Reduced Anxiety and Depression-Like Behaviors in Mice Lacking GABA Transporter Subtype 1

Liu, Guoxiang; Cai, Guo Qiang; Cai, Yuanheng; Sheng, Zhenfeng; Jiang, Jie; Mei, Zhengtong; Wang, Zhu Gang; Guo, Lihe; Fei, Jian

doi:10.1038/sj.npp.1301281

Cited by 118 publications

(97 citation statements)

References 49 publications

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“…S7, available at www.jneurosci. org as supplemental material), consistent with a previous finding that GAT1 KO mice showed reduced anxiety and depressionlike behaviors (Liu et al, 2007). Whether the reduction of theta oscillatory frequency in GAT1 KO mice during novelty exploration is causally related to the hyperlocomotor activity remains to be investigated.…”

Section: Gat1 Deletion Reduced the Frequency Of Hippocampal Theta Oscsupporting

confidence: 88%

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

Gong

Li²,

Cai³

et al. 2009

J. Neurosci.

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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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Section: Gat1 Deletion Reduced the Frequency Of Hippocampal Theta Oscsupporting

confidence: 88%

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

Gong

Li²,

Cai³

et al. 2009

J. Neurosci.

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“…Rothman et al (1993) reported that the average concentration of GABA in human brain tissue was 1 to 2 mM kg (1 . Data from recent studies suggest that plasma and cerebrospinal fluid GABA levels were reduced in depressed and depressed alcohol-abusing humans (Roy et al 1991;Petty 1995), while the anxiety level and depression-like behaviors was significantly reduced in rats, mice and humans by increasing GABA (Sayin et al 1992;Sherif et al 1995;Abdou et al 2006;Liu et al 2007). It is widely known that weaning and mixing stresses have a negative effect on weaned pigs.…”

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confidence: 99%

Effect of γ-aminobutyric acid on growth performance, behavior and plasma hormones in weaned pigs

et al. 2015

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. 2015. Effect of g-aminobutyric acid on growth performance, behavior and plasma hormones in weaned pigs. Can. J. Anim. Sci. 95: 165Á171. The study was conducted the effects of dietary g-aminobutyric acid (GABA, 0 and 30 mg kg(1 ) on average daily intake, growth performance, behavior and plasma hormone levels in weaned pigs. A total of 96 28-d-old healthy weaned male pigs (Duroc )Landrace)Yorkshire) with similar weight were randomly assigned into two groups. Six units were included in each treatment, with eight pigs in each unit. The trial lasted 35 d. Four pigs were exchanged between every two pens in the same treatment on day 28. No difference was observed on average daily feed intake, average daily gain and feed-to-gain ratio between the pigs fed 30 mg kg(1 GABA diets and the pigs fed basal diet, respectively. Longer feed consumption time and lower biting incidences were observed in pigs fed GABA, compared with those fed basal diet, respectively. Plasma growth hormone concentration was significantly increased and the plasma concentrations of adrenocorticotrophic hormone and cortisol were lower in weaned pigs in the GABA supplementation group on day 35. Dietary GABA significantly increased the plasma neuropeptide Y concentration on day 14 and day 35. It is indicated that dietary GABA reduced aggressive behavior and regulated endocrine hormones in weaned pigs, ultimately reducing the negative influences of stress (weaning and mixing) on the pigs.

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“…Thus, the enhanced activity of GABA B receptors we show here with GS-39783, and the decreased levels of phasic inhibition shown previously at MeCP2-deficient synapses (Chao et al, 2010;Jin et al, 2013), can co-exist in systems with decreased GAT-1 transporter activity. It is also noteworthy that many of the behavioral deficits and general phenotypes of GAT-1 knockout mice (Chiu et al, 2005;Liu et al, 2007) display considerable overlap with those of MeCP2-deficient mice (Katz et al, 2012). These include an impaired hind limb clasp reflex, pronounced tremor, decreased ambulatory and rearing activity, impaired balance, and altered anxiety responsiveness.…”

Section: Discussionmentioning

confidence: 99%

A Role for Diminished GABA Transporter Activity in the Cortical Discharge Phenotype of MeCP2-Deficient Mice

Zhang

Wither

Lang

et al. 2015

Neuropsychopharmacol

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Cortical network hyper-excitability is a common phenotype in mouse models lacking the transcriptional regulator methyl-CPG-binding protein 2 (MeCP2). Here, we implicate enhanced GABA B receptor activity stemming from diminished cortical expression of the GABA transporter GAT-1 in the genesis of this network hyper-excitability. We found that administering the activity-dependent GABA B receptor allosteric modulator GS-39783 to female Mecp2 +/ − mice at doses producing no effect in wild-type mice strongly potentiated their basal rates of spontaneous cortical discharge activity. Consistently, administering the GABA B receptor antagonist CGP-35348 significantly decreased basal discharge activity in these mice. Expression analysis revealed that while GABA B or extra-synaptic GABA A receptor prevalence is preserved in the MeCP2-deficient cortex, the expression of GAT-1 is significantly reduced from wild-type levels. This decrease in GAT-1 expression is consequential, as low doses of the GAT-1 inhibitor NO-711 that had no effects in wild-type mice strongly exacerbated cortical discharge activity in female Mecp2 +/ − mice. Taken together, these data indicate that the absence of MeCP2 leads to decreased cortical levels of the GAT-1 GABA transporter, which facilitates cortical network hyper-excitability in MeCP2-deficient mice by increasing the activity of cortical GABA B receptors.

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Reduced Anxiety and Depression-Like Behaviors in Mice Lacking GABA Transporter Subtype 1

Cited by 118 publications

References 49 publications

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

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

Effect of γ-aminobutyric acid on growth performance, behavior and plasma hormones in weaned pigs

A Role for Diminished GABA Transporter Activity in the Cortical Discharge Phenotype of MeCP2-Deficient Mice

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