Recording Synaptic Plasticity in Acute Hippocampal Slices Maintained in a Small-volume Recycling-, Perfusion-, and Submersion-type Chamber System

Weng, Weiguang; Li, Dongxue; Peng, Cheng; Behnisch, Thomas

doi:10.3791/55936

Cited by 5 publications

(4 citation statements)

References 31 publications

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“…Acutely dissected hippocampal slices obtained from rat singles administered with vehicle or 10 mg/kg for 7h (1 h prior to brain extraction) were prepared as previously described [ 26 ], with slight modifications. Briefly, rats were anesthetized by 50 s isoflurane inhalation exposure [ 31 ], and (upon the absence of corneal reflexes), animals were decapitated using a high-precision, hardened, sharp-blade rodent guillotine (DCAP-M, World Precision Instruments, Inc., Sarasota, FL, USA). The brains were removed gently and immediately submerged in an ice-cold artificial cerebrospinal fluid (aCSF) solution of the following composition (in mM): 125 NaCl, 2.5 KCl, 20 NaHCO 3 , 2.5 CaCl 2 , 1 MgCl 2 , 25 D-glucose, and 1 NaH 2 PO 4 (pH 7.40).…”

Section: Methodsmentioning

confidence: 99%

Chirality Matters: Fine-Tuning of Novel Monoamine Reuptake Inhibitors Selectivity through Manipulation of Stereochemistry

Kalaba,

Pacher,

Neill

et al. 2023

Biomolecules

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The high structural similarity, especially in transmembrane regions, of dopamine, norepinephrine, and serotonin transporters, as well as the lack of all crystal structures of human isoforms, make the specific targeting of individual transporters rather challenging. Ligand design itself is also rather limited, as many chemists, fully aware of the synthetic and analytical challenges, tend to modify lead compounds in a way that reduces the number of chiral centers and hence limits the potential chemical space of synthetic ligands. We have previously shown that increasing molecular complexity by introducing additional chiral centers ultimately leads to more selective and potent dopamine reuptake inhibitors. Herein, we significantly extend our structure-activity relationship of dopamine transporter-selective ligands and further demonstrate how stereoisomers of defined absolute configuration may fine-tune and direct the activity towards distinct targets. From the pool of active compounds, using the examples of stereoisomers 7h and 8h, we further showcase how in vitro activity significantly differs in in vivo drug efficacy experiments, calling for proper validation of individual stereoisomers in animal studies. Furthermore, by generating a large library of compounds with defined absolute configurations, we lay the groundwork for computational chemists to further optimize and rationally design specific monoamine transporter reuptake inhibitors.

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Section: Methodsmentioning

confidence: 99%

Chirality Matters: Fine-Tuning of Novel Monoamine Reuptake Inhibitors Selectivity through Manipulation of Stereochemistry

Kalaba,

Pacher,

Neill

et al. 2023

Biomolecules

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show abstract

“…The preparation of acute hippocampal slices followed previously published methodologies (Weng et al, 2018; Yun et al, 2018). Briefly, after anaesthetization with isoflurane inhalation (4%) and decapitation, brains were immersed in ice-cold ACSF (95% O2/5% CO2 and a composition in mM: 124 NaCl, 2.5 KCl, 2.5 CaCl2, 2 MgCl2⋅6H2O, 1.25 KH2PO4, 10 glucose, 26 NaHCO3, pH 7.3–7.4).…”

Section: Methodsmentioning

confidence: 99%

Enhanced Expression of Secreted α-Klotho in the Hippocampus Alters Nesting Behavior and Memory Formation in Mice

Jing

Liu

et al. 2019

Front. Cell. Neurosci.

