Abstract：
:Postsynaptic Density Protein-95 (PSD-95) is a major scaffolding protein in the excitatory synapses in the brain and a critical regulator of synaptic maturation for NMDA and AMPA receptors. PSD-95 deficiency has been linked to cognitive and learning deficits implicated in neurodevelopmental disorders such as autism and schizophrenia. Previous studies have shown that PSD-95 deficiency causes a significant reduction in the excitatory response in the hippocampus. However, little is known about whether PSD-95 deficiency will affect gamma-aminobutyric acid (GABA)ergic inhibitory synapses. Using a PSD-95 transgenic mouse model (PSD-95+/-), we studied how PSD-95 deficiency affects GABAA receptor expression and function in the medial prefrontal cortex (mPFC) during adolescence. Our results showed a significant increase in the GABAA receptor subunit α1. Correspondingly, there are increases in the frequency and amplitude in spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal neurons in the mPFC of PSD-95+/- mice, along with a significant increase in evoked IPSCs, leading to a dramatic shift in the excitatory-to-inhibitory balance in PSD-95 deficient mice. Furthermore, PSD-95 deficiency promotes inhibitory synapse function via upregulation and trafficking of NLGN2 and reduced GSK3β activity through tyr-216 phosphorylation. Our study provides novel insights on the effects of GABAergic transmission in the mPFC due to PSD-95 deficiency and its potential link with cognitive and learning deficits associated with neuropsychiatric disorders.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
McEachern EP,Coley AA,Yang SS,Gao WJdoi
10.1016/j.neuropharm.2020.108277subject
Has Abstractpub_date
2020-11-15 00:00:00pages
108277eissn
0028-3908issn
1873-7064pii
S0028-3908(20)30345-2journal_volume
179pub_type
杂志文章abstract：:A unique type of limbic seizures, maximal dentate activation, was used to examine the effects of cholinergic and adrenergic agents on the processes involved in epileptogenesis. The time to onset of maximal dentate activation was used to monitor the initiation of seizures while the duration of maximal dentate activatio...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(91)90043-b
更新日期：1991-01-01 00:00:00
abstract：:Rivastigmine, a cholinesterase inhibitor, is successfully used for the symptomatic therapy of Alzheimer's disease (AD) in the clinic. The drug has a very low potential for drug-drug interactions, as has been demonstrated within large clinical trials. Memantine, recently approved by the FDA for the treatment of moderat...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2004.04.009
更新日期：2004-09-01 00:00:00
abstract：:Neural progenitor cells (NPCs) are found in the subventricular zone (SVZ) of the adult brain, a specialized neurogenic niche that might provide a substrate for brain repair after injury. The incomplete knowledge of how NPCs in the niche respond to local signals limits the use of cultured NPCs in the development of cel...
journal_title：Neuropharmacology
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doi：10.1016/j.neuropharm.2008.05.021
更新日期：2008-09-01 00:00:00
abstract：:Rats exhibited a marked suppression of motor activity when placed in the same chamber where they had been given electric shocks. Administration of apomorphine-HCl (0.1, 0.5 and 1.0 mg/kg, i.p.) attenuated the conditioned suppression, dose-dependently, but did not facilitate motor activity of control (i.e. non-shocked)...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90125-9
更新日期：1983-07-01 00:00:00
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journal_title：Neuropharmacology
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doi：10.1016/0028-3908(89)90076-2
更新日期：1989-05-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(02)00043-6
更新日期：2002-06-01 00:00:00
abstract：:Flavopiridol was developed as a drug for cancer therapy due to its ability to inhibit cell cycle progression by targeting cyclin-dependent kinases (CDKs). In this study, we show that flavopiridol may also have a neuroprotective action. We show that at therapeutic dosage (or at micromolar range), flavopiridol almost co...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(03)00204-1
更新日期：2003-10-01 00:00:00
abstract：:The excitatory amino acid antagonist, D-alpha-aminoadipate, was found to be a potent antagonist of responses to N-methyl-D-aspartate and L-aspartate, but less potent against L-glutamate responses of neurones in the rat caudal trigeminal nucleus. The responses to quisqualate and kainate were relatively unaffected by D-...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(82)90020-x
更新日期：1982-05-01 00:00:00
abstract：:Sodium phenobarbitone was tested for its ability to antagonise the anxiogenic effects of compounds acting at three different central sites. These compounds were: FG 7142, a beta-carboline which acts at the benzodiazepine binding site on the GABA-benzodiazepine receptor complex; pentylenetetrazole, which acts at the pi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(89)90072-5
更新日期：1989-01-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.06.014
更新日期：2018-08-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2004.06.003
