Visualization of corticofugal projections during early cortical development in a τ‐GFP‐transgenic mouse

Abstract

The first postmitotic neurons in the developing neocortex establish the preplate layer. These early-born neurons have a significant influence on the circuitry of the developing cortex. However, the exact timing and trajectory of their projections, between cortical hemispheres and intra- and extra-cortical regions, remain unresolved. Here, we describe the creation of a transgenic mouse using a 1.3 kb golli promoter element of the myelin basic protein gene to target expression of a tau-green fluorescent protein (GFP) fusion protein in the cell bodies and processes of pioneer cortical neurons. During embryonic and early neonatal development, the timing and patterning of process extension from these neurons was examined. Analysis of tau-GFP fluorescent fibers revealed that progression of early labeled projections was interrupted unexpectedly by transient pauses at the corticostriatal and telencephalic-diencephalic boundaries before invading the thalamus just prior to birth. After birth the pioneering projections differentially invaded the thalamus, excluding some nuclei, e.g. medial and lateral geniculate, until postnatal days 10-14. Early labeled projections were also found to cross to the contralateral hemisphere as well as to the superior colliculus. These results indicate that early corticothalamic projections appear to pause before invading specific subcortical regions during development, that there is developmental regulation of innervation of individual thalamic nuclei, and that these early-generated neurons also establish early projections to commissural and subcortical targets.

EphB receptor forward signaling regulates area-specific reciprocal thalamic and cortical axon pathfinding

“…Rosa-tdTomato and TetO-tdTomato mice were acquired from Jackson Laboratories (48,49). The Fezf2-GFP and Golli-tau-GFP transgenic mice are previously described (27,28). PCR genotyping was performed using published primer sets.…”

“…S4) (28), and (ii) Golli-tau-GFP mice that express a tau-GFP fusion protein under the control of the Golli gene promoter, which confers selective expression in cortical subplate and layer-6 neurons (CTAs) (Fig. S4) (27). In Fezf2-GFP;EphB1/2 DKO mice at E14.5, we observed clear L1-CAM + TCA guidance defects in the ventral VTel in a region ventral to the GFP + cortical axons (Fig.…”

Early Development of the Thalamic Inhibitory Feedback Loop in the Primary Somatosensory System of the Newborn Mice

“…The first nVPM-to-nRT (Mitrofanis and Baker, 1993) and corticothalamic (Jacobs et al, 2007) axons reach the nRT at birth, but there has been no systematic study of the EPSC changes with growing from P0 to P9. In the S1 cortex, previous work has shown that the relative contribution of the NMDARs at the TC synapses decreases during the first postnatal week (Crair and Malenka, 1995).…”

“…The second input originates in the layer 6 barrel cortex (L6Cx), and sends axon collaterals in the nRT before invading the nVPM (Bourassa et al, 1995;Liu et al, 2001;Ulrich, 2003, 2004). The electrical stimulation of nVPM can activate both the somatodendritic region of the nVPMto-nRT relay neurons and the axonal endings of the corticothalamic fibers that have already invaded the nVPM during the first postnatal week (Jacobs et al, 2007). Recordings were first performed during a restricted period of development (P7-P9) to investigate the possibility to discriminate nVPM-to-nRT and L6Cx-to-nRT EPSCs at Ϫ70 mV.…”

“…Somatic whole-cell recordings were made of the nVPM relay neurons identified by their position in the thalamus, their large soma, and their prominent dendrites. To evoke unitary IPSCs in the nVPM, we used minimal electrical stimulation (see Materials and Methods) of the nRT in the presence of 10 M NBQX and 50 M D-AP-5 to block the disynaptic IPSCs attributable to activation of the TC axons and the monosynaptic EPSCs attributable to activation of the corticothalamic fibers (Golshani et al, 1998;Gentet and Ulrich, 2004;Jacobs et al, 2007). Recordings were first made in P7-P9 mice (Fig.…”