Figure 4.

Role of ionotropic GABA receptors on radial migration. (A) Model of GABA_A and GABA_A-rho receptor dependent radial migration in the neonatal cerebral cortex, which shows outside directed GABA gradient (gray colored gradient). In the IZ migrating neurons express functional GABA_A receptors (blue discs) and GABA_A-rho receptors (orange discs), whereas in the CP migrating neurons express only functional GABA_A receptors. Due to the outside directed GABA gradient the low-affinity GABA_A receptors are only activated in the CP, while the lower GABA concentration in the IZ is sufficient to activate the high affinity GABA_A-rho receptors. Activation of GABA_A-rho receptors is necessary to support migration in the IZ (GO sign), while activation of GABA_A receptors contributes to termination of migration (STOP sign). (B) Blockade of GABA_A receptors with gabazine facilitates radial migration. Figures illustrate red fluorescent protein (RFP)-positive cells in control (left) and gabazine-treated (right) GAD67^GFP/GFP fetuses at E17.5, which were injected with gabazine at E14.5 immediately after the electroporation of the RFP vectors. (C) Digital photographs of Nissl-stained coronal sections from a P7 rat that received at P0 on the cortical surface an Elvax implant containing DMSO (top, control), the GABA_A antagonist bicuculline methiodide (middle, BMI) or the GABA_A agonist muscimol (bottom). Note upper layer heterotopia due to increased radial migration in BMI- and muscimol-treated animals. Scale bar in B, C middle and C bottom corresponds to 200 µm, in C top to 500 µm. Modified with permission from Denter et al. (2010) (A), Furukawa et al. (2014) (B), and Heck et al. (2007) (C).