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Comprehensive connectivity of the mouse main olfactory bulb: analysis and online digital atlas.

Hintiryan H, Gou L, Zingg B, Yamashita S, Lyden HM, Song MY, Grewal AK, Zhang X, Toga AW, Dong HW - Front Neuroanat (2012)

Bottom Line: To facilitate use of the data, raw images are made publicly accessible through our online interactive visualization tool, the iConnectome, where users can view and annotate the high-resolution, multi-fluorescent connectivity data (www.MouseConnectome.org).Additional MOB injections and injections of the accessory olfactory bulb (AOB), anterior olfactory nucleus (AON), and other olfactory cortical areas gradually will be made available.Analysis of connections from different regions of the MOB revealed a novel, topographically arranged MOB projection roadmap, demonstrated disparate MOB connectivity with anterior versus posterior piriform cortical area (PIR), and exposed some novel aspects of well-established cortical olfactory projections.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles Los Angeles, CA, USA.

ABSTRACT
We introduce the first open resource for mouse olfactory connectivity data produced as part of the Mouse Connectome Project (MCP) at UCLA. The MCP aims to assemble a whole-brain connectivity atlas for the C57Bl/6J mouse using a double coinjection tracing method. Each coinjection consists of one anterograde and one retrograde tracer, which affords the advantage of simultaneously identifying efferent and afferent pathways and directly identifying reciprocal connectivity of injection sites. The systematic application of double coinjections potentially reveals interaction stations between injections and allows for the study of connectivity at the network level. To facilitate use of the data, raw images are made publicly accessible through our online interactive visualization tool, the iConnectome, where users can view and annotate the high-resolution, multi-fluorescent connectivity data (www.MouseConnectome.org). Systematic double coinjections were made into different regions of the main olfactory bulb (MOB) and data from 18 MOB cases (~72 pathways; 36 efferent/36 afferent) currently are available to view in iConnectome within their corresponding atlas level and their own bright-field cytoarchitectural background. Additional MOB injections and injections of the accessory olfactory bulb (AOB), anterior olfactory nucleus (AON), and other olfactory cortical areas gradually will be made available. Analysis of connections from different regions of the MOB revealed a novel, topographically arranged MOB projection roadmap, demonstrated disparate MOB connectivity with anterior versus posterior piriform cortical area (PIR), and exposed some novel aspects of well-established cortical olfactory projections.

No MeSH data available.


