Temporal constraints in associative synaptic plasticity in hippocampus and neocortex

1995 ◽  
Vol 73 (9) ◽  
pp. 1295-1311 ◽  
Author(s):  
Dominique Debanne ◽  
Daniel E. Shulz ◽  
Yves Frégnac
Keyword(s):  
Visual Cortex ◽  
Membrane Potential ◽  
Temporal Frequency ◽  
Postsynaptic Membrane ◽  
Synaptic Potentiation ◽  
Test Input ◽  
Homosynaptic Depression ◽  
Postsynaptic Cell

We present comparative experimental evidence for the induction of synaptic potentiation and depression in organotypic cultures of hippocampus and in visual cortex in vitro and in vivo. The effects of associative pairings on the efficacy of synaptic transmission are analyzed as a function of the temporal delay between presynaptic activity and post-synaptic changes imposed in membrane potential. Synchronous association at a low temporal frequency (<0.5 Hz) between presynaptic input and postsynaptic depolarization resulted in homosynaptic potentiation of functionally identified postsynaptic potentials in the three types of preparation. Synchronous pairing of afferent activity with hyperpolarization of the postsynaptic cell resulted in homosynaptic depression in visual cortex in vivo and in vitro. An associative form of depression was induced in hippocampus when the test input was followed repeatedly with a fixed-delay postsynaptic depolarization imposed either by intracellular current injection or synaptically. The latter process might play a significant role in heterosynaptic plasticity in visual cortex in vivo and in vitro, if it is assumed that associative depression still operates in visual cortex a few seconds after the initial surge of calcium in the postsynaptic cell. We conclude that the precise timing between presynaptic activity and polarization changes in postsynaptic membrane potential up- and down-regulates the efficacy of active pathways.Key words: synaptic potentiation, synaptic depression, asynchrony, covariance, supervised learning.

scholarly journals Review of T-2307, an Investigational Agent That Causes Collapse of Fungal Mitochondrial Membrane Potential

2021 ◽  
Vol 7 (2) ◽  
pp. 130
Author(s):  
Nathan P. Wiederhold
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Candida Species ◽  
Mammalian Cells ◽  
Mitochondrial Membrane ◽  
Fungal Infections ◽  
Published Data ◽  
Candida Auris

Invasive infections caused by Candida that are resistant to clinically available antifungals are of increasing concern. Increasing rates of fluconazole resistance in non-albicans Candida species have been documented in multiple countries on several continents. This situation has been further exacerbated over the last several years by Candida auris, as isolates of this emerging pathogen that are often resistant to multiple antifungals. T-2307 is an aromatic diamidine currently in development for the treatment of invasive fungal infections. This agent has been shown to selectively cause the collapse of the mitochondrial membrane potential in yeasts when compared to mammalian cells. In vitro activity has been demonstrated against Candida species, including C. albicans, C. glabrata, and C. auris strains, which are resistant to azole and echinocandin antifungals. Activity has also been reported against Cryptococcus species, and this has translated into in vivo efficacy in experimental models of invasive candidiasis and cryptococcosis. However, little is known regarding the clinical efficacy and safety of this agent, as published data from studies involving humans are not currently available.

scholarly journals Imaging the transmembrane and transendothelial sodium gradients in gliomas

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Muhammad H. Khan ◽  
John J. Walsh ◽  
Jelena M. Mihailović ◽  
Sandeep K. Mishra ◽  
Daniel Coman ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Magnetic Resonance ◽  
Cell Membrane ◽  
Normal Tissue ◽  
Magnetic Resonance Spectroscopic Imaging ◽  
Biological Factors ◽  
High Sodium ◽  
Intracellular Milieu

