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Timing of neurogenesis is a determinant of olfactory circuitry.

Imamura F, Ayoub AE, Rakic P, Greer CA - Nat. Neurosci. (2011)

Bottom Line: In addition, the late-generated mitral cells extended substantially stronger projections to the olfactory tubercle than did the early-generated cells.Together, these data indicate that the odorant receptor map is developmentally linked to the olfactory cortices in part by the birthdate of mitral cells.Thus, different olfactory cortical regions become involved in processing information from distinct regions of the odorant receptor map.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA.

ABSTRACT
An odorant receptor map in mammals that is constructed by the glomerular coalescence of sensory neuron axons in the olfactory bulb is essential for proper odor information processing. How this map is linked with olfactory cortex is unknown. Using a battery of methods, including various markers of cell division in combination with tracers of neuronal connections and time-lapse live imaging, we found that early- and late-generated mouse mitral cells became differentially distributed in the dorsal and ventral subdivisions of the odorant receptor map. In addition, the late-generated mitral cells extended substantially stronger projections to the olfactory tubercle than did the early-generated cells. Together, these data indicate that the odorant receptor map is developmentally linked to the olfactory cortices in part by the birthdate of mitral cells. Thus, different olfactory cortical regions become involved in processing information from distinct regions of the odorant receptor map.

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Related in: MedlinePlus

Tangential migration of late-generated mitral cells in the developing olfactory bulb.(a,b,d,e) Coronal sections of E13 (a,b) and E14 (d,e) olfactory bulbs in which E12-generated cells were labeled with BrdU (green). Radial glial processes were immunostained with RC2 (b,e; red). (c,f) Quantification of BrdU+ cell distributions in E13 (c) and E14 (f) olfactory bulb sections with the method described in Figure 2d. A non-uniform distribution of E12-generated cells was found at both E13 (p<0.001; n=6 olfactory bulbs) and E14 (p<0.001; n=6) (Rayleigh test). The population mean angle (red bar) is seen in dorsolateral region at E13, while it is shifted to lateral region at E14. At both E13 (p<0.001) and E14 (p<0.001), E12-generated cells were preferentially distributed around the population mean angles (V-test). (g,h) Horizontal section of E14 DCX-GFP mouse olfactory bulb immunostained with BrdU (red) and Tbr1 (blue). BrdU labels E12-generated cells. GFP+ cells in the intermediate zone have a tangentially elongated morphology. BrdU+ or Tbr1+ cells are mostly GFP+, and triple-labeled cells are also found in the slice (h). (i) Time-lapse imaging of acute DCX-GFP E14 mouse olfactory bulb slice was carried out to determine the mode of migration of GFP+ cells. A z-stack projection was prepared to track cell movement in different planes. The arrows show the progression of a GFP+ cell toward the posterior portion of the olfactory bulb. (j) A single optical slice shows that the GFP+ cell observed in (i) expresses Tbr1 (red). Scale bars represent 100μm (a,d,g) and 20μm (b,e,h,j).
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Figure 3: Tangential migration of late-generated mitral cells in the developing olfactory bulb.(a,b,d,e) Coronal sections of E13 (a,b) and E14 (d,e) olfactory bulbs in which E12-generated cells were labeled with BrdU (green). Radial glial processes were immunostained with RC2 (b,e; red). (c,f) Quantification of BrdU+ cell distributions in E13 (c) and E14 (f) olfactory bulb sections with the method described in Figure 2d. A non-uniform distribution of E12-generated cells was found at both E13 (p<0.001; n=6 olfactory bulbs) and E14 (p<0.001; n=6) (Rayleigh test). The population mean angle (red bar) is seen in dorsolateral region at E13, while it is shifted to lateral region at E14. At both E13 (p<0.001) and E14 (p<0.001), E12-generated cells were preferentially distributed around the population mean angles (V-test). (g,h) Horizontal section of E14 DCX-GFP mouse olfactory bulb immunostained with BrdU (red) and Tbr1 (blue). BrdU labels E12-generated cells. GFP+ cells in the intermediate zone have a tangentially elongated morphology. BrdU+ or Tbr1+ cells are mostly GFP+, and triple-labeled cells are also found in the slice (h). (i) Time-lapse imaging of acute DCX-GFP E14 mouse olfactory bulb slice was carried out to determine the mode of migration of GFP+ cells. A z-stack projection was prepared to track cell movement in different planes. The arrows show the progression of a GFP+ cell toward the posterior portion of the olfactory bulb. (j) A single optical slice shows that the GFP+ cell observed in (i) expresses Tbr1 (red). Scale bars represent 100μm (a,d,g) and 20μm (b,e,h,j).

