| First Author | Landmann J | Year | 2018 |
| Journal | Brain Struct Funct | Volume | 223 |
| Issue | 1 | Pages | 111-130 |
| PubMed ID | 28733833 | Mgi Jnum | J:306011 |
| Mgi Id | MGI:6708449 | Doi | 10.1007/s00429-017-1473-4 |
| Citation | Landmann J, et al. (2018) Neuroanatomy of pain-deficiency and cross-modal activation in calcium channel subunit (CACN) alpha2delta3 knockout mice. Brain Struct Funct 223(1):111-130 |
| abstractText | The phenotype of calcium channel subunit (CACN) alpha2delta3 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 CACNalpha2delta3 was ubiquitously expressed in wild-type mice, it was absent in alpha2delta3 KO animals. Immunostaining of alpha1A, alpha1B, and alpha1E revealed upregulation of N-type and R-type, but not P/Q-type Cav2 channels in cortical neurons of CACNalpha2delta3 KO mice. Compared to wild-type mice, axonal processes in somatosensory cortex were enhanced, and dendritic processes reduced, in CACNalpha2delta3 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 alpha2delta3 KO mice is unlikely to result from cortical disinhibition. Collectively, our data demonstrate that knock out of CACN alpha2delta3 results in some structural abnormalities whose functional implications converge to dedifferentiation of sensory activation. |
