Functional Thalamocortical Synapse Reorganization from Subplate to Layer IV during Postnatal Development in theReeler-Like Mutant Rat (Shaking Rat Kawasaki)

Abstract

Transient synapse formation between thalamic axons and subplate neurons is thought to be important in thalamocortical targeting.Shaking rat Kawasaki (SRK), having reversed cortical layering similarly observed in reeler mouse, provides an interesting model system to test this idea. The spatial and temporal pattern of excitation was investigated using optical recording with voltage-sensitive dyes in thalamocortical slice preparations from SRK. At postnatal day 0 (P0), a strong optical response was elicited within the superplate of the SRK in the cell layer corresponding to subplate in wild-type (WT) rats. By P3, this response rapidly descended into deep cortical layers comprised of layer IV cells, as identified with 5-bromo-2Ј-deoxyuridine birthdating at embryonic day 17. During the first 3 postnatal days, both the subplate and cortical plate responses were present, but by P7, the subplate response was abolished. Tracing individual axons in SRK revealed that at P0 -P3, a large number of thalamocortical axons reach the superplate, and by P7-P10, the ascending axons develop side branches into the lower or middle cortical layers. Synaptic currents were also demonstrated in WT subplate cells and in SRK superficial cortical cells using whole-cell recording. These currents were elicited monosynaptically, because partial AMPA current blockade did not modify the latencies. These results suggest that the general developmental pattern of synapse formation between thalamic axons and subplate (superplate) neurons in WT and SRK is very similar, and individual thalamic arbors in cortex are considerably remodeled during early postnatal development to find layer IV equivalent neurons.

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

“…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). These results further support our notion that the reeler cortex is not simply inverted, and question findings of a concomitantly inverted thalamocortical projection (33,54). Moreover, probabilistic mapping of the TC projections in subcortical and cortical areas and the MiR axonal tracing revealed a striking feature of the reeler cortex: the formation of a unique columnar-like termination pattern of the TCP.…”

Structural Basis for Map Formation in the Thalamocortical Pathway of the Barrelless Mouse

“…It was further shown that TCA can correct an altered development both during their subcortical trajectory (Higashi et al, 2005) as well as their subsequent growth within cortex (for review, see Rash and Grove, 2006). Although our observations are made in adulthood, it seems that the BRL mutation has neither influenced the subcortical trajectory, nor the termination of TCAs in the appropriate cortical layers.…”

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

“…This seems to ensure the building of the basic cortical module, i.e., the column (Mountcastle, 1997;Douglas and Martin, 2007;Petersen, 2007). Part of this developmental plasticity could be mediated by the proper interaction of early thalamic axons with subplate neurons (Higashi et al, 2005).…”

“…Although several lines of evidence since then have suggested at least a substantial additional smearing of inverted layer borders caused by wrongly positioned cells, the concept of inversion is still frequently used to interpret findings in reeler (D'Arcangelo, 2005;Higashi et al, 2005;Strazielle et al, 2006).…”