Abstract：
:Long-term potentiation (LTP) resembles memory in that it is initially unstable and then, over about 30 min, becomes increasingly resistant to disruption. Here we present an hypothesis to account for this initial consolidation effect and consider implications that follow from it. Anatomical studies indicate that LTP is accompanied by changes in spine morphology and therefore likely involves cytoskeletal changes. Accordingly, theta bursts initiate calpain-mediated proteolysis of the actin cross-linking protein spectrin and trigger actin polymerization in spine heads, two effects indicative of cytoskeletal reorganization. Polymerization occurs within 2 min, has the same threshold as LTP, is dependent on integrins, and becomes resistant to disruption over 30 min. We propose that the stabilization of the new cytoskeletal organization, and thus of a new spine morphology, underlies the initial phase of LTP consolidation. This hypothesis helps explain the diverse array of proteins and signaling cascades implicated in LTP, as well as the often-contradictory results about contributions of particular molecules. It also provides a novel explanation for why LTP is potently modulated by factors likely to be released during theta trains (e.g., BDNF). Finally, building on evidence that normal patterns of activity reverse LTP, we suggest that consolidation provides a delay that allows brain networks to sculpt newly formed memories.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Lynch G,Rex CS,Gall CMdoi
10.1016/j.neuropharm.2006.07.027subject
Has Abstractpub_date
2007-01-01 00:00:00pages
12-23issue
1eissn
0028-3908issn
1873-7064pii
S0028-3908(06)00237-1journal_volume
52pub_type
杂志文章,评审abstract：:Acamprosate is clinically used to treat alcohol-dependent patients. While the molecular and pharmacological mechanisms of acamprosate remain unclear, it has been shown to regulate γ-aminobutyric acid (GABA) or glutamate levels in the cortex and striatum. To investigate the effect of acamprosate on brain metabolites in...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.02.022
更新日期：2012-06-01 00:00:00
abstract：:Granule cell axon terminals of rat cerebellum possess benzodiazepine-insensitive GABA(A) receptors mediating glutamate release. We have investigated the ability of benzodiazepines, ethanol and furosemide to modulate the function of these receptors in the cerebellum of alcohol-tolerant (AT) and alcohol-nontolerant (ANT...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(99)00025-8
更新日期：1999-09-01 00:00:00
abstract：:gamma-Aminobutyric acid type A (GABA(A)) receptors are an important target for general anesthetics in the central nervous system. Site-directed mutagenesis techniques have identified amino acid residues that are important for the positive modulation of GABA(A) receptors by general anesthetics. In the present study, we...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(01)00141-1
更新日期：2001-12-01 00:00:00
abstract：:Opioid drugs such as heroin interact directly with opioid receptors whilst other addictive drugs, including marijuana, alcohol and nicotine indirectly activate endogenous opioid systems to contribute to their rewarding properties. The opioid system therefore plays a key role in addiction neurobiology and continues to ...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2008.07.033
更新日期：2009-01-01 00:00:00
abstract：:The monosynaptic reflex (MSR), recorded in vitro from the neonatal rat spinal cord, was depressed by 5-hydroxytryptamine (5-HT) and 5-HT receptor agonists. The results, together with our previous findings, indicate an apparent rank order of potency: 5-carboxamidotryptamine (5-CT) > sumatriptan > methysergide > 5-HT > ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(94)90188-0
更新日期：1994-07-01 00:00:00
abstract：:Bilateral injection of gamma-aminobutyric acid (GABA, 10-300 micrograms) into the substantia nigra (pars reticulata) of rats produced stereotyped sniffing and had an analgesic-like effect on the hot-plate but not on the tail-flick test. These effects of GABA (30 micrograms) were suppressed by simultaneous administrati...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(88)90097-4
更新日期：1988-08-01 00:00:00
abstract：:Selegiline is an irreversible inhibitor of monoamine oxidase B with trophic and neuroprotective effects. Because of evidence for decreased dopaminergic function during the withdrawal syndromes associated with opiates and other medications with potential for abuse, we investigated effects of treatment with selegiline o...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00093-8
更新日期：1998-08-01 00:00:00
abstract：:The modulatory effects exerted by the glucocorticoid hydrocortisone (HC) on the nicotinic acetylcholine receptor (AChR) were studied in mutants of the alpha subunit M4 transmembrane region. Based on the photoaffinity labeling of alpha M4 412 with the steroid promegestone this position was mutated to different residues...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(02)00068-0
更新日期：2002-07-01 00:00:00
abstract：:The selective benzodiazepine antagonist RO 15-1788, labelled with carbon 11 [11C] RO 15-1788, as a specific marker, together with positron emission tomography, allows the in vivo study of benzodiazepine receptors in primates. In addition, when coupled with recordings of electroencephalographic activity, this method of...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(87)90171-7
更新日期：1987-10-01 00:00:00
abstract：:Efforts to translate sub-anesthetic ketamine infusions into widespread clinical use have centered around developing medications with comparable neurobiological activity, but with attenuated psychoactive effects so as to minimize the risk of behavioral toxicity and abuse liability. Converging lines of research, however...
