell firing patterns are only controlled by a few glomeruli spatially distant and all lateral connections are not functionally equivalent (Fantana et al, 2008). The higher connectivity observed between some cells may be mediated by the widely dispersed granule cell columns, extending from the glomeruli to the deep GCL (Willhite et al, 2006). Backpropagation of action potentials in the lateral dendrites of mitral cells, together with granule cell actions on mitral cells within narrow columns forming glomerular units, may permit generation of strong local inhibition between distant mitral cells (Migliore and Shepherd, 2008).…”

Section: Early Sensory Information Processing In the Ob Circuitmentioning

confidence: 99%

Turnover of Newborn Olfactory Bulb Neurons Optimizes Olfaction

Mouret¹,

Lepousez²,

Gras³

et al. 2009

J. Neurosci.

125

111

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Postdevelopmental neurogenesis occurs in the olfactory bulb (OB), to which new interneurons are continuously recruited. However, only a subset of the adult-generated interneurons survives, as many undergo programmed cell death. As part of homeostatic processes, the removal of new neurons is required alongside the addition of new ones, to ensure a stable neuron number. In addition to a critical role in tissue maintenance, it is still unclear whether this neuronal elimination affects the functioning of adult circuits. Using focal drug delivery restricted to the OB, we investigated the significance of programmed cell death in the adult OB circuits. Cell death was effectively blocked by the broad-spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD). The zVAD effect differed with newborn interneuron location, either in the superficial (periglomerular cells) or in the deep (granule cells) OB layers. Furthermore, whereas sensory experience potentiated the effect of zVAD on the survival of new granule cells, it had no additional effect on the survival of new periglomerular cells. Thus, distinct mechanisms control the survival/elimination decision of newborn interneuron subtypes. However, zVAD had no effect on the olfactory sensory neurons projecting to the bulb. Remarkably, psychophysical analyzes revealed that a normal rate of new neuron elimination was essential for optimal odorant exploration and discrimination. This study highlights the importance of cell elimination for adjusting olfactory performance. We conclude that adult-generated OB interneurons are continually turned over, rather than simply added, and the precise balance between new and mature interneurons, set through active selection/ elimination processes, is essential for optimizing olfaction.

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Viral tracing identifies distributed columnar organization in the olfactory bulb

Cited by 157 publications

References 50 publications

Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors

Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors

Synaptic clusters function as odor operators in the olfactory bulb

Turnover of Newborn Olfactory Bulb Neurons Optimizes Olfaction

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