AbstractUnder normal conditions, high sodium (Na+) in extracellular (Na+e) and blood (Na+b) compartments and low Na+ in intracellular milieu (Na+i) produce strong transmembrane (ΔNa+mem) and weak transendothelial (ΔNa+end) gradients respectively, and these manifest the cell membrane potential (Vm) as well as blood–brain barrier (BBB) integrity. We developed a sodium (23Na) magnetic resonance spectroscopic imaging (MRSI) method using an intravenously-administered paramagnetic polyanionic agent to measure ΔNa+mem and ΔNa+end. In vitro 23Na-MRSI established that the 23Na signal is intensely shifted by the agent compared to other biological factors (e.g., pH and temperature). In vivo 23Na-MRSI showed Na+i remained unshifted and Na+b was more shifted than Na+e, and these together revealed weakened ΔNa+mem and enhanced ΔNa+end in rat gliomas (vs. normal tissue). Compared to normal tissue, RG2 and U87 tumors maintained weakened ΔNa+mem (i.e., depolarized Vm) implying an aggressive state for proliferation, whereas RG2 tumors displayed elevated ∆Na+end suggesting altered BBB integrity. We anticipate that 23Na-MRSI will allow biomedical explorations of perturbed Na+ homeostasis in vivo.

scholarly journals Oxytocin shapes spontaneous activity patterns in the developing visual cortex by activating somatostatin interneurons

2019 ◽  
Author(s):  
Paloma P Maldonado ◽  
Alvaro Nuno-Perez ◽  
Jan Kirchner ◽  
Elizabeth Hammock ◽  
Julijana Gjorgjieva ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Spontaneous Activity ◽  
Sensory Processing ◽  
Activity Patterns ◽  
Network Activity ◽  
Synaptic Connections ◽  
Pairwise Correlations ◽  
Early Brain Development

SummarySpontaneous network activity shapes emerging neuronal circuits during early brain development, however how neuromodulation influences this activity is not fully understood. Here, we report that the neuromodulator oxytocin powerfully shapes spontaneous activity patterns. In vivo, oxytocin strongly decreased the frequency and pairwise correlations of spontaneous activity events in visual cortex (V1), but not in somatosensory cortex (S1). This differential effect was a consequence of oxytocin only increasing inhibition in V1 and increasing both inhibition and excitation in S1. The increase in inhibition was mediated by the depolarization and increase in excitability of somatostatin+ (SST) interneurons specifically. Accordingly, silencing SST+ neurons pharmacogenetically fully blocked oxytocin’s effect on inhibition in vitro as well its effect on spontaneous activity patterns in vivo. Thus, oxytocin decreases the excitatory/inhibitory ratio and modulates specific features of V1 spontaneous activity patterns that are crucial for refining developing synaptic connections and sensory processing later in life.

scholarly journals Meloxicam, a Selective COX-2 Inhibitor, Mediates Hypoxia-Inducible Factor- (HIF-) 1α Signaling in Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Yinghong Zhou ◽  
Xiaofeng Dong ◽  
Peng Xiu ◽  
Xin Wang ◽  
Jianrong Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Transcriptional Activation ◽  
Mitochondrial Membrane ◽  
Hypoxia Inducible Factor ◽  
Luciferase Assay ◽  
Cox 2

Hepatocellular carcinoma (HCC) is regarded as a leading cause of cancer-related deaths, and its progression is associated with hypoxia and the induction of hypoxia-inducible factor (HIF). Meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, induces cell death in various malignancies. However, the underlying mechanism remains to be elucidated in HCC, especially under hypoxic conditions. The alteration of COX-2 and HIF-1α oncogenicity was evaluated in HCC specimens by tissue microarray. Cell viability, angiogenesis assays, and xenografted nude mice were used to evaluate the effects of meloxicam, along with flow cytometry to detect the cell cycle, apoptosis, and mitochondrial membrane potential (ΔΨm) of HCC. qRT-PCR, Western blotting, immunofluorescence, immunohistochemistry, luciferase assay, and RNAi were carried out to determine the HIF-1α signaling affected by meloxicam. In this study, we showed that meloxicam exerts antiproliferative and antiangiogenesis efficacy in vitro and in vivo and causes disruption of mitochondrial membrane potential (ΔΨm), thus leading to caspase-dependent apoptosis under hypoxic environments. Exposure to meloxicam significantly reduced HIF-1α transcriptional activation and expression through sequestering it in the cytoplasm and accelerating degradation via increasing the von Hippel-Lindau tumor suppressor protein (pVHL) in HCC. These data demonstrated that inhibition of HIF-1α by meloxicam could suppress angiogenesis and enhance apoptosis of HCC cells. This discovery highlights that COX-2 specific inhibitors may be a promising therapy in the treatment of HCC.

