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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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Preferential integration of late-generated mitral cells into the ventrolateral portion of the developing olfactory bulb.(a–c) A coronal section of E15 olfactory bulb immunostained with IdU (red), CldU (green) and Tbr1 (blue) (a). IdU (b) and CldU (c) were injected into pregnant dam at E10 and E12, respectively. E10-generated mitral cells non-preferentially distribute within the MCL, while E12-generated mitral cells are preferentially localized at the ventrolateral portion; IZ: intermediate zone; VZ: ventricular zone. (d–g) Quantification of distribution of Tbr1+ cells generated at E10 (e), E11 (f), or E12 (g) in E15 olfactory bulb. Thymidine analogs (XdU) were injected at each time point. Six olfactory bulb sections (3 animals) were analyzed for each time points of generation. Each olfactory bulb section was radially-separated into twelve compartments (d), and the percentages of XdU+/Tbr1+ cells found in each compartment among total XdU+/Tbr1+ cells in the section are shown with rose graphs (e–g). A non-uniform distribution around the circle is found with E11- (p<0.001) and E12-generated mitral cells (p<0.001), but not with E10-generated mitral cells (p=0.258) (Rayleigh test). The population mean angle is shown with red bar in the graph only when non-uniform distribution around circle is found with Rayleigh test. Both E11- (p<0.001) and E12-generated mitral cells (p<0.001) preferentially distributed around the population mean angles (V-test, a modified Rayleigh test). Scale bars represent 100 μm.
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Figure 2: Preferential integration of late-generated mitral cells into the ventrolateral portion of the developing olfactory bulb.(a–c) A coronal section of E15 olfactory bulb immunostained with IdU (red), CldU (green) and Tbr1 (blue) (a). IdU (b) and CldU (c) were injected into pregnant dam at E10 and E12, respectively. E10-generated mitral cells non-preferentially distribute within the MCL, while E12-generated mitral cells are preferentially localized at the ventrolateral portion; IZ: intermediate zone; VZ: ventricular zone. (d–g) Quantification of distribution of Tbr1+ cells generated at E10 (e), E11 (f), or E12 (g) in E15 olfactory bulb. Thymidine analogs (XdU) were injected at each time point. Six olfactory bulb sections (3 animals) were analyzed for each time points of generation. Each olfactory bulb section was radially-separated into twelve compartments (d), and the percentages of XdU+/Tbr1+ cells found in each compartment among total XdU+/Tbr1+ cells in the section are shown with rose graphs (e–g). A non-uniform distribution around the circle is found with E11- (p<0.001) and E12-generated mitral cells (p<0.001), but not with E10-generated mitral cells (p=0.258) (Rayleigh test). The population mean angle is shown with red bar in the graph only when non-uniform distribution around circle is found with Rayleigh test. Both E11- (p<0.001) and E12-generated mitral cells (p<0.001) preferentially distributed around the population mean angles (V-test, a modified Rayleigh test). Scale bars represent 100 μm.

Mentions: An alternative hypothesis is that early- and late-generated mitral cells are fated to integrate specifically into the dorsomedial and ventrolateral portions of the olfactory bulb, respectively. Therefore, we examined the distribution of E10-, E11-, and E12-generated mitral cells at E15 (Fig. 2a). Tbr1 was used to identify mitral cells since not all express Tbx21 at E15. Most E10-generated mitral cells reached the nascent MCL by E15 (Fig. 2b). To quantify their distribution, the olfactory bulb was radially divided into twelve compartments and the percentages of XdU+/Tbr1+ cells in each compartment were calculated (Fig. 2d). Unexpectedly, E10-generated mitral cells were evenly distributed throughout the olfactory bulb, rather than preferentially in the dorsomedial portion (Fig. 2e). In contrast, larger numbers of E12-generated mitral cells was found in ventrolateral portion, although most were in the intermediate zone between the nascent MCL and ventricular zone (Fig. 2c,g). E11-generated mitral cells showed a distribution pattern intermediate between E10- and E12-generated cells (Fig. 2f). A Rayleigh test revealed that E10-generated mitral cells were uniformly distributed in the olfactory bulb at E15 (p=0.258). However, the distributions of E11- and E12-generated mitral cells were non-uniform (p<0.001 for both E11 and E12-generated mitral cells). The distribution peak of both E11- and E12-generated mitral cells were within the ventrolateral portion of the olfactory bulb. These results suggest that late-generated mitral cells preferentially integrate into the ventrolateral portion of the olfactory bulb, while early-generated mitral cells do not exhibit a preferential topographic integration. Therefore, the sparse density of E10-generated mitral cells in V-MCL may be attributed to the integration of larger numbers of E11- and E12-generated mitral cells. Likewise, the equal distribution of E11-generated mitral cells in D- and V-MCL found in P20 and P0 olfactory bulbs may reflect the integration of larger numbers of E12-generated mitral cells into V-MCL during continuing embryogenesis.


