Journal Article

FZJ-2018-01232

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Neuroanatomy of pain-deficiency and cross-modal activation in calcium channel subunit (CACN) α2δ3 knockout mice

Landmann, J. (Corresponding author) ; Richter, F. ; Oros-Peusquens, A.-M.FZJ* ; Shah, N. J.FZJ* ; Classen, J. ; Neely, G. G. ; Richter, A. ; Penninger, J. M. ; Bechmann, I.

2018
Springer Berlin

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Please use a persistent id in citations: doi:10.1007/s00429-017-1473-4

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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Contributing Institute(s):

1. Physik der Medizinischen Bildgebung (INM-4)
2. JARA-BRAIN (JARA-BRAIN)

Research Program(s):

1. 573 - Neuroimaging (POF3-573) (POF3-573)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection ; Zoological Record

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