GABA(B) receptor activation mediates frequency-dependent plasticity of developing GABAergic synapses
Chun Xu1, Man-xia Zhao, Mu-ming Poo
1Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road Shanghai 200031, China.
Nature Neuroscience
|October 28, 2008
Summary
Synaptic plasticity in developing rat hippocampus is frequency-dependent. High-frequency stimulation (20-50 Hz) causes potentiation, while low-frequency (5 Hz) causes depression, mediated by GABA(B) receptors.
Area of Science:
- Neuroscience
- Synaptic Plasticity
- GABAergic Signaling
Background:
- Activity-dependent synaptic plasticity is crucial for neural circuit development.
- Glutamatergic synapse modification is known to be frequency-dependent.
- The plasticity mechanisms of developing GABAergic synapses remain less understood.
Purpose of the Study:
- To investigate the frequency-dependence of long-term synaptic modification in developing rat hippocampal GABAergic synapses.
- To elucidate the role of GABA(B) receptors (GABA(B)Rs) in activity-induced GABAergic synaptic plasticity.
- To identify the molecular mechanisms underlying frequency-dependent potentiation and depression.
Main Methods:
- Induction of synaptic plasticity using repetitive coincident pre- and postsynaptic spiking at different frequencies (5 Hz, 20-50 Hz).
- Pharmacological manipulation of GABA(B) receptor activity using antagonists and agonists (baclofen).
- Assessment of postsynaptic mechanisms, including Na(+)/K(+)/2Cl(-) co-transporter activity and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) phosphorylation.
Main Results:
- Repetitive spiking at 20-50 Hz induced long-term potentiation (LTP) of GABAergic synapses.
- Spiking at 5 Hz resulted in long-term depression (LTD).
- LTP was blocked by GABA(B)R antagonists, while LTD was independent of GABA(B)R activation but could be converted to potentiation by enhancing GABA(B)R activity. Potentiation involved increased Na(+)/K(+)/2Cl(-) co-transporter activity and CaMKII phosphorylation at Thr286, which was enhanced by baclofen.
Conclusions:
- Postsynaptic activation of GABA(B) receptors mediates frequency-dependent potentiation of developing GABAergic synapses.
- GABAergic synaptic plasticity exhibits frequency-dependent properties similar to glutamatergic synapses.
- The findings highlight the critical role of GABA(B)Rs and specific molecular players in shaping inhibitory synaptic development and function.
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