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Neural cell adhesion molecule, NCAM, regulates thalamocortical axon pathfinding and the organization of the cortical somatosensory representation in mouse.

Enriquez-Barreto L, Palazzetti C, Brennaman LH, Maness PF, Fairén A - Front Mol Neurosci (2012)

Bottom Line: During the early postnatal period, rostrolateral TC axons within the internal capsule along the ventral telencephalon adopted distorted trajectories in the ventral telencephalon and failed to reach the neocortex in NCAM mutant animals.NCAM mutants showed abnormal segregation of layer IV barrels in a restricted portion of the somatosensory cortex.These results indicate a novel role for NCAM in axonal pathfinding and topographic sorting of TC axons, which may be important for the function of specific territories of sensory representation in the somatosensory cortex.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández San Juan de Alicante, Spain.

ABSTRACT
To study the potential role of neural cell adhesion molecule (NCAM) in the development of thalamocortical (TC) axon topography, wild type, and NCAM mutant mice were analyzed for NCAM expression, projection, and targeting of TC afferents within the somatosensory area of the neocortex. Here we report that NCAM and its α-2,8-linked polysialic acid (PSA) are expressed in developing TC axons during projection to the neocortex. Pathfinding of TC axons in wild type and mutant mice was mapped using anterograde DiI labeling. At embryonic day E16.5, mutant mice displayed misguided TC axons in the dorsal telencephalon, but not in the ventral telencephalon, an intermediate target that initially sorts TC axons toward correct neocortical areas. During the early postnatal period, rostrolateral TC axons within the internal capsule along the ventral telencephalon adopted distorted trajectories in the ventral telencephalon and failed to reach the neocortex in NCAM mutant animals. NCAM mutants showed abnormal segregation of layer IV barrels in a restricted portion of the somatosensory cortex. As shown by Nissl and cytochrome oxidase staining, barrels of the anterolateral barrel subfield (ALBSF) and the most distal barrels of the posteromedial barrel subfield (PMBSF) did not segregate properly in mutant mice. These results indicate a novel role for NCAM in axonal pathfinding and topographic sorting of TC axons, which may be important for the function of specific territories of sensory representation in the somatosensory cortex.

No MeSH data available.


Related in: MedlinePlus

Serotonin immunohistochemistry in the early postnatal somatosensory cortex. (A,B). Serotonin immunostaining highlighted the distribution of TC axons in the developing cortex. At P2, at a time barrel units are not yet formed, immunostaining revealed a uniform distribution of axons in both wild type and mutant mice. (C,D). At P6, serotonin immunoreactivity clustered in layer IV in a manner reminiscent of barrels (highlighted in the inset) in wild type animals (C). In P6 NCAM  mutant mice, TC axons also localized to layer IV but showed a continuous distribution (D). Confocal optical sections. IV, cortical layer IV. Bar: 100 μm.
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Figure 7: Serotonin immunohistochemistry in the early postnatal somatosensory cortex. (A,B). Serotonin immunostaining highlighted the distribution of TC axons in the developing cortex. At P2, at a time barrel units are not yet formed, immunostaining revealed a uniform distribution of axons in both wild type and mutant mice. (C,D). At P6, serotonin immunoreactivity clustered in layer IV in a manner reminiscent of barrels (highlighted in the inset) in wild type animals (C). In P6 NCAM mutant mice, TC axons also localized to layer IV but showed a continuous distribution (D). Confocal optical sections. IV, cortical layer IV. Bar: 100 μm.

Mentions: We first analyzed in early postnatal mice the distribution of TC axons within layer IV of the somatosensory cortex (Figure 7). During the first postnatal week, thalamic fibers navigate through layers V and VI and invade layer IV, which is incompletely differentiated. TC axons assume their characteristic periphery-related pattern and impose a barrel arrangement onto layer IV (Agmon et al., 1993; López-Bendito and Molnár, 2003). Developing TC axons ascend to layer IV where they form spatially periodic clusters of terminations of gradually increasing complexity that correspond to the barrels, rather than branching profusely within lower cortical layers with subsequent retraction (Agmon et al., 1993, 1995). To see how TC axons segregate in NCAM mice, we analyzed the pattern of distribution of thalamic terminals by means of serotonin (5-HT) immunohistochemistry. Thalamic relay neurons transiently express the plasma 5-HT transporter (5-HTT) and the vesicular monoamine transporter type 2 (VMAT2), allowing 5-HT to concentrate in the TC axons and axon terminals during early postnatal life (Lebrand et al., 1996). 5-HT immunostaining was continuous in the forming layer IV of P2 mice, but at P6 it suggested a discrete pattern in wild type mice, but not NCAM mice (Figure 7).


