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Publication : NGL-2 regulates input-specific synapse development in CA1 pyramidal neurons.

First Author  DeNardo LA Year  2012
Journal  Neuron Volume  76
Issue  4 Pages  762-75
PubMed ID  23177961 Mgi Jnum  J:323166
Mgi Id  MGI:6843279 Doi  10.1016/j.neuron.2012.10.013
Citation  DeNardo LA, et al. (2012) NGL-2 regulates input-specific synapse development in CA1 pyramidal neurons. Neuron 76(4):762-75
abstractText  An important organizing feature of the CNS is that individual neurons receive input from many different sources. Independent regulation of synaptic input is critical for the function and adaptive responses of the nervous system, but the underlying molecular mechanisms are not well understood. We identify the leucine-rich repeat (LRR)-containing protein NGL-2 (Lrrc4) as a key regulator of input-specific synapse development in the hippocampus. Using genetic deletion and shRNA-mediated knockdown, we demonstrate a role for NGL-2 in regulating the strength of synaptic transmission and spine density specifically at Schaffer collateral synapses in the stratum radiatum (SR) in CA1. NGL-2 protein is restricted to SR and spine regulation requires NGL-2's LRR and PDZ-binding domains. Finally, loss of NGL-2 disrupts cooperative interactions between distal and proximal synapses in CA1 pyramidal cells. These results demonstrate that NGL-2 is critical for pathway-specific synapse development and functional integration of distinct inputs.
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