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Maintenance of neuronal size gradient in MNTB requires sound-evoked activity

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ABSTRACT

Neurons of the medial nucleus of the trapezoid body (MNTB) act as fast-spiking inhibitory interneurons within the auditory brain stem. The MNTB is topographically organized, with low sound frequencies encoded laterally and high frequencies medially. We discovered a cell size gradient along this axis: lateral neurons are larger than medial neurons. The absence of this gradient in deaf mice lacking plasma membrane calcium ATPase 2 suggests an activity-dependent, calcium-mediated mechanism that controls neuronal soma size.

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Medial-to-lateral soma size gradient in the MNTB is absent in dfw2J mutants. A: cells were defined as medial if located in the medial third of the MNTB or lateral if located in the lateral third of the MNTB. B: there was a significant increase in the size of lateral cells compared with medial cells in the wild-type animals (*P ≤ 0.001). There was no significant increase in the size of lateral cells in +/dfw2J, dfw/dfw, dfw2J/dfw2J, or DTR mice. Error bars show SE. C: individual average cell size for medial and lateral cells in each MNTB. D: scatterplot of location along the tonotopic axis vs. cross-sectional surface area for 1 MNTB from a wild-type and a dfw2J/dfw2J mouse. The linear regression is significantly different from zero for wild type (P = 0.01) but not for dfw2J/dfw2J.
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Figure 3: Medial-to-lateral soma size gradient in the MNTB is absent in dfw2J mutants. A: cells were defined as medial if located in the medial third of the MNTB or lateral if located in the lateral third of the MNTB. B: there was a significant increase in the size of lateral cells compared with medial cells in the wild-type animals (*P ≤ 0.001). There was no significant increase in the size of lateral cells in +/dfw2J, dfw/dfw, dfw2J/dfw2J, or DTR mice. Error bars show SE. C: individual average cell size for medial and lateral cells in each MNTB. D: scatterplot of location along the tonotopic axis vs. cross-sectional surface area for 1 MNTB from a wild-type and a dfw2J/dfw2J mouse. The linear regression is significantly different from zero for wild type (P = 0.01) but not for dfw2J/dfw2J.

Mentions: MNTB neurons were significantly smaller in dfw2J/dfw2J (128.36 ± 7.54 μm2) than in WT (151.89 ± 1.11 μm2; Fig. 2, C and F; F = 5.894; P = 0.04). To determine whether these differences showed any tonotopic relationship, the nucleus was divided into thirds and neurons were assigned to medial, central, and lateral groups (Fig. 3A). We defined PMCA2 function as the percentage of PMCA2 protein, determined by the number of functional alleles possessed by an animal, multiplied by the PMCA2 pumping efficiency, determined by biochemical assay (Penheiter et al. 2001) and compared to WT. We tested a range of PMCA2 function from WT (which have 100% protein), +/dfw2J with ∼50% protein, dfw/dfw with ∼30% function as measured by a calcium clearance assay (Penheiter et al. 2001), and dfw2J/dfw2J, which have no functional PCMA2 protein (Table 1). In WT animals, medial neurons were significantly smaller (136.01 ± 2.66 μm2) than lateral neurons (157.71 ± 5.05 μm2; Fig. 3B; P = 0.02). In +/dfw2J, the location-dependent difference in neuronal cell size was decreased and no longer significant (Fig. 3B; P = 0.08). The size difference was decreased further in dfw/dfw and was absent in the dfw2J/dfw2J mice (Fig. 3B). Although absolute neuronal soma size varied slightly between animals, comparing the size difference in medial and lateral neurons for each individual mouse confirmed the presence or absence of the overall size gradient in the different genotypes (Fig. 3C). Neuronal soma size data of all measured individual neurons from one WT MNTB and one dfw2J/dfw2J MNTB are shown as an example in Fig. 3D. The slope of the linear regression for neuronal soma size is significantly nonzero in WT mice (Fig. 3D; P = 0.01), while no relationship between neuronal soma size and tonotopic location was found in dfw2J/dfw2J, demonstrating that there is a neuronal cell size gradient in WT that is absent in dfw2J/dfw2J.


