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Erschienen in: Brain Structure and Function 1/2018

21.07.2017 | Original Article

Neuroanatomy of pain-deficiency and cross-modal activation in calcium channel subunit (CACN) α2δ3 knockout mice

verfasst von: Julia Landmann, Franziska Richter, Ana-Maria Oros-Peusquens, N. Jon Shah, Joseph Classen, G. Gregory Neely, Angelika Richter, Josef M. Penninger, Ingo Bechmann

Erschienen in: Brain Structure and Function | Ausgabe 1/2018

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Abstract

The phenotype of calcium channel subunit (CACN) α2δ3 knockout (KO) mice includes sensory cross-activation and deficient pain perception. Sensory cross-activation defines the activation of a sensory cortical region by input from another modality due to reorganization in the brain such as after sensory loss. To obtain mechanistic insight into both phenomena, we employed a comprehensive battery of neuroanatomical techniques. While CACNα2δ3 was ubiquitously expressed in wild-type mice, it was absent in α2δ3 KO animals. Immunostaining of α1A, α1B, and α1E revealed upregulation of N-type and R-type, but not P/Q-type Cav2 channels in cortical neurons of CACNα2δ3 KO mice. Compared to wild-type mice, axonal processes in somatosensory cortex were enhanced, and dendritic processes reduced, in CACNα2δ3 KO mice. Immunohistochemical and MRI analyses, investigating morphology, thalamocortical and intra-/intercortical trajectories, revealed a disparity between projection and commissural fibers with reduction of the number of spatial specificity of thalamocortical projections. L1cam staining revealed wide-ranging projections of thalamocortical fibers reaching both somatosensory/motor and visual cortical areas. Activation (c-fos+) of excitatory and inhibitory neurons suggested that deficient pain perception in α2δ3 KO mice is unlikely to result from cortical disinhibition. Collectively, our data demonstrate that knock out of CACN α2δ3 results in some structural abnormalities whose functional implications converge to dedifferentiation of sensory activation.
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Metadaten
Titel
Neuroanatomy of pain-deficiency and cross-modal activation in calcium channel subunit (CACN) α2δ3 knockout mice
verfasst von
Julia Landmann
Franziska Richter
Ana-Maria Oros-Peusquens
N. Jon Shah
Joseph Classen
G. Gregory Neely
Angelika Richter
Josef M. Penninger
Ingo Bechmann
Publikationsdatum
21.07.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Brain Structure and Function / Ausgabe 1/2018
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-017-1473-4

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