journal_title：Neuropharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.neuropharm.2018.01.005
更新日期：2018-11-01 00:00:00
abstract：:Grip strength deficit is a measure of pain-induced functional disability in rheumatic disease. We tested whether this parameter and tactile allodynia, the standard pain measure in preclinical studies, show parallels in their response to analgesics and basic mechanisms. Mice with periarticular injections of complete Fr...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.07.029
更新日期：2017-10-01 00:00:00
abstract：:Tau hyperphosphorylation and memory deficit are characteristic alterations of Alzheimer's disease (AD), and glycogen synthase kinase-3 (GSK-3) plays a crucial role in these AD-like changes. We have reported that activation of GSK-3 through ventricular injection of wortmannin and GF-109203X (WT/GFX, 100 microM each) in...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.02.008
更新日期：2007-06-01 00:00:00
abstract：:A study has been undertaken to identify the category of receptors mediating the inhibitory effects of adenosine on evoked activity in slices of olfactory cortex in the rat. The approach has been to measure the relative potencies of adenosine and a range of structural analogues [2-chloroadenosine, 2' deoxyadenosine, cy...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(85)90195-9
更新日期：1985-11-01 00:00:00
abstract：:3,4-Methlylenedioxymethamphetamine (MDMA) administration (4 x 15 mg/kg) on a single day has been shown to cause path integration deficits in rats. While most animal experiments focus on single binge-type models of MDMA use, many MDMA users take the drug on a recurring basis. The purpose of this study was to compare th...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.07.006
更新日期：2008-12-01 00:00:00
abstract：:In the present studies, an attempt was made to elucidate the role of endogenous opioid inputs to the depressor region of the caudal ventrolateral medulla in the tonic regulation of arterial pressure and to examine the subtype(s) of receptor underlying any observed effects by use of receptor-specific antagonists. The d...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(91)90064-i
更新日期：1991-04-01 00:00:00
abstract：:Inflammation plays a central role in the processes associated with neurodegeneration. The inflammatory response is mediated by activated microglia that release inflammatory mediators to the neuronal environment. Microglia-derived lysosomal cathepsins, including cathepsin X, are increasingly recognized as important med...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.11.019
更新日期：2017-03-01 00:00:00
abstract：:Long-term consumption of ethanol affects cortical areas that are important for learning and memory, cognition, and decision-making. Deficits in cortical function may contribute to alcohol-abuse disorders by impeding an individual's ability to control drinking. Previous studies from this laboratory show that acute etha...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.03.031
更新日期：2016-08-01 00:00:00
abstract：:The basic unsolved questions concerning GABAA receptors are: "How many receptor subtypes exist?", "What subtypes are used by which types of neuron and where are they located on the cell?", and "What are the functions of the different subtypes?" As described in this Review, the cerebellum is an ideal vertebrate brain r...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0028-3908(96)00076-7
更新日期：1996-01-01 00:00:00
abstract：:Glibenclamide (GBC), a sulfonylurea receptor 1 blocker, emerges recently as a promising neuron protectant in various neurological disorders. This study aimed to determine whether GBC improves survival and neurological outcome of status epilepticus (SE). Male Sprague-Dawley rats successfully undergoing SE for 2.5 h (n ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.04.016
更新日期：2017-07-15 00:00:00
abstract：:Potentiation of the 5-HT3 receptor-mediated ion current in mouse N1E-115 neuroblastoma cells by 5-hydroxyindole (5-OHi) and three analogues (5-aminoindole, catechol and indole) was examined using whole-cell voltage clamp and single channel patch clamp techniques. The substances tested enhanced the amplitude of the max...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(97)00045-2
