Topic: hippocampal slices

Adenosine, through the A1 receptor (A1R), is an endogenous anticonvulsant. Development of adenosine receptor agonists as antiseizure drugs has been hampered by cardiac effects. A moderately A1R-selective agonist, MRS5474, has been reported to suppress seizures without appreciable cardiac action (Tosh et al., 2012, J Med Chem, 55:8075). We aimed at understanding its mechanism of action. MRS5474 (50-500nM) was devoid of effect upon rodent excitatory synaptic signals in hippocampal slices, except when hyperexcitability was previously induced in vivo or ex vivo. This contrasted with the effect of

Astrocytes display complex morphology ranging from multiple main processes stemming from the soma to endfeet and a myriad of leaflets that are in close contact with synapses and other cellular structures. This extended feature, which is heterogeneous across brain regions and physiological states, is pivotal to understanding their dynamic interactions with neighboring neurons and glia. Therefore, assessing astrocytic structures is crucial to understanding their roles in brain networks. Immunostaining for Glial Fibrillary Acidic Protein (GFAP), an astrocyte-specific cytoskeletal protein, is comm

Ketamine, an open-channel blocker of the N-methyl-D-aspartate receptor (NMDAR), has been shown to have rapid and sustained antidepressant effects after a single sub-anesthetic dose. Among its two enantiomers, (S)-ketamine acts more potently at NMDARs than (R)-ketamine, and its use as an antidepressant was approved by the FDA in 2019. Given that the mechanism underlying ketamine’s sustained antidepressant action remains unclear, we investigated if (S)-ketamine has any long-term effect on NMDAR-mediated synaptic transmission. In extracellular recordings from the CA1 region of mouse hippocampal s

Studies have shown that ergothioneine (ergo), a derivative of histidine synthesized by certain fungi and actinobacteria, can protect against neuronal injury induced by exogenous Aβ. Our aim is to investigate the role of ergo in synaptic plasticity using the AD mouse model. Field electrophysiology was performed in the CA1 region of hippocampal slices from male C57BL/6 mice to measure synaptic modification over time. Hippocampal slices from the double transgenic AD mouse model APP/PS1, when stimulated with a strong tetanisation protocol, exhibit impaired late long-term potentiation (late-LTP), w

Stress during adolescence is a known risk factor for neuropsychiatric disorders later in life, but how different factors alter the susceptibility to lasting cognitive or affective impairment is only partially understood. Here, we asked whether activin, a member of the TGF-β family, has a role in this process, the rationale being that activin affects the neural underpinnings of cognitive performance and affective behavior in the adult brain. We combined a mouse model of adolescent stress (corticosterone between postnatal days 30-45) with a transgenic mouse line expressing a dominant-negative mu

Alzheimer's disease (AD) is a major neurodegenerative disease characterized by a marked decline in the activity of the alpha-ketoglutarate dehydrogenase complex (AKGDHC), a key metabolite of the tricarboxylic acid (TCA) cycle. Earlier studies have shown that the calcium salt of AKG, CaAKG, increases the healthspan and lifespan in C57BL/6 mice by reducing inflammatory cytokines. Here, we demonstrate that CaAKG attenuates long-term potentiation (LTP) in an animal model of AD, APP/PS1 mice. CaAKG application during strong tetanisation converts early-LTP to late-LTP, stable for 4 hours in the CA1

Autistic spectrum disorder (ASD) has been associated with genetic alterations of synaptic proteins such as the point mutation R451C in neuroligin 3 (NLGN3), a postsynaptic adhesion molecule located at both excitatory and inhibitory synapses. By exploiting the transgenic NLGN3-R451C knock-in (KI) mice, an animal model of ASD, we investigated this mutation in the coordination of excitatory and inhibitory synaptic plasticity. In hippocampal primary cultures, while the NLGN3-R451C protein was less expressed in KI mice with respect to WT, the molecular and functional properties of basal excitatory

Ethanol (EtOH) exposure during pregnancy can induce a range of physical, learning, and behavioral disorders in the newborn clinically referred as Fetal Alcohol Spectrum Disorder (FASD). Unfortunately, FASD is poorly understood, and the underlying mechanisms are not fully known. Here, we studied the role of AMPA receptors (AMPARs) in in vitro and in vivo models of prenatal alcohol exposure (PAE). For the in vitro study, immature rat organotypic hippocampal slices were exposed to EtOH (150 mM) for 7 days followed by 24 hours of withdrawal. For the in vivo study, female C57/Bl6 mice were exposed