Related in: MedlinePlus

Non-overlapping double coinjections of PHAL/CTb in ACAd and BDA in MOp on bright-field Nissl background (A) directly reveal topography in both gray (AMd and RT) and white matter (int; B). White arrow indicates PHAL fibers (as dots) traveling ventral to BDA fibers in int(B). Injections (C–E) also reveal long projections pathways as demonstrated by PHAL fibers from the VISC crossing the corpus callosum and terminating in the contralateral mirror VISC area also labeled with CTb neurons (C; white arrow magnified in F). Overlapping PHAL and CTb (C,F) labeling suggests reciprocal connectivity between the mirrored structures. Image with the VISC and SSp injections in (C) is exposed to reveal fine fibers (blue and white arrows) that would otherwise not be visible if adjusted for the injection. Although PHAL and CTb injections look large, their actual size is ~300 μm in diameter (D,E). Possible interaction stations between the two injections sites (C) is indicated by PHAL fibers from VISC overlapping with FG back-labeled neurons from SSp within the supplementary somatosensory area (SSs) suggesting a VISC→SSs→SSp connectivity chain. Inter-regional connectivity is corroborated by cross validation of data (H–K). PHAL injection in SSp (H) labels terminals in MOp (I). FG injection in the same MOp site as PHAL-labeled terminals (K) layer-specifically back-labels neurons in SSp (J), precisely in SSp PHAL injection area (H). Scale bar, 1 mm (A,C); 200 μm (B,D–G); 500 μm (H–K). Case numbers SW110323-02A (A,B); SW101014-04A (C–G); SW110419-03A (H,I); SW110323-02A (J,K). Abbreviations: VISC, visceral area; SSp, primary somatosensory area; SSs, supplemental somatosensory area; MOp, primary motor area; AMd, dorsal anteromedial thalamic nucleus; RT, reticular nucleus of thalamus; int, internal capsule.
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Figure 2: Non-overlapping double coinjections of PHAL/CTb in ACAd and BDA in MOp on bright-field Nissl background (A) directly reveal topography in both gray (AMd and RT) and white matter (int; B). White arrow indicates PHAL fibers (as dots) traveling ventral to BDA fibers in int(B). Injections (C–E) also reveal long projections pathways as demonstrated by PHAL fibers from the VISC crossing the corpus callosum and terminating in the contralateral mirror VISC area also labeled with CTb neurons (C; white arrow magnified in F). Overlapping PHAL and CTb (C,F) labeling suggests reciprocal connectivity between the mirrored structures. Image with the VISC and SSp injections in (C) is exposed to reveal fine fibers (blue and white arrows) that would otherwise not be visible if adjusted for the injection. Although PHAL and CTb injections look large, their actual size is ~300 μm in diameter (D,E). Possible interaction stations between the two injections sites (C) is indicated by PHAL fibers from VISC overlapping with FG back-labeled neurons from SSp within the supplementary somatosensory area (SSs) suggesting a VISC→SSs→SSp connectivity chain. Inter-regional connectivity is corroborated by cross validation of data (H–K). PHAL injection in SSp (H) labels terminals in MOp (I). FG injection in the same MOp site as PHAL-labeled terminals (K) layer-specifically back-labels neurons in SSp (J), precisely in SSp PHAL injection area (H). Scale bar, 1 mm (A,C); 200 μm (B,D–G); 500 μm (H–K). Case numbers SW110323-02A (A,B); SW101014-04A (C–G); SW110419-03A (H,I); SW110323-02A (J,K). Abbreviations: VISC, visceral area; SSp, primary somatosensory area; SSs, supplemental somatosensory area; MOp, primary motor area; AMd, dorsal anteromedial thalamic nucleus; RT, reticular nucleus of thalamus; int, internal capsule.

Mentions: The Mouse Connectome Project (MCP) at UCLA aims to generate a connectivity map of the mouse brain using a double coinjection tracing strategy, which was first reported for studying neuronal connectivity in the rat (Thompson and Swanson, 2010). Each of the two non-overlapping coinjections consists of one anterograde and one retrograde tracer. Phaseolus vulgaris-leucoagglutinin (PHAL: anterograde: green) is coinjected with cholera toxin subunit b (CTb: retrograde: magenta) while biotinylated dextran amine (BDA: anterograde: red) is coinjected with Fluorogold (FG: retrograde: gold) (Figure 2A). These double coinjections allow concurrent examination of input and output pathways from each injection and yield four times the amount of data collected from classic single tracer injections, reducing cost, processing time, and number of animals used. Coinjections also expose topographically distinct connectional patterns associated with the two injections within the same brain (Figure 2B), increasing the precision of a connectome map. Further, unlike MacroConnectomes that utilize in vivo diffusion tractography imaging to map fiber tracts (Behrens and Sporns, 2012; Cammoun et al., 2012; Van Essen et al., 2012) and MicroConnectomes (or synaptomes) (Lichtman et al., 2008; Micheva et al., 2010; Bock et al., 2011; Briggman et al., 2011) that map local circuits or synaptic connectivity at single neuron level, our approach concurrently reveals long projection pathways (Figures 2C,H–K) and inter-regional connectivity (Figures 2H–K). These inter-regional connections can be recurrent (reciprocal) connections (Figures 2C,F) and/or interaction stations (Figure 2G). Reciprocal connections between the injection sites and other structures are indicated by overlapping PHAL-labeled terminals and CTb-labeled neurons (Figures 2C,F) or by BDA terminals overlapping with FG-labeled neurons. Potential interaction stations between injection sites are demonstrated by PHAL-fiber innervation of FG-labeled neurons (Figure 2G) or BDA innervation of CTb-labeled neurons.