更新日期：1997-04-01 00:00:00
abstract：:Alterations in rapid eye movement sleep (REM) have been suggested as valid translational efficacy markers: activation of the metabotropic glutamate receptor 2 (mGluR2) was shown to increase REM latency and to decrease REM duration. The present paper addresses the effects on vigilance states of the mGluR2 positive allo...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.11.031
更新日期：2016-04-01 00:00:00
abstract：:GABAA and glycine receptors are close relatives in the "gene superfamily" of ligand-gated ion channels, but have distinctly different pharmacology. For example, barbiturates have two effects on GABAA receptors (GABAA-R): at low micromolar concentrations (2-5 microM), the anesthetic barbiturate methohexital potentiates...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(96)00088-3
更新日期：1996-01-01 00:00:00
abstract：:The bed nucleus of the stria terminalis (BNST) is a forebrain structure implicated in physiological and behavioral responses to emotional stress. However, the local neurochemical mechanisms mediating the BNST control of stress responses are not fully known. Here, we investigated the involvement of BNST cholinergic neu...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.10.018
更新日期：2016-02-01 00:00:00
abstract：:Addiction is associated with changes in synaptic plasticity mediated, in part, by alterations in the trafficking and stabilization of AMPA receptors at synapses within the nucleus accumbens. Exposure to cocaine can lead to protein kinase C-mediated phosphorylation of GluA2 AMPA subunits and this phosphorylation event ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.09.010
更新日期：2016-12-01 00:00:00
abstract：:Lesions of the ventral hippocampus (VH) in neonatal rats result in post-pubertal alterations in a number of cognitive, social and motor behaviors that bear some analogy to schizophrenia. Increased sensitivity to stress and psychostimulants and prefrontal functional changes in the lesioned animals suggest an involvemen...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2003.08.001
更新日期：2004-01-01 00:00:00
abstract：:The majority of the fibroblast growth factor receptor 1-serotonin 1 A receptor (FGFR1-5-HT1AR) heterocomplexes in the hippocampus appeared to be located mainly in the neuronal networks and a relevant target for antidepressant drugs. Through a neurochemical and electrophysiological analysis it was therefore tested in t...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108070
更新日期：2020-06-15 00:00:00
abstract：:Chronic pain states are highly prevalent and yet poorly controlled by currently available analgesics, representing an enormous clinical, societal, and economic burden. Existing pain medications have significant limitations and adverse effects including tolerance, dependence, gastrointestinal dysfunction, cognitive imp...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2017.06.015
更新日期：2017-09-15 00:00:00
abstract：:Calcium currents in the inferior colliculus (IC) are thought to play an important role in ethanol withdrawal hyperexcitability. Here, we report on the modulation of Ca(2+) channel currents in acutely dissociated IC neurons of rats, exhibiting higher incidence of audiogenic seizures when subjected to ethanol withdrawal...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(03)00191-6
更新日期：2003-09-01 00:00:00
abstract：:Biogenic monoamines are involved in the regulation of various processes in both neural and non-neural cells during development. The present study aimed to identify the regulatory effects of serotonin (5-HT) and its precursors (l-tryptophan and 5-hydroxytryptophan, 5-HTP) on proliferation and cell death in mouse embryo...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2019.107862
更新日期：2019-11-25 00:00:00
abstract：:The effect of an acute intraperitoneal (i.p.) injection of acetaldehyde, 20 mg/kg or 100 mg/kg, on the microdialysate content of both amino acids and monoamines was studies in the nucleus accumbens (NA) by a microdialysis technique. Acetaldehyde, ACH, which was detectable at levels of 50-130 mumol/g brain tissue 10 mi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(97)00007-5
更新日期：1997-02-01 00:00:00