Mentions: What is the underlying mechanism for the specific targeting of late-generated mitral cells to the V-MCL of olfactory bulb? Because mitral cell precursors are first generated in the ventricular zone of the presumptive olfactory bulb30, we examined whether more mitral cells are generated in the ventrolateral ventricular zone. To test this, E12-generated cells were labeled with BrdU, and their distributions were examined at E13 and E14. At E13 most BrdU+ cells were found in the ventricular zone (Fig. 3a); the nuclei of these cells were radially elongated and parallel to the processes of radial glia (RC2+) (Fig. 3b), suggesting they were migrating radially from the ventricular zone toward the intermediate zone. However, a preferential distribution in the ventrolateral portion was not detected. The distribution was quantified as described above, but all BrdU+ cells in the olfactory bulb were included because it was too early to use Tbr1 expression to identify the E12-generated mitral cells. Despite the non-uniform distribution of E12-generated cells in E13 olfactory bulb (p<0.001), their distribution peak was in the dorsolateral portion (Fig. 3c). At E14, many BrdU+ cells with tangentially elongated nuclei were found in the intermediate zone (Fig. 3d,e). The distribution peak of E12-generated cells in the olfactory bulb also shifted from dorsolateral to lateral (Fig. 3f). Moreover, when the distributions of E12-generated cells were separately analyzed in the anterior and posterior regions of E13 and E14 olfactory bulbs, the percentage of cells found in the ventrolateral portion was higher in the posterior than anterior (Supplementary Fig. 5). From these observations, we propose a hypothesis that E12-generated cells migrate tangentially in the intermediate zone toward the postero-ventro-lateral region of the olfactory bulb. It was noted previously from Golgi-stained and DiI-labeled tissues that mitral cells in the intermediate zone have a tangential-like morphology30, but their organization and the underlying reason for the change from radial to tangential was unknown. We suggest that tangentially elongated cells within the intermediate zone are migrating late-generated mitral cells.


Timing of neurogenesis is a determinant of olfactory circuitry.

Imamura F, Ayoub AE, Rakic P, Greer CA - Nat. Neurosci. (2011)

