GABA Transporter-1 Activity Modulates Hippocampal Theta Oscillation and Theta Burst Stimulation-Induced Long-Term Potentiation

Institute of Neuroscience and State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 12/2009; 29(50):15836-45. DOI: 10.1523/JNEUROSCI.4643-09.2009
Source: PubMed


The network oscillation and synaptic plasticity are known to be regulated by GABAergic inhibition, but how they are affected by changes in the GABA transporter activity remains unclear. Here we show that in the CA1 region of mouse hippocampus, pharmacological blockade or genetic deletion of GABA transporter-1 (GAT1) specifically impaired long-term potentiation (LTP) induced by theta burst stimulation, but had no effect on LTP induced by high-frequency stimulation or long-term depression induced by low-frequency stimulation. The extent of LTP impairment depended on the precise burst frequency, with significant impairment at 3-7 Hz that correlated with the time course of elevated GABAergic inhibition caused by GAT1 disruption. Furthermore, in vivo electrophysiological recordings showed that GAT1 gene deletion reduced the frequency of hippocampal theta oscillation. Moreover, behavioral studies showed that GAT1 knock-out mice also exhibited impaired hippocampus-dependent learning and memory. Together, these results have highlighted the important link between GABAergic inhibition and hippocampal theta oscillation, both of which are critical for synaptic plasticity and learning behaviors.

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    • "GABAergic neurons are the principal inhibitory neurons and one of the major local circuit neurons (Moore, 1993) which has been implicated in the regulation of a variety of behavioral functions such as learning and memory (Chapouthier, 1989; Vinogradova et al., 1998). In fact, GABAergic influence is the key to generate rhythmic synchronization of neurons during theta and gamma activity in different brain regions, contributing to neuronal communication and memory processing (Somogyi and Klausberger, 2005; Gong et al., 2009). Cortical and hippocampal function depends on optimum levels of inhibition (Borhegyi et al., 2004; Kaifosh et al., 2013; Xu et al., 2013; Bissonette et al., 2014) to "
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    • "On the other hand, the frequency at which theta power reached maximum in the GAT1 KO mice was significantly left-shifted from 7.5 Hz to 6.0 Hz, although this peak frequency remained in theta band. This result is consistent with the previously reported by Gong et al. [32]. Thus, GAT1 activity does not affect the physiological expression of theta oscillation activity, but modulates the precise frequency of this oscillation. "
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    • "We found that GAT1 KO mice showed significantly higher locomotor activity than WT in a single 30-min exposure to the open field (WT, 52.3±2.0 m; KO, 70.7±5.3 m; n = 8–9 for each genotype, p<0.01, t-test, Fig. 1A1), consistent with our previous finding [10]. Furthermore, all genotype mice showed similar short-term habituation within the 30-min test represented by the distance traveled per 5 min (genotype×time interaction, F(5, 84) = 0.498, p>0.1, ANOVA, Fig. 1A2) and similar long-term habituation within four consecutive daily tests (genotype×day interaction, F(3, 60) = 0.021, p>0.1, ANOVA, Fig. 1A3), while GAT1 KO mice showed persistent locomotor hyperactivity in both tests (short-term, F(1, 84) = 26.459, p<0.001, "
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