Comprehensive connectivity of the mouse main olfactory bulb: analysis and online digital atlas.

Hintiryan H, Gou L, Zingg B, Yamashita S, Lyden HM, Song MY, Grewal AK, Zhang X, Toga AW, Dong HW - Front Neuroanat (2012)

Non-overlapping double coinjections of PHAL/CTb in ACAd and BDA in MOp on bright-field Nissl background (A) directly reveal topography in both gray (AMd and RT) and white matter (int; B). White arrow indicates PHAL fibers (as dots) traveling ventral to BDA fibers in int(B). Injections (C–E) also reveal long projections pathways as demonstrated by PHAL fibers from the VISC crossing the corpus callosum and terminating in the contralateral mirror VISC area also labeled with CTb neurons (C; white arrow magnified in F). Overlapping PHAL and CTb (C,F) labeling suggests reciprocal connectivity between the mirrored structures. Image with the VISC and SSp injections in (C) is exposed to reveal fine fibers (blue and white arrows) that would otherwise not be visible if adjusted for the injection. Although PHAL and CTb injections look large, their actual size is ~300 μm in diameter (D,E). Possible interaction stations between the two injections sites (C) is indicated by PHAL fibers from VISC overlapping with FG back-labeled neurons from SSp within the supplementary somatosensory area (SSs) suggesting a VISC→SSs→SSp connectivity chain. Inter-regional connectivity is corroborated by cross validation of data (H–K). PHAL injection in SSp (H) labels terminals in MOp (I). FG injection in the same MOp site as PHAL-labeled terminals (K) layer-specifically back-labels neurons in SSp (J), precisely in SSp PHAL injection area (H). Scale bar, 1 mm (A,C); 200 μm (B,D–G); 500 μm (H–K). Case numbers SW110323-02A (A,B); SW101014-04A (C–G); SW110419-03A (H,I); SW110323-02A (J,K). Abbreviations: VISC, visceral area; SSp, primary somatosensory area; SSs, supplemental somatosensory area; MOp, primary motor area; AMd, dorsal anteromedial thalamic nucleus; RT, reticular nucleus of thalamus; int, internal capsule.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3412993&req=5

