The Somatosensory Cortex ofreelerMutant Mice Shows Absent Layering But Intact Formation and Behavioral Activation of Columnar Somatotopic Maps

Abstract

Sensory information acquired via the large facial whiskers is processed and relayed in the whisker-to-barrel pathway, which shows multiple somatotopic maps of the receptor periphery. These maps consist of individual structural modules, the development of which may require intact cortical lamination. In the present study we examined the whisker-to-barrel pathway in the reeler mouse and thus used a model with disturbed cortical organization. A combination of histological (fluorescent Nissl and cytochrome oxidase staining) as well as molecular methods (c-Fos and laminar markers Rgs8, RORB, and ER81 expression) revealed wild type-equivalent modules in reeler. At the neocortical level, however, we found extensive alterations in the layout of the individual modules of the map. Nevertheless, they showed a columnar organization that included compartments equivalent to those of their wild-type counterparts. Moreover, all examined modules showed distinct activation as a consequence of behavioral whisker stimulation. Analysis of the magnitude of the cortical lamination defect surprisingly revealed an extensive disorganization, rather than an inversion, as assumed previously. Striking developmental plasticity of thalamic innervation, as suggested by vGluT2 immunohistochemistry, seems to ensure the proper formation of columnar modules and topological maps even under highly disorganized conditions.

Mapping remodeling of thalamocortical projections in the living reeler mouse brain by diffusion tractography

“…5 D and J), probably due to the highly disorganized cortical lamination induced by the reelin gene mutation. This finding is very much in contrast to earlier studies but in good agreement with recent molecular and functional imaging (32,33). We therefore focused our investigation on in vivo comparison of the wild-type and reeler TCP to get a better understanding of the dynamic interplay between cortical patterning and thalamic axon guidance.…”

“…Involved in the guidance of neuronal migration during development, reelin has a tremendous implication in the organization of laminated structures (31). In rodents, reelin mutation results in the reeler phenotype (30,32), characterized by a major laminar disorganization in the cerebral and cerebellar cortical areas, as well as the hippocampus. Reelin mutations in humans have been described and cause lissencephaly with severe mental retardation (41).…”

“…Our origin-to-termination TCP mapping clearly demonstrated that changes in patterning of the cortical sheet in reeler mutants lead to parallel alterations in the pattern of thalamocortical connectivity. Thalamic fibers from VB are developing alternate routes but finally reach the target neurons spread out across the entire thickness of S1BF (32). This finding suggests the existence of highly specific cell-autonomous target selection mechanisms that control synapse formation in this strongly topographic pathway, and is not compatible with a singular concept based on gradients of attractive and repulsive molecules (7,53).…”

“…In the absence of the reelin protein, a key regulator for neuronal migration and cortical development, newborn neurons fail to reach their normal position in the cortical layers (31). The mutation strongly affects the lamination of S1BF (32), giving rise to an anomaly of cortical cytoarchitecture, which should be incompatible with the development of a normal TCP. Therefore, using our validated tools, we directly investigate the hypothesis of brain structural plasticity by massive remodeling of TC axonal trees in the living reeler brain.…”

Exploring Memory Representations with Activity-Based Genetics

“…Although the precise nature of activity required to induce IEG expression is not clear, the expression of IEGs has been used extensively as a measure of neural activation in response to environmental stimulation and has given results that often track with activity determined by other techniques, such as electrophysiological recording or with known anatomical function and connectivity. For example, cfos is activated in a tonotopic pattern in the auditory brainstem with auditory stimulation (Saint Marie et al 1999) and in a somatotopic pattern in somatosentory cortex following wisker stimulation (Wagener et al 2010). In learning and memory paradigms, such as fear conditioning, there is cfos activation in an array of areas, such as hippocampus, amygdala, prefrontal cortex, and anterior cingulate cortex, that are known to be active and functionally necessary for the learning or retrieval of contextual fear memories (Milanovic et al 1998;Radulovic et al 1998;Bontempi et al 1999;Frankland et al 2004;Knapska and Maren 2009).…”