Результаты поиска

Kappa opioid receptors regulate hippocampal synaptic homeostasis and epileptogenesis.

OBJECTIVE: Homeostatic synaptic plasticity (HSP) serves as a gain control mechanism at central nervous system (CNS) synapses, including those between the dentate gyrus (DG) and CA3. Improper circuit control of DG-CA3 synapses is hypothesized to underlie epileptogenesis. Here, we sought to (1) identify compounds that preferentially modulate DG-CA3 synapses in primary neuronal culture and (2) determine if these compounds would delay or prevent epileptogenesis in vivo. METHODS: We previously developed and validated an in vitro assay to visualize the behavior of DG-CA3 synapses and predict functi

Astrocyte signaling controls spike timing-dependent depression at neocortical synapses.

Endocannabinoid mediated spike timing-dependent depression (t-LTD) is crucially involved in the development of the sensory neocortex. t-LTD at excitatory synapses in the developing rat barrel cortex requires cannabinoid CB(1) receptor (CB(1)R) activation, as well as activation of NMDA receptors located on the presynaptic terminal, but the exact signaling cascade leading to t-LTD remains unclear. We found that astrocytes are critically involved in t-LTD. Astrocytes gradually increased their Ca(2+) signaling specifically during the induction of t-LTD in a CB(1)R-dependent manner. In this way, as

What a nostril knows: olfactory nerve-evoked AMPA responses increase while NMDA responses decrease at 24-h post-training for lateralized odor preference memory in neonate rat.

Increased AMPA signaling is proposed to mediate long-term memory. Rat neonates acquire odor preferences in a single olfactory bulb if one nostril is occluded at training. Memory testing here confirmed that only trained bulbs support increased odor preference at 24 h. Olfactory nerve field potentials were tested at 24 h in slices from trained and untrained bulbs. A larger AMPA component and a smaller NMDA component characterized responses in the bulb receiving odor preference training. Field potential changes were not seen in a bulbar region separate from the lateral odor-encoding area. These r

Local Ca2+ detection and modulation of synaptic release by astrocytes.

Astrocytes communicate with synapses by means of intracellular calcium ([Ca(2+)](i)) elevations, but local calcium dynamics in astrocytic processes have never been thoroughly investigated. By taking advantage of high-resolution two-photon microscopy, we identify the characteristics of local astrocyte calcium activity in the adult mouse hippocampus. Astrocytic processes showed intense activity, triggered by physiological transmission at neighboring synapses. They encoded synchronous synaptic events generated by sparse action potentials into robust regional (∼12 μm) [Ca(2+)](i) elevations. Unexp

Rapid WAVE dynamics in dendritic spines of cultured hippocampal neurons is mediated by actin polymerization.

The Wiskott-Aldrich syndrome protein family Verprolin-homologous protein (WAVE) complex has been proposed to link Rho GTPase activity with actin polymerization but its role in neuronal plasticity has never been documented. We now examined the presence, distribution and dynamics of WAVE3 in cultured hippocampal neurons. WAVE3 was localized to dendritic spines via its N-terminal domain. Green fluorescent protein (GFP)-tagged WAVE3 clusters demonstrate an F-actin-dependent high rate of local motility. Constitutive Rac activation translocates WAVE3 (via the N-terminus), to the leading edge of lame

Functional organization of rat olfactory bulb glomeruli revealed by optical imaging.

The functional organization and synaptic physiology of olfactory bulb glomeruli were studied in rat in vitro slice preparations stained with the voltage-sensitive dye RH-155. Optical signals were recorded with a 100-element photodiode array at high temporal resolution. Pharmacological and ionic manipulations were used to investigate synaptic responses to stimulation of the olfactory nerve layer (ONL). ONL stimulation evoked a sodium-mediated compound action potential that propagated across the ONL and invaded individual glomeruli. This presynaptic volley evoked calcium-dependent synaptic respo

Synaptic inhibition in the isolated respiratory network of neonatal rats.

Gramicidin-perforated patch-clamp recording revealed phasic Cl(-)-mediated hyperpolarizations in respiratory neurons of the brainstem-spinal cord preparation from newborn rats. The in vitro respiratory rhythm persisted after block of gamma-aminobutyric acid (GABA), i.e. GABAA, receptor-mediated inhibitory postsynaptic potentials (IPSPs) with bicuculline and/or glycinergic IPSPs with strychnine. In one class of expiratory neurons, bicuculline unmasked inspiration-related excitatory postsynaptic potentials (EPSPs), leading to spike discharge. Bicuculline also blocked hyperpolarizations and respi

Activation of kappa-opioid receptors depresses electrically evoked excitatory postsynaptic potentials on 5-HT-sensitive neurones in the rat dorsal raphé nucleus in vitro.

