Abstract:
:We have used a focal stimulation method to study neurotransmission at synapses onto hippocampal pyramidal neurons in cultures derived from neonatal rats. Single functional boutons were visualized by activity-dependent preloading with the fluorescent dye FM1-43, then focally stimulated by localized application of elevated K+/Ca2+ solution via a puffer pipette, while postsynaptic currents were recorded under whole cell voltage clamp (Liu and Tsien, 1995). This paper gives a detailed description of the main properties of this experimental system and of information it has provided about fundamental properties of hippocampal synapses. Most of the experiments focused on excitatory postsynaptic currents (EPSCs), but preliminary recordings of inhibitory events (IPSCs) are also reported here. The unitary EPSCs at individual synapses varied greatly in amplitude, but were relatively uniform in their time course. The frequency of the synaptic events was greatly reduced by lowering the external Ca2+ concentration or by application of baclofen, a GABAB receptor agonist. Frequent repetitive stimulation produced a decline in the incidence of EPSCs that was readily reversed upon rest. We attribute the decline to exhaustion of a pool of available vesicles; typically, recovery proceeded with a time constant of approximately 40 sec (23 degrees C), and involved a vesicular pool capable of generating approximately 90 EPSCs without recycling. While synaptic currents were broadly distributed in amplitude (Bekkers et al., 1990), this distribution was remarkably similar at multiple synapses on a given postsynaptic neuron. The median synaptic current amplitude varied 4-fold across different cells, decreasing markedly with increasingly dense synaptic innervation. The implications of these results for cellular signal processing and quantal analysis are discussed.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Liu G,Tsien RWdoi
10.1016/0028-3908(95)00143-tsubject
Has Abstractpub_date
1995-11-01 00:00:00pages
1407-21issue
11eissn
0028-3908issn
1873-7064pii
002839089500143Tjournal_volume
34pub_type
杂志文章abstract::Nicotinic receptors containing the alpha7 gene product are among the most abundant in the nervous system. Because of their widespread distribution and high relative permeability to calcium, the receptors regulate a diverse array of cellular events. On chick ciliary neurons the receptors are concentrated on somatic spi...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(00)00132-5
更新日期:2000-10-01 00:00:00
abstract::The central serotonin2B receptor (5-HT2BR) is currently considered as an interesting pharmacological target for improved treatment of drug addiction. In the present study, we assessed the effect of two selective 5-HT2BR antagonists, RS 127445 and LY 266097, on cocaine-induced hyperlocomotion and dopamine (DA) outflow ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2015.06.012
更新日期:2015-10-01 00:00:00
abstract::The effects of 5-hydroxytryptamine (5-HT) on neuronal excitability, evaluated as depolarization-induced firing rate, and on amino acid release, measured as electrically-evoked [(3)H]GABA and [(3)H]d-aspartate efflux, were investigated in rat primary cortical neuronal cultures. 5-HT displayed a concentration-dependent,...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.10.017
更新日期:2007-03-01 00:00:00
abstract::Metabotropic glutamate receptor subtype 5 (mGluR5), encoded by the GRM5 gene, represents a compelling novel drug target for the treatment of schizophrenia. mGluR5 is a postsynaptic G-protein coupled glutamate receptor strongly linked with several critical cellular processes that are reported to be disrupted in schizop...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2015.08.003
更新日期:2017-03-15 00:00:00
abstract::There is strong evidence that blocking CB1 receptors may reduce alcohol intake in alcohol-dependent individuals. However, there is still limited evidence that CB1 receptor antagonists may also be beneficial in the attenuation of alcohol withdrawal syndrome, even though alcohol withdrawal appears to be milder in CB1 re...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2008.02.005
更新日期:2008-05-01 00:00:00
abstract::This paper evaluates the involvement of hippocampal ATP-sensitive potassium channels (K(ATP)) in learning and memory. After confirming expression of the Kir6.2 subunit in the CA3 region of C57BL/6J mice, we performed intra-hippocampal pharmacological injections of specific openers and blockers of K(ATP) channels. The ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2008.11.001
更新日期:2009-03-01 00:00:00
