GABAB Receptor signaling Modulates Frequency-dependent Plasticity of Developing GABAergic Synapses

Time:2008-10-29

 

On Oct 26, 2008, Nature Neuroscience published online a full original article from ION entitled "GABAB receptor activation mediates frequency-dependent plasticity of developing GABAergic synapses". This work was carried out by graduate students Chun Xu and Man-xia Zhao, under the supervision of Drs. Mu-ming Poo and Xiao-hui Zhang. Activity-induced synaptic modification provides a cellular basis for developmental refinement of neuronal connections and for information storage associated with learning and memory. However, GABAergic synapses have only come into the limelight recently, and plasticity of GABAergic synapses remains largely unexplored, especially in developing animals. In this study, the authors have demonstrated a critical role of GABAB receptors (GABABRs) in frequency-dependent synaptic plasticity of developing hippocampal GABAergic synapses, during early postnatal development when they are still excitatory. They further reveal the cellular mechanism underlying the frequency-dependent long-term potentiation (LTP) induced by coincident pre- and postsynaptic neuronal spikingThree coincident events, postsynaptic spiking, GABAAR activation and GABABR activation are required, which, in turn, result in up-regulation of postsynaptic CaMKII activity and local activity of a Cl- co-transporter NKCC1, leading to the strengthened GABAergic transmission (Figure).  These findings reveal a novel function of GABABRs in the postsynaptic regulation of long-term plasticity of developing GABAergic synapses, and such frequency-dependent plasticity also provides a mechanism for self-refinement of local GABAergic circuits during neural development.

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