Intracellular recordings from dorsal raphé neurones in slices from rat brains were used to study the actions of kappa-opioid receptor agonists on an excitatory postsynaptic potential (epsp) evoked by local electrical stimulation of afferent terminals. The epsp was observed on all 5-HT-sensitive neurones and was blocked by 1 microM TTX. The epsp was reduced in a dose-dependent manner by the specific kappa-opioid receptor agonist [5R-(5 alpha,7 alpha,8 beta)]-N-methyl-N-[7-(1-pyrrolidinyl)-1- oxaspiro[4.5]dec-8-yl]-4-benzofuranacetamide monohydrochloride (CI-977) (1-100 nM). The effects of CI-97

Analgesic Alkaloids Derived From Traditional Chinese Medicine in Pain Management.

Chronic pain is one of the most prevalent health problems. The establishment of chronic pain is complex. Current medication for chronic pain mainly dependent on anticonvulsants, tricyclic antidepressants and opioidergic drugs. However, they have limited therapeutic efficacy, and some even with severe side effects. We turned our interest into alkaloids separated from traditional Chinese medicine (TCM), that usually act on multiple drug targets. In this article, we introduced the best-studied analgesic alkaloids derived from TCM, including tetrahydropalmatine, aloperine, oxysophocarpine, matrine

Совпадение в полном тексте источника
… (TTXs) and tetrodotoxin-resistant (TTXr) sodium channel in DRG neurons in PNS ( Yu et al., 2019 ) | Inhibiting the release of PGE2 in the inflammatory tissue in CNS and PNS ( Yin et al., 2003 ); Reducting the content of 5-HT in CFA-induced arthritis rat’s blood plasma, while increasing the content of … and tetrodotoxin-resistant sodium channels in DRG neurons (Model: chronic constriction injury model; Dosage: 30 mg/kg; Positive control: gabapentin) ( Yu et al., 2019 ). …

Emerging advances in drug delivery systems (DDSs) for optimizing cancer complications.

The management and treatment of tumor complications pose continuous challenges due to the inherent complexity. However, the advent of drug delivery systems (DDSs) brings promising opportunities to address the tumor complications using innovative technological approaches. This review focuses on common oncological complications, including cancer thrombosis, malignant serous effusion, tumor-associated infections, cancer pain, and treatment-related complications. Emphasis was placed on the application and potential of DDSs in mitigating and treating these tumor complications, and we delved into th

Light-evoked lateral GABAergic inhibition at single bipolar cell synaptic terminals is driven by distinct retinal microcircuits.

Inhibitory amacrine cells (ACs) filter visual signals crossing the retina by modulating the excitatory, glutamatergic output of bipolar cells (BCs) on multiple temporal and spatial scales. Reciprocal feedback from ACs provides focal inhibition that is temporally locked to the activity of presynaptic BC activity, whereas lateral feedback originates from ACs excited by distant BCs. These distinct feedback mechanisms permit temporal and spatial computation at BC terminals. Here, we used a unique preparation to study light-evoked IPSCs recorded from axotomized terminals of ON-type mixed rod/cone B

Pregnenolone sulfate enhances spontaneous glutamate release by inducing presynaptic Ca2+-induced Ca2+ release.

Pregnenolone sulfate (PS) acts as an excitatory neuromodulator and has a variety of neuropharmacological actions, such as memory enhancement and convulsant effects. In the present study, we investigated the effect of PS on glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) in acutely isolated dentate gyrus (DG) hilar neurons by use of a conventional whole-cell patch-clamp technique. PS significantly increased sEPSC frequency in a concentration-dependent manner without affecting the current amplitude, suggesting that PS acts presynaptically to increase the probability of sponta

Strong calcium entry activates mitochondrial superoxide generation, upregulating kinase signaling in hippocampal neurons.

Large increases in cytosolic free Ca2+ ([Ca2+]i) activate several kinases that are important for neuronal plasticity, including Ca2+/calmodulin-dependent kinase II (CaMKII), protein kinase A (PKA), and protein kinase C (PKC). Because it is also known, mainly in non-neuronal systems, that superoxide radicals (O2-) activate these (and other) kinases and because O2- generation by mitochondria is in part [Ca2+]i dependent, we examined in hippocampal neurons the relationship between Ca2+ entry, O2- production, and kinase activity. We found that, after large stimulus-induced [Ca2+]i increases, O2- s

Intracellular Na+ concentration influences short-term plasticity of glutamate transporter-mediated currents in neocortical astrocytes.