Timing of neurogenesis is a determinant of olfactory circuitry.

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

Preferential integration of late-generated mitral cells into the ventrolateral portion of the developing olfactory bulb.(a–c) A coronal section of E15 olfactory bulb immunostained with IdU (red), CldU (green) and Tbr1 (blue) (a). IdU (b) and CldU (c) were injected into pregnant dam at E10 and E12, respectively. E10-generated mitral cells non-preferentially distribute within the MCL, while E12-generated mitral cells are preferentially localized at the ventrolateral portion; IZ: intermediate zone; VZ: ventricular zone. (d–g) Quantification of distribution of Tbr1+ cells generated at E10 (e), E11 (f), or E12 (g) in E15 olfactory bulb. Thymidine analogs (XdU) were injected at each time point. Six olfactory bulb sections (3 animals) were analyzed for each time points of generation. Each olfactory bulb section was radially-separated into twelve compartments (d), and the percentages of XdU+/Tbr1+ cells found in each compartment among total XdU+/Tbr1+ cells in the section are shown with rose graphs (e–g). A non-uniform distribution around the circle is found with E11- (p<0.001) and E12-generated mitral cells (p<0.001), but not with E10-generated mitral cells (p=0.258) (Rayleigh test). The population mean angle is shown with red bar in the graph only when non-uniform distribution around circle is found with Rayleigh test. Both E11- (p<0.001) and E12-generated mitral cells (p<0.001) preferentially distributed around the population mean angles (V-test, a modified Rayleigh test). Scale bars represent 100 μm.
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Figure 2: Preferential integration of late-generated mitral cells into the ventrolateral portion of the developing olfactory bulb.(a–c) A coronal section of E15 olfactory bulb immunostained with IdU (red), CldU (green) and Tbr1 (blue) (a). IdU (b) and CldU (c) were injected into pregnant dam at E10 and E12, respectively. E10-generated mitral cells non-preferentially distribute within the MCL, while E12-generated mitral cells are preferentially localized at the ventrolateral portion; IZ: intermediate zone; VZ: ventricular zone. (d–g) Quantification of distribution of Tbr1+ cells generated at E10 (e), E11 (f), or E12 (g) in E15 olfactory bulb. Thymidine analogs (XdU) were injected at each time point. Six olfactory bulb sections (3 animals) were analyzed for each time points of generation. Each olfactory bulb section was radially-separated into twelve compartments (d), and the percentages of XdU+/Tbr1+ cells found in each compartment among total XdU+/Tbr1+ cells in the section are shown with rose graphs (e–g). A non-uniform distribution around the circle is found with E11- (p<0.001) and E12-generated mitral cells (p<0.001), but not with E10-generated mitral cells (p=0.258) (Rayleigh test). The population mean angle is shown with red bar in the graph only when non-uniform distribution around circle is found with Rayleigh test. Both E11- (p<0.001) and E12-generated mitral cells (p<0.001) preferentially distributed around the population mean angles (V-test, a modified Rayleigh test). Scale bars represent 100 μm.
Mentions: An alternative hypothesis is that early- and late-generated mitral cells are fated to integrate specifically into the dorsomedial and ventrolateral portions of the olfactory bulb, respectively. Therefore, we examined the distribution of E10-, E11-, and E12-generated mitral cells at E15 (Fig. 2a). Tbr1 was used to identify mitral cells since not all express Tbx21 at E15. Most E10-generated mitral cells reached the nascent MCL by E15 (Fig. 2b). To quantify their distribution, the olfactory bulb was radially divided into twelve compartments and the percentages of XdU+/Tbr1+ cells in each compartment were calculated (Fig. 2d). Unexpectedly, E10-generated mitral cells were evenly distributed throughout the olfactory bulb, rather than preferentially in the dorsomedial portion (Fig. 2e). In contrast, larger numbers of E12-generated mitral cells was found in ventrolateral portion, although most were in the intermediate zone between the nascent MCL and ventricular zone (Fig. 2c,g). E11-generated mitral cells showed a distribution pattern intermediate between E10- and E12-generated cells (Fig. 2f). A Rayleigh test revealed that E10-generated mitral cells were uniformly distributed in the olfactory bulb at E15 (p=0.258). However, the distributions of E11- and E12-generated mitral cells were non-uniform (p<0.001 for both E11 and E12-generated mitral cells). The distribution peak of both E11- and E12-generated mitral cells were within the ventrolateral portion of the olfactory bulb. These results suggest that late-generated mitral cells preferentially integrate into the ventrolateral portion of the olfactory bulb, while early-generated mitral cells do not exhibit a preferential topographic integration. Therefore, the sparse density of E10-generated mitral cells in V-MCL may be attributed to the integration of larger numbers of E11- and E12-generated mitral cells. Likewise, the equal distribution of E11-generated mitral cells in D- and V-MCL found in P20 and P0 olfactory bulbs may reflect the integration of larger numbers of E12-generated mitral cells into V-MCL during continuing embryogenesis.

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