AUTHOR=Nishiyama Makoto , Togashi Kazunobu , Aihara Takeshi , Hong Kyonsoo 

TITLE=GABAergic activities control spike timing- and frequency-dependent long-term depression at hippocampal excitatory synapses

JOURNAL=Frontiers in Synaptic Neuroscience

VOLUME=2

YEAR=2010

URL=https://www.frontiersin.org/journals/synaptic-neuroscience/articles/10.3389/fnsyn.2010.00022

DOI=10.3389/fnsyn.2010.00022

ISSN=1663-3563

ABSTRACT=<p>GABAergic interneuronal network activities in the hippocampus control a variety of neural functions, including learning and memory, by regulating θ and γ oscillations. How these GABAergic activities at pre- and postsynaptic sites of hippocampal CA1 pyramidal cells differentially contribute to synaptic function and plasticity during their repetitive pre- and postsynaptic spiking at θ and γ oscillations is largely unknown. We show here that activities mediated by postsynaptic GABA<sub>A</sub>Rs and presynaptic GABA<sub>B</sub>Rs determine, respectively, the spike timing- and frequency-dependence of activity-induced synaptic modifications at Schaffer collateral-CA1 excitatory synapses. We demonstrate that both feedforward and feedback GABA<sub>A</sub>R-mediated inhibition in the postsynaptic cell controls the spike timing-dependent long-term depression of excitatory inputs (“<italic>e</italic>-LTD”) at the θ frequency. We also show that feedback postsynaptic inhibition specifically causes <italic>e</italic>-LTD of inputs that induce small postsynaptic currents (&lt;70 pA) with LTP-timing, thus enforcing the requirement of cooperativity for induction of long-term potentiation at excitatory inputs (“<italic>e</italic>-LTP”). Furthermore, under spike-timing protocols that induce <italic>e</italic>-LTP and <italic>e</italic>-LTD at excitatory synapses, we observed parallel induction of LTP and LTD at inhibitory inputs (“<italic>i</italic>-LTP” and “<italic>i</italic>-LTD”) to the same postsynaptic cells. Finally, we show that presynaptic GABA<sub>B</sub>R-mediated inhibition plays a major role in the induction of frequency-dependent <italic>e</italic>-LTD at α and β frequencies. These observations demonstrate the critical influence of GABAergic interneuronal network activities in regulating the spike timing- and frequency-dependences of long-term synaptic modifications in the hippocampus.</p>