Tangential migration of late-generated mitral cells in the developing olfactory bulb.(a,b,d,e) Coronal sections of E13 (a,b) and E14 (d,e) olfactory bulbs in which E12-generated cells were labeled with BrdU (green). Radial glial processes were immunostained with RC2 (b,e; red). (c,f) Quantification of BrdU+ cell distributions in E13 (c) and E14 (f) olfactory bulb sections with the method described in Figure 2d. A non-uniform distribution of E12-generated cells was found at both E13 (p<0.001; n=6 olfactory bulbs) and E14 (p<0.001; n=6) (Rayleigh test). The population mean angle (red bar) is seen in dorsolateral region at E13, while it is shifted to lateral region at E14. At both E13 (p<0.001) and E14 (p<0.001), E12-generated cells were preferentially distributed around the population mean angles (V-test). (g,h) Horizontal section of E14 DCX-GFP mouse olfactory bulb immunostained with BrdU (red) and Tbr1 (blue). BrdU labels E12-generated cells. GFP+ cells in the intermediate zone have a tangentially elongated morphology. BrdU+ or Tbr1+ cells are mostly GFP+, and triple-labeled cells are also found in the slice (h). (i) Time-lapse imaging of acute DCX-GFP E14 mouse olfactory bulb slice was carried out to determine the mode of migration of GFP+ cells. A z-stack projection was prepared to track cell movement in different planes. The arrows show the progression of a GFP+ cell toward the posterior portion of the olfactory bulb. (j) A single optical slice shows that the GFP+ cell observed in (i) expresses Tbr1 (red). Scale bars represent 100μm (a,d,g) and 20μm (b,e,h,j).
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Figure 3: Tangential migration of late-generated mitral cells in the developing olfactory bulb.(a,b,d,e) Coronal sections of E13 (a,b) and E14 (d,e) olfactory bulbs in which E12-generated cells were labeled with BrdU (green). Radial glial processes were immunostained with RC2 (b,e; red). (c,f) Quantification of BrdU+ cell distributions in E13 (c) and E14 (f) olfactory bulb sections with the method described in Figure 2d. A non-uniform distribution of E12-generated cells was found at both E13 (p<0.001; n=6 olfactory bulbs) and E14 (p<0.001; n=6) (Rayleigh test). The population mean angle (red bar) is seen in dorsolateral region at E13, while it is shifted to lateral region at E14. At both E13 (p<0.001) and E14 (p<0.001), E12-generated cells were preferentially distributed around the population mean angles (V-test). (g,h) Horizontal section of E14 DCX-GFP mouse olfactory bulb immunostained with BrdU (red) and Tbr1 (blue). BrdU labels E12-generated cells. GFP+ cells in the intermediate zone have a tangentially elongated morphology. BrdU+ or Tbr1+ cells are mostly GFP+, and triple-labeled cells are also found in the slice (h). (i) Time-lapse imaging of acute DCX-GFP E14 mouse olfactory bulb slice was carried out to determine the mode of migration of GFP+ cells. A z-stack projection was prepared to track cell movement in different planes. The arrows show the progression of a GFP+ cell toward the posterior portion of the olfactory bulb. (j) A single optical slice shows that the GFP+ cell observed in (i) expresses Tbr1 (red). Scale bars represent 100μm (a,d,g) and 20μm (b,e,h,j).
Mentions: What is the underlying mechanism for the specific targeting of late-generated mitral cells to the V-MCL of olfactory bulb? Because mitral cell precursors are first generated in the ventricular zone of the presumptive olfactory bulb30, we examined whether more mitral cells are generated in the ventrolateral ventricular zone. To test this, E12-generated cells were labeled with BrdU, and their distributions were examined at E13 and E14. At E13 most BrdU+ cells were found in the ventricular zone (Fig. 3a); the nuclei of these cells were radially elongated and parallel to the processes of radial glia (RC2+) (Fig. 3b), suggesting they were migrating radially from the ventricular zone toward the intermediate zone. However, a preferential distribution in the ventrolateral portion was not detected. The distribution was quantified as described above, but all BrdU+ cells in the olfactory bulb were included because it was too early to use Tbr1 expression to identify the E12-generated mitral cells. Despite the non-uniform distribution of E12-generated cells in E13 olfactory bulb (p<0.001), their distribution peak was in the dorsolateral portion (Fig. 3c). At E14, many BrdU+ cells with tangentially elongated nuclei were found in the intermediate zone (Fig. 3d,e). The distribution peak of E12-generated cells in the olfactory bulb also shifted from dorsolateral to lateral (Fig. 3f). Moreover, when the distributions of E12-generated cells were separately analyzed in the anterior and posterior regions of E13 and E14 olfactory bulbs, the percentage of cells found in the ventrolateral portion was higher in the posterior than anterior (Supplementary Fig. 5). From these observations, we propose a hypothesis that E12-generated cells migrate tangentially in the intermediate zone toward the postero-ventro-lateral region of the olfactory bulb. It was noted previously from Golgi-stained and DiI-labeled tissues that mitral cells in the intermediate zone have a tangential-like morphology30, but their organization and the underlying reason for the change from radial to tangential was unknown. We suggest that tangentially elongated cells within the intermediate zone are migrating late-generated mitral cells.

Bottom Line: In addition, the late-generated mitral cells extended substantially stronger projections to the olfactory tubercle than did the early-generated cells.Together, these data indicate that the odorant receptor map is developmentally linked to the olfactory cortices in part by the birthdate of mitral cells.Thus, different olfactory cortical regions become involved in processing information from distinct regions of the odorant receptor map.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA.

ABSTRACT
An odorant receptor map in mammals that is constructed by the glomerular coalescence of sensory neuron axons in the olfactory bulb is essential for proper odor information processing. How this map is linked with olfactory cortex is unknown. Using a battery of methods, including various markers of cell division in combination with tracers of neuronal connections and time-lapse live imaging, we found that early- and late-generated mouse mitral cells became differentially distributed in the dorsal and ventral subdivisions of the odorant receptor map. In addition, the late-generated mitral cells extended substantially stronger projections to the olfactory tubercle than did the early-generated cells. Together, these data indicate that the odorant receptor map is developmentally linked to the olfactory cortices in part by the birthdate of mitral cells. Thus, different olfactory cortical regions become involved in processing information from distinct regions of the odorant receptor map.

Show MeSH
Related in: MedlinePlus