更新日期：2004-09-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2005.08.015
更新日期：2005-11-01 00:00:00
abstract：:The effects of a stimulation of dopamine D1 receptors by using (+/-)SKF 38393 on the cortical EEG in rats which were chronically implanted with electrodes were studied. Administration of SKF 38393 (3 or 9 mg/kg, s.c.) produced alterations suggesting an arousal in the EEG: the power in all of the frequency bands decrea...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(93)90175-3
更新日期：1993-05-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.02.016
更新日期：2008-06-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90157-0
更新日期：1983-05-01 00:00:00
abstract：:Opioids are thought to increase the excitability of hippocampal pyramidal cells by decreasing release of neurotransmitter from inhibitory interneurons. This study compared the actions of the opioid agonist normorphine, and the GABA receptor antagonist bicuculline, on the responses of CA1 pyramidal cells to afferent st...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(89)90152-4
更新日期：1989-07-01 00:00:00
abstract：:G protein regulated inward rectifying potassium channels (GIRKs) are activated by G protein coupled receptors (GPCRs) via the G protein betagamma subunits. However, little is known about the effects of different GPCRs on the deactivation kinetics of transmitter-mediated GIRK currents. In the present study we investiga...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00080-0
更新日期：2000-09-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00195-7
更新日期：2001-06-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.03.007
更新日期：2014-07-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(97)00163-9
更新日期：1997-11-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(91)90203-n
更新日期：1991-02-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.10.013
更新日期：2008-02-01 00:00:00
abstract：:The patterns of spontaneous firing recorded from 25 cells in slice preparations of rat cerebral cortex were characterised using inter-spike interval plots (ISI). Histograms of the ISI showed two peaks having modal values of 20 and 82ms, corresponding to episodes of high frequency bursts of action potentials, and a low...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(85)90062-0
更新日期：1985-06-01 00:00:00
abstract：:Muscarinic acetylcholine receptors (mAChRs) are G proteincoupled receptors (GPCRs) that mediate the metabotropic actions of acetylcholine (ACh). There are five subtypes of mAChR, M1 - M5, which are expressed throughout the central nervous system (CNS) on numerous cell types and represent promising treatment targets fo...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2017.11.018
更新日期：2018-07-01 00:00:00
abstract：:High-frequency stimulation of afferents to the supraoptic nucleus (SON) results in a robust increase in the frequency and amplitude of pharmacologically isolated, tetrodotoxin-resistant, miniature excitatory postsynaptic currents (mEPSCs) lasting for 5-20 min. This increase in mEPSC frequency, termed short-term potent...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(01)00098-3
更新日期：2001-10-01 00:00:00
abstract：:Depolarizations provoked by acetylcholine (ACh) and three dicholines, succinylcholine (SCh), glutarylcholine (GCh) and azelainylcholine (AzCh) were measured in normal and 3-7 days denervated muscles of adult, and in normal muscles of 0-27 days old mice and rats. Soleus and flexor digitorum superficialis muscles were m...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(89)90032-4
更新日期：1989-04-01 00:00:00
abstract：:Hippocampal Long-Term Potentiation (LTP) is facilitated by BDNF, through the activation of tropomyosin-related kinase B (TrkB) receptors. However, an influence of BDNF upon Long-Term Depression (LTD) was also shown. The present work aimed to further evaluate the effect of BDNF and TrkB receptors upon CA1 hippocampal L...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.12.010
更新日期：2014-04-01 00:00:00
abstract：:The serotonin transporter (SERT) facilitates high affinity reuptake of 5-HT from the extracellular fluid and dysregulation of transporter function has been implicated in a range of mood disorders including depression. Recent studies have linked immune system activation to depression as well as to altered serotonin tra...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.04.023
更新日期：2018-07-15 00:00:00
abstract：:Alcohol produces many subjective and objective effects in man including pleasure, sedation, anxiolysis, plus impaired eye movements and memory. In human volunteers we have used a newly available GABA-A/benzodiazepine receptor inverse agonist that is selective for the alpha5 subtype (a5IA) to evaluate the role of this ...
journal_title：Neuropharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/j.neuropharm.2007.08.008
更新日期：2007-12-01 00:00:00
abstract：:Vortioxetine is a multimodal drug that blocks serotonin (5-HT) reuptake and directly modulates 5-HT receptors. The effects of subacute and long-term administration of vortioxetine on various aspects of catecholamine and glutamate systems were investigated using single-unit extracellular recordings and microiontophores...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.10.036
更新日期：2018-01-01 00:00:00