Fast synaptic transmission requires a rapid clearance of the released neurotransmitter from the extracellular space. Glial glutamate transporters (excitatory amino acid transporters, EAATs) strongly contribute to glutamate removal. In this work, we investigated the paired-pulse plasticity of synaptically activated, glutamate transporter-mediated currents (STCs) in cortical layer 2/3 astrocytes. STCs were elicited by local electrical stimulation in layer 4 in the presence of ionotropic glutamate (AMPA and NMDA), GABAA, and GABAB receptor antagonists. In experiments with low [Na(+)]i (5 mM) intr

Laminin-332 coordinates mechanotransduction and growth cone bifurcation in sensory neurons.

Laminin-332 is a major component of the dermo-epidermal skin basement membrane and maintains skin integrity. The transduction of mechanical force into electrical signals by sensory endings in the skin requires mechanosensitive channels. We found that mouse epidermal keratinocytes produce a matrix that is inhibitory for sensory mechanotransduction and that the active molecular component is laminin-332. Substrate-bound laminin-332 specifically suppressed one type of mechanosensitive current (rapidly adapting) independently of integrin-receptor activation. This mechanotransduction suppression cou

Activation of mu-opioid receptors excites a population of locus coeruleus-spinal neurons through presynaptic disinhibition.

The nucleus locus coeruleus (LC) plays an important role in analgesia produced by opioids and by modulation of the descending noradrenergic pathway. The functional role of micro-opioid receptors (muOR) in regulation of the excitability of spinally projecting LC neurons has not been investigated. In the present study, we tested the hypothesis that activation of presynaptic mu-opioid receptors excites a population of spinally projecting LC neurons through attenuation of gamma-aminobutyric acid (GABA)-ergic synaptic inputs. Spinally projecting LC neurons were retrogradely labeled by a fluorescent

Reduced cortical synaptic plasticity and GluR1 expression associated with fragile X mental retardation protein deficiency.

Lack of expression of the fragile X mental retardation protein (FMRP), due to silencing of the FMR1 gene, causes the Fragile X syndrome. Although FMRP was characterized previously to be an RNA binding protein, little is known about its function or the mechanisms underlying the Fragile X syndrome. Here we report that the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit, GluR1, was decreased in the cortical synapses, but not in the hippocampus or cerebellum, of FMR1 gene knockout mice. Reduced long-term potentiation (LTP) was also found in the cortex but not in the hippocam

Disturbance of the prejunctional modulation of cholinergic neurotransmission during chronic granulomatous inflammation of the mouse ileum.

The effect of chronic granulomatous inflammation of the intestine was studied on the prejunctional modulation of cholinergic nerve activity in the mouse ileum. Contractions to carbachol (0.01 - 0.3 microM) and to electrical field stimulation (EFS, 0.25 - 8 Hz) of enteric neurons were higher in inflamed ileum as compared to control ileum. However, when the neurally-mediated contractions to EFS were expressed as percentage of the direct smooth muscle contraction to carbachol, the responses to EFS were similar in control and inflamed ileum. Atropine (1 microM) abolished all contractions to EFS an

Rapid single-step induction of functional neurons from human pluripotent stem cells.

Available methods for differentiating human embryonic stem cells (ESCs) and induced pluripotent cells (iPSCs) into neurons are often cumbersome, slow, and variable. Alternatively, human fibroblasts can be directly converted into induced neuronal (iN) cells. However, with present techniques conversion is inefficient, synapse formation is limited, and only small amounts of neurons can be generated. Here, we show that human ESCs and iPSCs can be converted into functional iN cells with nearly 100% yield and purity in less than 2 weeks by forced expression of a single transcription factor. The resu

Kir4.1 channels mediate a depolarization of hippocampal astrocytes under hyperammonemic conditions in situ.

Increased ammonium (NH(4) (+) ) concentration in the brain is the prime candidate responsible for hepatic encephalopathy (HE), a serious neurological disorder caused by liver failure and characterized by disturbed glutamatergic neurotransmission and impaired glial function. We investigated the mechanisms of NH(4) (+) -induced depolarization of astrocytes in mouse hippocampal slices using whole-cell patch-clamp and potassium-selective microelectrodes. At postnatal days (P) 18-21, perfusion with 5 mM NH(4) (+) evoked a transient increase in the extracellular potassium concentration ([K(+) ](o) )