GABA Transporter-1 Activity Modulates Hippocampal Theta Oscillation and Theta Burst Stimulation-Induced Long-Term Potentiation
ABSTRACT 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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ABSTRACT: Subchronic treatment with the NMDA antagonist phencyclidine (PCP) produces behavioural abnormalities in rodents which are considered a reliable pharmacological model of neurocognitive deficits in schizophrenia. Alterations in prefrontal neuronal firing after acute PCP administration have been observed, however enduring changes in prefrontal activity after subchronic PCP treatment have not been studied. To address this we have recorded cortical oscillations and unit responses in putative cortical pyramidal cells in subchronic PCP-treated rats (2mg/kg twice daily for 7 days) under urethane anaesthesia. We found that this regimen reduced theta oscillations in medial prefrontal cortex. It further produced abnormal cortical synchronization in putative cortical pyramidal cells. These alterations in prefrontal cortex functioning may contribute to cognitive deficits seen in subchronic NMDA antagonist pre-treated animals in prefrontal-dependent tasks. Copyright © 2014. Published by Elsevier Ltd.Neuroscience 12/2014; 287. DOI:10.1016/j.neuroscience.2014.12.014 · 3.33 Impact Factor
Article: Theta-burst LTP[Show abstract] [Hide abstract]
ABSTRACT: A model for induction of LTP by theta-burst stimulation is presented.•Theta-burst stimulation is shown to be more efficient than tetanic stimulation.•Associative synaptic interactions during theta bursts are limited to major dendritic compartments.•Theta-burst LTP is more sensitive to many experimental conditions than is tetanus-induced LTP.Brain Research 10/2014; DOI:10.1016/j.brainres.2014.10.034 · 2.83 Impact Factor
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ABSTRACT: Seizures were induced by flurothyl inhalation. Rats were intramuscularly treated with progesterone after each seizure. Results demonstrated that glutamate transporter 2 and γ-aminobutyric acid transporter 1 expression levels were significantly increased in the cerebral cortex and hippocampus of the developing rat brain following recurrent seizures. After progesterone treatment, glutamate transporter 2 protein expression was upregulated, but γ-aminobutyric acid transporter 1 levels decreased. These results suggest that glutamate transporter 2 and γ-aminobutyric acid transporter 1 are involved in the pathological processes of epilepsy. Progesterone can help maintain a balance between excitatory and inhibitory systems by modulating the amino acid transporter system, and protect the developing brain after recurrent seizures.Neural Regeneration Research 09/2012; 7(26):2036-42. DOI:10.3969/j.issn.1673-5374.2012.26.005 · 0.23 Impact Factor