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The klotho gene family consists of α-, β-, and γ-Klotho, which encode type I single-pass transmembrane proteins with large extracellular domains. α-Klotho exists as a full-length membrane-bound and as a soluble form after cleavage of the extracellular domain. Due to gene splicing, a short extracellular Klotho form can be expressed and secreted. Inactivation of α-Klotho leads to a phenotype that resembles accelerated aging, as the expression level of the α-Klotho protein in the hippocampal formation of mice decreases with age. Here, we show that intrahippocampal viral expression of secreted human α-Klotho alters social behavior and memory formation. Interestingly, overexpression of secreted human α-Klotho in the CA1 changed the nest-building behavior and improved object recognition, object location and passive avoidance memory. Moreover, α-Klotho overexpression increased hippocampal synaptic transmission in response to standardized stimulation strengths, altered paired-pulse facilitation of synaptic transmission, and enhanced activity-dependent synaptic plasticity. These results indicate that memory formation benefits from an augmented level of secreted α-Klotho.

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“…A piece of the dorsal cortex was sliced off and the two hemispheres glued with the created surface on the slicing platform of the sectioning system. Transverse hippocampal slices (350 µm) were cut (Vibratome; Leica Wetzlar, Germany) and maintained in a submerged-incubation chamber for at least 2 h at room temperature (25 • C) before the transfer to a submerged-type recording chamber (RC-26GLP; Warner, Hamden, CT, USA) mounted on a Nikon (Nikon Instruments Inc., Melville, NY, USA) microscope stage (Weng et al, 2018). The slices rested for at least 30 min at 32 • C under constant perfusion with pre-carbogenated artificial cerebrospinal fluid (aCSF; 4 ml/min).…”

Section: Hippocampal Slice Preparationmentioning

confidence: 99%

Direct Medial Entorhinal Cortex Input to Hippocampal CA3 Is Crucial for eEF2K Inhibitor-Induced Neuronal Oscillations in the Mouse Hippocampus

Liu

Peng

Zhuang

et al. 2020

Front. Cell. Neurosci.

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The hippocampal formation plays a vital role in memory formation and takes part in the control of the default neuronal network activity of the brain. It also represents an important structure to analyze drug-induced effects on subregion-specific synchronization of neuronal activity. However, the consequences of an altered functional state of synapses for subregion-specific synchronization of neuronal microcircuits remain to be fully understood. Therefore, we analyzed the direct interaction of neuronal microcircuits utilizing a genetically encoded calcium sensor (GCaMP6s) and local field potential (LFP) recording in acute hippocampal-entorhinal brain slices in response to a modulator of synaptic transmission. We observed that application of the eukaryotic elongation factor-2 kinase (eEF2K) inhibitor A484954, induced a large-scale synchronization of neuronal activity within different regions of the hippocampal formation. This effect was confirmed by the recording of extracellular LFPs. Further, in order to understand if the synchronized activity depended on interconnected hippocampal areas, we lesioned adjacent regions from each other. These experiments identified the origin of A484954-induced synchronized activity in the hippocampal CA3 subfield localized near the hilus of the dentate gyrus. Remarkably, the synchronization of neuronal activity in the hippocampus required an intact connection with the medial entorhinal cortex (MEC). In line with this observation, we detected an increase in neuronal activity in the MEC area after application of A484954. In summary, inhibition of eEF2K alters the intrinsic activity of interconnected neuronal microcircuits dominated by the MEC-CA3 afferents.

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Recording Synaptic Plasticity in Acute Hippocampal Slices Maintained in a Small-volume Recycling-, Perfusion-, and Submersion-type Chamber System

Cited by 5 publications

References 31 publications

Chirality Matters: Fine-Tuning of Novel Monoamine Reuptake Inhibitors Selectivity through Manipulation of Stereochemistry

Chirality Matters: Fine-Tuning of Novel Monoamine Reuptake Inhibitors Selectivity through Manipulation of Stereochemistry

Enhanced Expression of Secreted α-Klotho in the Hippocampus Alters Nesting Behavior and Memory Formation in Mice

Direct Medial Entorhinal Cortex Input to Hippocampal CA3 Is Crucial for eEF2K Inhibitor-Induced Neuronal Oscillations in the Mouse Hippocampus

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