Maintenance of neuronal size gradient in MNTB requires sound-evoked activity
Medial-to-lateral soma size gradient in the MNTB is absent in dfw2J mutants. A: cells were defined as medial if located in the medial third of the MNTB or lateral if located in the lateral third of the MNTB. B: there was a significant increase in the size of lateral cells compared with medial cells in the wild-type animals (*P ≤ 0.001). There was no significant increase in the size of lateral cells in +/dfw2J, dfw/dfw, dfw2J/dfw2J, or DTR mice. Error bars show SE. C: individual average cell size for medial and lateral cells in each MNTB. D: scatterplot of location along the tonotopic axis vs. cross-sectional surface area for 1 MNTB from a wild-type and a dfw2J/dfw2J mouse. The linear regression is significantly different from zero for wild type (P = 0.01) but not for dfw2J/dfw2J.
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Figure 3: Medial-to-lateral soma size gradient in the MNTB is absent in dfw2J mutants. A: cells were defined as medial if located in the medial third of the MNTB or lateral if located in the lateral third of the MNTB. B: there was a significant increase in the size of lateral cells compared with medial cells in the wild-type animals (*P ≤ 0.001). There was no significant increase in the size of lateral cells in +/dfw2J, dfw/dfw, dfw2J/dfw2J, or DTR mice. Error bars show SE. C: individual average cell size for medial and lateral cells in each MNTB. D: scatterplot of location along the tonotopic axis vs. cross-sectional surface area for 1 MNTB from a wild-type and a dfw2J/dfw2J mouse. The linear regression is significantly different from zero for wild type (P = 0.01) but not for dfw2J/dfw2J.
Mentions: MNTB neurons were significantly smaller in dfw2J/dfw2J (128.36 ± 7.54 μm2) than in WT (151.89 ± 1.11 μm2; Fig. 2, C and F; F = 5.894; P = 0.04). To determine whether these differences showed any tonotopic relationship, the nucleus was divided into thirds and neurons were assigned to medial, central, and lateral groups (Fig. 3A). We defined PMCA2 function as the percentage of PMCA2 protein, determined by the number of functional alleles possessed by an animal, multiplied by the PMCA2 pumping efficiency, determined by biochemical assay (Penheiter et al. 2001) and compared to WT. We tested a range of PMCA2 function from WT (which have 100% protein), +/dfw2J with ∼50% protein, dfw/dfw with ∼30% function as measured by a calcium clearance assay (Penheiter et al. 2001), and dfw2J/dfw2J, which have no functional PCMA2 protein (Table 1). In WT animals, medial neurons were significantly smaller (136.01 ± 2.66 μm2) than lateral neurons (157.71 ± 5.05 μm2; Fig. 3B; P = 0.02). In +/dfw2J, the location-dependent difference in neuronal cell size was decreased and no longer significant (Fig. 3B; P = 0.08). The size difference was decreased further in dfw/dfw and was absent in the dfw2J/dfw2J mice (Fig. 3B). Although absolute neuronal soma size varied slightly between animals, comparing the size difference in medial and lateral neurons for each individual mouse confirmed the presence or absence of the overall size gradient in the different genotypes (Fig. 3C). Neuronal soma size data of all measured individual neurons from one WT MNTB and one dfw2J/dfw2J MNTB are shown as an example in Fig. 3D. The slope of the linear regression for neuronal soma size is significantly nonzero in WT mice (Fig. 3D; P = 0.01), while no relationship between neuronal soma size and tonotopic location was found in dfw2J/dfw2J, demonstrating that there is a neuronal cell size gradient in WT that is absent in dfw2J/dfw2J.

View Article: PubMed Central - PubMed

ABSTRACT

Neurons of the medial nucleus of the trapezoid body (MNTB) act as fast-spiking inhibitory interneurons within the auditory brain stem. The MNTB is topographically organized, with low sound frequencies encoded laterally and high frequencies medially. We discovered a cell size gradient along this axis: lateral neurons are larger than medial neurons. The absence of this gradient in deaf mice lacking plasma membrane calcium ATPase 2 suggests an activity-dependent, calcium-mediated mechanism that controls neuronal soma size.

No MeSH data available.


Related in: MedlinePlus