abstract::Benzodiazepines (BZDs) and barbiturates exert their CNS actions by binding to GABA-A receptors (GABARs). The structural mechanisms by which these drugs allosterically modulate GABAR function, to either enhance or inhibit GABA-gated current, are poorly understood. Here, we used the substituted cysteine accessibility me...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2010.11.009
更新日期:2011-02-01 00:00:00
abstract::Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide produced in the lateral hypothalamus and zona incerta that increases food intake. The neuronal pathways and behavioral mechanisms mediating the orexigenic effects of MCH are poorly understood, as is the extent to which MCH-mediated feeding outcomes are ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2020.108270
更新日期:2020-11-01 00:00:00
abstract::The N-methyl-D-aspartate (NMDA) antagonist ifenprodil and several structurally related compounds are highly selective for the NR2B-containing receptor subtype. This selectivity could provide an explanation for the reported difference of the analgesic and side-effect profile of ifenprodil-like compounds from other NMDA...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(00)00148-9
更新日期:2001-01-01 00:00:00
abstract::The hippocampal slice is a popular model system in which to study the cellular properties of long-term potentiation (LTP). Synaptogenesis induced by exposure to ice-cold artificial cerebrospinal fluid (ACSF), however, raises the concern that morphological correlates of LTP might be obscured, especially in mature slice...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.06.020
更新日期:2007-01-01 00:00:00
abstract::Benzodiazepine drugs (BZ) are used for anxiety, insomnia, and seizures. They worsen memory, especially in large doses, but the mechanism of this action is uncertain. In micromolar concentrations, benzodiazepines have been shown to reduce long-term potentiation (LTP), which could be a cellular basis for their amnesic a...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(95)00182-4
更新日期:1996-03-01 00:00:00
abstract::Diazepam binding inhibitor (DBI) is a neuromodulatory peptide for gamma-aminobutyric acid (GABA) neurotransmission. Levels of DBI in cerebrospinal fluid (CSF) were found to be elevated in depressed patients, when compared to age- and sex-matched normal controls. Levels of the peptide, corticotropin-releasing hormone (...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(11)80014-6
更新日期:1991-12-01 00:00:00
abstract::The accumulation of β-amyloid (Aβ) is one of the hallmarks of Alzheimer disease (AD). Beyond the inflammatory reactions promoted by Aβ, it has been demonstrated that the prokineticin (PK) system, composed of the chemokine prokineticin 2 (PK2) and its receptors, is involved in Aβ toxicity. In this study we have analyze...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.12.012
更新日期:2017-04-01 00:00:00
abstract::Dopamine (DA) is a major catecholamine neurotransmitter in the mammalian brain that controls neural circuits involved in the cognitive, emotional, and motor aspects of goal-directed behavior. Accordingly, perturbations in DA neurotransmission play a central role in several neuropsychiatric disorders. Somewhat surprisi...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2017.04.033
更新日期:2017-09-15 00:00:00
abstract::Ethanol addiction is a serious public health problem that still needs more effective pharmacological treatment. A key factor in the development and maintenance of this disease is the advent of neuroadaptations in the mesocorticolimbic brain pathway upon chronic ethanol abuse. In general, these neuroadaptations are mal...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.07.009
更新日期:2016-11-01 00:00:00
abstract::In previous studies, we have shown that agonists influence the ability of D2 dopamine receptors to couple to G proteins and here we extend this work. The human D2Short dopamine receptor and a natural polymorphism of this D(2Short)(Ser311Cys), have been studied by co-expressing the receptors in insect cells with Gbeta1...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2004.06.010
更新日期:2004-11-01 00:00:00
abstract::Methylazoxymethanol (MAM)-treated pregnant rat at gestation day (GD) 17 has been shown to be a valuable developmental animal model for schizophrenia. Yet, this model remains to be established in mice. In the present study, we examined behavioral, cytoarchitectural, and neurochemical changes in the offspring of MAM-tre...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2019.02.034
更新日期:2019-05-15 00:00:00
abstract::Treatment-related sexual dysfunction is a common side effect of antidepressants and contributes to patient non-compliance or treatment cessation. However, the multimodal antidepressant, vortioxetine, demonstrates low sexual side effects in depressed patients. To investigate the mechanisms involved, sexual behavior was...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2017.04.017