Neural cell adhesion molecule, NCAM, regulates thalamocortical axon pathfinding and the organization of the cortical somatosensory representation in mouse.

Enriquez-Barreto L, Palazzetti C, Brennaman LH, Maness PF, Fairén A - Front Mol Neurosci (2012)

Serotonin immunohistochemistry in the early postnatal somatosensory cortex. (A,B). Serotonin immunostaining highlighted the distribution of TC axons in the developing cortex. At P2, at a time barrel units are not yet formed, immunostaining revealed a uniform distribution of axons in both wild type and mutant mice. (C,D). At P6, serotonin immunoreactivity clustered in layer IV in a manner reminiscent of barrels (highlighted in the inset) in wild type animals (C). In P6 NCAM  mutant mice, TC axons also localized to layer IV but showed a continuous distribution (D). Confocal optical sections. IV, cortical layer IV. Bar: 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3378950&req=5

Figure 7: Serotonin immunohistochemistry in the early postnatal somatosensory cortex. (A,B). Serotonin immunostaining highlighted the distribution of TC axons in the developing cortex. At P2, at a time barrel units are not yet formed, immunostaining revealed a uniform distribution of axons in both wild type and mutant mice. (C,D). At P6, serotonin immunoreactivity clustered in layer IV in a manner reminiscent of barrels (highlighted in the inset) in wild type animals (C). In P6 NCAM mutant mice, TC axons also localized to layer IV but showed a continuous distribution (D). Confocal optical sections. IV, cortical layer IV. Bar: 100 μm.
Mentions: We first analyzed in early postnatal mice the distribution of TC axons within layer IV of the somatosensory cortex (Figure 7). During the first postnatal week, thalamic fibers navigate through layers V and VI and invade layer IV, which is incompletely differentiated. TC axons assume their characteristic periphery-related pattern and impose a barrel arrangement onto layer IV (Agmon et al., 1993; López-Bendito and Molnár, 2003). Developing TC axons ascend to layer IV where they form spatially periodic clusters of terminations of gradually increasing complexity that correspond to the barrels, rather than branching profusely within lower cortical layers with subsequent retraction (Agmon et al., 1993, 1995). To see how TC axons segregate in NCAM mice, we analyzed the pattern of distribution of thalamic terminals by means of serotonin (5-HT) immunohistochemistry. Thalamic relay neurons transiently express the plasma 5-HT transporter (5-HTT) and the vesicular monoamine transporter type 2 (VMAT2), allowing 5-HT to concentrate in the TC axons and axon terminals during early postnatal life (Lebrand et al., 1996). 5-HT immunostaining was continuous in the forming layer IV of P2 mice, but at P6 it suggested a discrete pattern in wild type mice, but not NCAM mice (Figure 7).

Bottom Line: During the early postnatal period, rostrolateral TC axons within the internal capsule along the ventral telencephalon adopted distorted trajectories in the ventral telencephalon and failed to reach the neocortex in NCAM mutant animals.NCAM mutants showed abnormal segregation of layer IV barrels in a restricted portion of the somatosensory cortex.These results indicate a novel role for NCAM in axonal pathfinding and topographic sorting of TC axons, which may be important for the function of specific territories of sensory representation in the somatosensory cortex.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández San Juan de Alicante, Spain.

ABSTRACT
To study the potential role of neural cell adhesion molecule (NCAM) in the development of thalamocortical (TC) axon topography, wild type, and NCAM mutant mice were analyzed for NCAM expression, projection, and targeting of TC afferents within the somatosensory area of the neocortex. Here we report that NCAM and its α-2,8-linked polysialic acid (PSA) are expressed in developing TC axons during projection to the neocortex. Pathfinding of TC axons in wild type and mutant mice was mapped using anterograde DiI labeling. At embryonic day E16.5, mutant mice displayed misguided TC axons in the dorsal telencephalon, but not in the ventral telencephalon, an intermediate target that initially sorts TC axons toward correct neocortical areas. During the early postnatal period, rostrolateral TC axons within the internal capsule along the ventral telencephalon adopted distorted trajectories in the ventral telencephalon and failed to reach the neocortex in NCAM mutant animals. NCAM mutants showed abnormal segregation of layer IV barrels in a restricted portion of the somatosensory cortex. As shown by Nissl and cytochrome oxidase staining, barrels of the anterolateral barrel subfield (ALBSF) and the most distal barrels of the posteromedial barrel subfield (PMBSF) did not segregate properly in mutant mice. These results indicate a novel role for NCAM in axonal pathfinding and topographic sorting of TC axons, which may be important for the function of specific territories of sensory representation in the somatosensory cortex.

No MeSH data available.


Related in: MedlinePlus