Figure 2: Non-overlapping double coinjections of PHAL/CTb in ACAd and BDA in MOp on bright-field Nissl background (A) directly reveal topography in both gray (AMd and RT) and white matter (int; B). White arrow indicates PHAL fibers (as dots) traveling ventral to BDA fibers in int(B). Injections (C–E) also reveal long projections pathways as demonstrated by PHAL fibers from the VISC crossing the corpus callosum and terminating in the contralateral mirror VISC area also labeled with CTb neurons (C; white arrow magnified in F). Overlapping PHAL and CTb (C,F) labeling suggests reciprocal connectivity between the mirrored structures. Image with the VISC and SSp injections in (C) is exposed to reveal fine fibers (blue and white arrows) that would otherwise not be visible if adjusted for the injection. Although PHAL and CTb injections look large, their actual size is ~300 μm in diameter (D,E). Possible interaction stations between the two injections sites (C) is indicated by PHAL fibers from VISC overlapping with FG back-labeled neurons from SSp within the supplementary somatosensory area (SSs) suggesting a VISC→SSs→SSp connectivity chain. Inter-regional connectivity is corroborated by cross validation of data (H–K). PHAL injection in SSp (H) labels terminals in MOp (I). FG injection in the same MOp site as PHAL-labeled terminals (K) layer-specifically back-labels neurons in SSp (J), precisely in SSp PHAL injection area (H). Scale bar, 1 mm (A,C); 200 μm (B,D–G); 500 μm (H–K). Case numbers SW110323-02A (A,B); SW101014-04A (C–G); SW110419-03A (H,I); SW110323-02A (J,K). Abbreviations: VISC, visceral area; SSp, primary somatosensory area; SSs, supplemental somatosensory area; MOp, primary motor area; AMd, dorsal anteromedial thalamic nucleus; RT, reticular nucleus of thalamus; int, internal capsule.
Mentions: The Mouse Connectome Project (MCP) at UCLA aims to generate a connectivity map of the mouse brain using a double coinjection tracing strategy, which was first reported for studying neuronal connectivity in the rat (Thompson and Swanson, 2010). Each of the two non-overlapping coinjections consists of one anterograde and one retrograde tracer. Phaseolus vulgaris-leucoagglutinin (PHAL: anterograde: green) is coinjected with cholera toxin subunit b (CTb: retrograde: magenta) while biotinylated dextran amine (BDA: anterograde: red) is coinjected with Fluorogold (FG: retrograde: gold) (Figure 2A). These double coinjections allow concurrent examination of input and output pathways from each injection and yield four times the amount of data collected from classic single tracer injections, reducing cost, processing time, and number of animals used. Coinjections also expose topographically distinct connectional patterns associated with the two injections within the same brain (Figure 2B), increasing the precision of a connectome map. Further, unlike MacroConnectomes that utilize in vivo diffusion tractography imaging to map fiber tracts (Behrens and Sporns, 2012; Cammoun et al., 2012; Van Essen et al., 2012) and MicroConnectomes (or synaptomes) (Lichtman et al., 2008; Micheva et al., 2010; Bock et al., 2011; Briggman et al., 2011) that map local circuits or synaptic connectivity at single neuron level, our approach concurrently reveals long projection pathways (Figures 2C,H–K) and inter-regional connectivity (Figures 2H–K). These inter-regional connections can be recurrent (reciprocal) connections (Figures 2C,F) and/or interaction stations (Figure 2G). Reciprocal connections between the injection sites and other structures are indicated by overlapping PHAL-labeled terminals and CTb-labeled neurons (Figures 2C,F) or by BDA terminals overlapping with FG-labeled neurons. Potential interaction stations between injection sites are demonstrated by PHAL-fiber innervation of FG-labeled neurons (Figure 2G) or BDA innervation of CTb-labeled neurons.

Bottom Line: To facilitate use of the data, raw images are made publicly accessible through our online interactive visualization tool, the iConnectome, where users can view and annotate the high-resolution, multi-fluorescent connectivity data (www.MouseConnectome.org).Additional MOB injections and injections of the accessory olfactory bulb (AOB), anterior olfactory nucleus (AON), and other olfactory cortical areas gradually will be made available.Analysis of connections from different regions of the MOB revealed a novel, topographically arranged MOB projection roadmap, demonstrated disparate MOB connectivity with anterior versus posterior piriform cortical area (PIR), and exposed some novel aspects of well-established cortical olfactory projections.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles Los Angeles, CA, USA.

ABSTRACT
We introduce the first open resource for mouse olfactory connectivity data produced as part of the Mouse Connectome Project (MCP) at UCLA. The MCP aims to assemble a whole-brain connectivity atlas for the C57Bl/6J mouse using a double coinjection tracing method. Each coinjection consists of one anterograde and one retrograde tracer, which affords the advantage of simultaneously identifying efferent and afferent pathways and directly identifying reciprocal connectivity of injection sites. The systematic application of double coinjections potentially reveals interaction stations between injections and allows for the study of connectivity at the network level. To facilitate use of the data, raw images are made publicly accessible through our online interactive visualization tool, the iConnectome, where users can view and annotate the high-resolution, multi-fluorescent connectivity data (www.MouseConnectome.org). Systematic double coinjections were made into different regions of the main olfactory bulb (MOB) and data from 18 MOB cases (~72 pathways; 36 efferent/36 afferent) currently are available to view in iConnectome within their corresponding atlas level and their own bright-field cytoarchitectural background. Additional MOB injections and injections of the accessory olfactory bulb (AOB), anterior olfactory nucleus (AON), and other olfactory cortical areas gradually will be made available. Analysis of connections from different regions of the MOB revealed a novel, topographically arranged MOB projection roadmap, demonstrated disparate MOB connectivity with anterior versus posterior piriform cortical area (PIR), and exposed some novel aspects of well-established cortical olfactory projections.

No MeSH data available.


Related in: MedlinePlus