更新日期:2017-07-15 00:00:00
abstract::Attention-deficit hyperactivity disorder (ADHD) is a clinically and genetically heterogeneous syndrome which is comorbid with childhood conduct disorder, alcoholism, substance abuse, dis-social personality disorder, and affective disorders. A small but consistent overlap with autistic symptoms has also been establishe...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2009.08.011
更新日期:2009-12-01 00:00:00
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...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2020.108277
更新日期:2020-11-15 00:00:00
abstract::Neurotensin (NTS) is a neuropeptide neurotransmitter expressed in the central and peripheral nervous systems. Many studies over the years have revealed a number of roles for this neuropeptide in body temperature regulation, feeding, analgesia, ethanol sensitivity, psychosis, substance use, and pain. This review provid...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2020.108005
更新日期:2020-05-01 00:00:00
abstract::Nicotinic acetylcholine receptors (nAChRs) are highly conserved between humans and non-human primates. Conservation exists at the level of genomic structure, protein structure and epigenetics. Overall homology of nAChRs at the protein level is 98% in macaques versus 89% in mice, which is highly relevant for evaluating...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2015.01.023
更新日期:2015-09-01 00:00:00
abstract::The aim of this study was to investigate the pharmacological characteristics of the 5-hydroxytryptamine-(5-HT)-induced electrical response in cultured neuroblastoma N1E-115 cells of the mouse. In these cells 5-HT induces a transient membrane depolarization, which is associated with a transient inward current, that has...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(88)90048-2
更新日期:1988-03-01 00:00:00
abstract::The effect of (U-54494A) cis-3,4-dichloro-N-methyl-N-[2-(1-Pyrrolidinyl)- cyclohexyl] benzamide monohydrochloride, an excitatory amino acid antagonist, on N-methyl-D-aspartic acid (NMDA)- and K(+)-evoked release of [3H]acetylcholine [( 3H]ACh) from slices of striatum was investigated. For the purpose of comparison, MK...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(92)90019-l
更新日期:1992-02-01 00:00:00
abstract::The nomenclature system used to characterize 5-hydroxytryptamine receptor subtypes remains controversial. To date, the majority of nomenclature systems have been on the differential pharmacological properties of the receptors. However, the availability of molecular biological data allows for a nomenclature system base...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(92)90138-f
更新日期:1992-07-01 00:00:00
abstract:RATIONALE:Diabetes mellitus (DM) is a major risk factor for Alzheimer's disease and vascular dementia. Few animal models exist that focus on the metabolic contributions to dementia onset and progression. Thus, there is strong scientific rationale to explore the effects of streptozotocin (STZ), a diabetogenic compound, ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2018.04.021
更新日期:2018-07-15 00:00:00
abstract::The present review gives an overview of current pharmacological treatment options of tic disorders and Tourette Syndrome (TS). After a short summary on phenomenology, clinical course and comorbid conditions we review indications for pharmacological treatment in detail. Unfortunately, standardized and large enough drug...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2012.05.043
更新日期:2013-05-01 00:00:00
abstract::Administration of 0.13% lead acetate solution as drinking fluid to breeding mice was without significant effect on the numbers of live or dead births or on weight of pups at 1 day. The appearance of fur was delayed and the body weights at 21 days and 31-38 weeks were smaller than in controls. On weaning, the treated o...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(86)90036-5
更新日期:1986-02-01 00:00:00
abstract::Serotonin (5-HT) neurons are involved in wake promotion and exert a strong inhibitory influence on rapid eye movement (REM) sleep. Such effects have been ascribed, at least in part to the action of 5-HT at post-synaptic 5-HT1A receptors (5-HT1AR) in the brainstem, a major wake/REM sleep regulatory center. However, the...
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
abstract::Although there is evidence from in vitro studies to suggest that NO synthesis may be involved in the induction of hippocampal LTP, other in vitro studies and experiments conducted in vivo have provided conflicting results. In agreement with previous work conducted in this laboratory using an i.p. route of administrati...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(94)90040-x
更新日期:1994-11-01 00:00:00