Assembly and Maintenance of GABAergic Synapses

Understanding the mechanisms underlying Axon Growth and Guidance is key to finding the root cause of neurological diseases and discovering potential therapies.

In this important study, researchers TrkB is required for the localization of an Ig superfamily cell adhesion molecule, Contactin-1, in Golgi and granule cells and the absence of Contactin-1 also results in deficits in inhibitory synaptic development. This demonstrates that TrkB controls the assembly and maintenance of GABAergic synapses and suggest that TrkB functions, in part, through promoting synaptic adhesion: TrkB (Tropomyosin-Related Kinase B) Controls the Assembly and Maintenance of GABAergic Synapses in the Cerebellar Cortex. The Journal of Neuroscience, February 23, 2011 • 31(8):2769 –2780 • 276

Contactin-1 IHC and WB

Images: Inactivation of TrkB kinase activity disrupts the localization of GABAergic synaptic proteins. A–I, Homozygous mice carrying TrkB F616A allele were treated with water or 1NMPP1 from P0 to P28 and analyzed at P28. The localization of GAD65 (green; B), GAD67 (green; E) and gephyrin (red; H ) in the IGL is reduced in TrkB F616A mice treated with 1NMPP1 compared with TrkB F616A mice treated with water (A, D, G). C, F, I, Quantification of the area ratio of GAD65:vGluT1 (C), GAD67:vGluT1 (F ) and gephyrin:vGluT1 expression (I) in control and 1NMPP1-treated mice. J–R, Homozygousmice carrying TrkB F616A allele were treated with water or 1NMPP1 from P30 to P50 and analyzed at P50. The localization of GAD65 (green; K ), GAD67 (green; N ) and gephyrin (red; Q) is reduced in TrkB F616A mice treated with 1NMPP1 compared with control (J, M, P). L, O, R, Quantification of the area ratio of GAD65:vGluT1 (L), GAD67:vGluT1 (O) and gephyrin:vGluT1 expression (R) in control and 1NMPP1-treated mice. Scale bar, 10 um.