Role of α4-containing GABAA receptors in limiting synaptic plasticity and spatial learning of female mice during the pubertal period

@article{Shen2017RoleO,
  title={Role of $\alpha$4-containing GABAA receptors in limiting synaptic plasticity and spatial learning of female mice during the pubertal period},
  author={Hui Shen and N. Sabaliauskas and Lie Yang and C. Aoki and S. Smith},
  journal={Brain Research},
  year={2017},
  volume={1654},
  pages={116-122}
}
Expression of α4βδ GABAA receptors (GABARs) increases at the onset of puberty on dendritic spines of CA1 hippocampal pyramidal cells. These receptors reduce activation of NMDA receptors (NMDARs), impair induction of long-term potentiation (LTP) and reduce hippocampal-dependent spatial learning. These effects are not seen in the δ-/- mouse, implicating α4βδ GABARs. Here we show that knock-out of α4 also restores synaptic plasticity and spatial learning in female mice at the onset of puberty… Expand
Increased Dendritic Branching of and Reduced δ-GABAA Receptor Expression on Parvalbumin-Positive Interneurons Increase Inhibitory Currents and Reduce Synaptic Plasticity at Puberty in Female Mouse CA1 Hippocampus
TLDR
It is suggested that phasic inhibition generated by PV+ interneurons is increased at puberty when it contributes to impairments in synaptic plasticity, which may have relevance for the changes in cognitive function reported during early adolescence. Expand
Pubertal hormones increase hippocampal expression of α4βδ GABAA receptors
TLDR
It is suggested that both the rise in circulating levels of E2 and the decline in hippocampal THP levels at the onset of puberty trigger maximal levels of α4βδ expression in the CA1 hippocampus. Expand
Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spines
TLDR
It is shown that α4βδ GABARs trigger adolescent pruning, an extrasynaptic inhibitory receptor which first emerges on dendritic spines at puberty in female mice, and that in their absence, pruning is prevented and cognition is not optimal. Expand
α4-GABAA receptors of hippocampal pyramidal neurons are associated with resilience against activity-based anorexia for adolescent female mice but not for males
TLDR
Knowing of sex‐related differences in the underlying mechanisms of resilience to ABA indicates that drugs targeting &agr;4&bgr;&dgr;‐GABAARs may be helpful for treating stress‐induced anxiety and anorexia nervosa of females but not males. Expand
Transcriptomics of Gabra4 knockout mice reveals common NMDAR pathways underlying autism, memory, and epilepsy
TLDR
An upregulation of the NMDAR system at the center of the converged pathways underlying high-functioning autism-like and anti-epilepsy phenotypes is revealed. Expand
International Union of Basic and Clinical Pharmacology. CVI: GABAA Receptor Subtype- and Function-selective Ligands: Key Issues in Translation to Humans
TLDR
An up-to-date review on the currently available GABAA receptor subtype-selective ligands and proposals for the future development of ligands with better anxioselectivity in humans are made. Expand
Hippocampal amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid GluA1 (AMPA GluA1) receptor subunit involves in learning and memory improvement following treatment with Centella asiatica extract in adolescent rats
TLDR
The aim of this study was to investigate the effects of a C. asiatica extract on the enhancement of learning and memory in adolescent rats. Expand
Hippocampal Neurotransmitter Inhibition Suppressed During Gaming Explained by Skill Rather Than Gamer Status
TLDR
While there were no significant differences in hippocampal GABA before and after gaming for gamers and non-gamers alike, there was a significant quadratic regression between performance on a spatial working memory task and post-gaming hippocampusal GABA concentrations. Expand
Animal Models of Eating Disorders
Binge eating is an extreme form of loss of control over the consumption of food. The foods consumed in a binge are typically highly processed (HP) foods with unnaturally high levels of refinedExpand
...
1
2
...

References

SHOWING 1-10 OF 92 REFERENCES
α5GABAA Receptor Activity Sets the Threshold for Long-Term Potentiation and Constrains Hippocampus-Dependent Memory
TLDR
The results showed that α5GABAAR activity raises the threshold for induction of long-term potentiation in a highly specific band of stimulation frequencies (10–20 Hz) through mechanisms that are predominantly independent of inhibitory synaptic transmission. Expand
A Critical Role for α4βδ GABAA Receptors in Shaping Learning Deficits at Puberty in Mice
TLDR
The emergence of α4βδ GABARs at puberty impairs learning, an effect that can be reversed by a stress steroid, and the stress steroid THP, which reduces tonic inhibition at puberty, facilitated learning. Expand
Enhanced Learning and Memory and Altered GABAergic Synaptic Transmission in Mice Lacking the α5 Subunit of the GABAAReceptor
TLDR
Data suggest that α5-containing GABAA receptors play a key role in cognitive processes by controlling a component of synaptic transmission in the CA1 region of the hippocampus. Expand
Acutely increasing δGABAA receptor activity impairs memory and inhibits synaptic plasticity in the hippocampus
TLDR
The results showed that THIP impaired performance in the Morris water maze, contextual fear conditioning and object recognition tasks in WT mice but not Gabrd−/− mice, an effect that was blocked by GABAA receptor antagonist bicuculline. Expand
Neurosteroid effects at α4βδ GABAA receptors alter spatial learning and synaptic plasticity in CA1 hippocampus across the estrous cycle of the mouse
TLDR
It is shown that impairments in both CA1 hippocampal LTP and spatial learning observed on the morning of proestrus are due to increased dendritic expression of α4βδ GABAA receptors (GABARs) on CA1 pyramidal cells, as assessed by electron microscopic techniques, compared with estrus and diestrus. Expand
Knockout of the γ-aminobutyric acid receptor subunit α4 reduces functional δ-containing extrasynaptic receptors in hippocampal pyramidal cells at the onset of puberty
TLDR
It is demonstrated that α4 subunit expression strongly influences the pubertal increase of δ subunits at the plasma membrane, and that genetic deletion of α4 serves as a functional knock-down of ε-containing GABARs. Expand
Excitability Changes Related to GABAA Receptor Plasticity during Pregnancy
TLDR
The findings indicate that alterations in δGABAAR expression during pregnancy result in brain region-specific increases in neuronal excitability that are restored by the high levels of allopregnanolone under normal conditions but under pathological conditions may result in neurological and psychiatric disorders associated with pregnancy and postpartum. Expand
Reversal of neurosteroid effects at α4β2δ GABAA receptors triggers anxiety at puberty
Puberty is characterized by mood swings and anxiety, which are often produced by stress. Here we show that THP (allopregnanolone), a steroid that is released as a result of stress, increases anxietyExpand
Trace and contextual fear conditioning is enhanced in mice lacking the α4 subunit of the GABAA receptor
TLDR
The convergent findings between alpha4 and delta knockout mice suggests that tonic inhibition mediated by alpha4betadelta GABA(A) receptors negatively modulates learning and memory processes and provides further evidence that Tonic inhibition makes important functional contributions to learning and behavior. Expand
Trace fear conditioning is enhanced in mice lacking the delta subunit of the GABAA receptor.
TLDR
It is proposed that activation of GABA(A)Rs by neuroactive steroids inhibits learning processes in the hippocampus, and Knockouts are immune to this effect because of the reduced neurosteroid sensitivity that accompanies deletion of the delta subunit. Expand
...
1
2
3
4
5
...