Duration of NMDA-Dependent Synaptic Potentiation in Piriform Cortex In Vivo Is Increased After Epileptiform Bursting

1998 ◽  
Vol 80 (4) ◽  
pp. 1623-1629 ◽  
Author(s):  
A. Kapur ◽  
L. B. Haberly
Keyword(s):  
Seizure Activity ◽  
Piriform Cortex ◽  
Long Term Potentiation ◽  
Excitatory Postsynaptic Potential ◽  
Synaptic Potentiation ◽  
Lateral Olfactory Tract ◽  
Afferent Fibers ◽  
Stimulation Of

Kapur, A. and L. B. Haberly. Duration of NMDA-dependent synaptic potentiation in piriform cortex in vivo is increased after epileptiform bursting. J. Neurophysiol. 80: 1623–1629, 1998. Stimulation of afferent fibers with current pulse trains has been reported to induce long-term potentiation (LTP) in piriform cortex in vitro but not in vivo. LTP has been observed in vivo only when trains are paired with behavioral reinforcement and as a consequence of kindled epileptogenesis. This study was undertaken in the urethan-anesthetized rat to determine if the reported failures to observe pulse-train evoked LTP in vivo may be related to a lesser persistence rather than lack of occurrence, if disinhibition might facilitate induction, and to examine the nature of the relationship between seizure activity and LTP. Stimulation of afferent fibers in the lateral olfactory tract with θ-burst trains under control conditions potentiated the monosynaptic field excitatory postsynaptic potential (EPSP) by approximately the same extent (20.3 ± 2%; n = 12) as reported for the slice. However, in contrast to the slice, potentiation in vivo decayed to a low level within 1–2 h after induction (70% loss in 1.5 h, on average). The N-methyl-d-aspartate (NMDA)-receptor antagonists d-APV and MK-801 blocked the induction of this decremental potentiation. Pharmacological reduction of γ-aminobutyric acid–mediated inhibition at the recording site did not increase the duration of potentiation. In contrast, θ-burst stimulation applied after recovery from a period of epileptiform bursting induced stable NMDA-dependent potentiation. Mean increase in the population EPSP was approximately the same as under control conditions (21 ± 2%; n = 6), but in five of six experiments there was little or no decay in potentiation for the duration of the monitoring period (≤6 h). It is concluded that seizure activity has an enabling action on the induction of persistent synaptic potentiation by stimulus trains that bypasses the need for behavioral reinforcement.

Milk Ejection Burst-Like Electrical Activity Evoked in Supraoptic Oxytocin Neurons in Slices From Lactating Rats

2004 ◽  
Vol 91 (5) ◽  
pp. 2312-2321 ◽  
Author(s):  
Yu-Feng Wang ◽  
Glenn I. Hatton
Keyword(s):  
Membrane Potential ◽  
Firing Rate ◽  
Membrane Conductance ◽  
Peak Level ◽  
Sudden Increase ◽  
Milk Ejection ◽  
Peak Rate ◽  
Vasopressin Neurons

To examine the mechanisms underlying milk-ejection bursts of oxytocin (OT) neurons during suckling, both in vivo and in vitro studies were performed on supraoptic OT neurons from lactating rats. The bursts were first recorded extracellularly in anesthetized rats. Burst-related electrical parameters were essentially the same as previous reports except for a trend toward transient decreases in basal firing rates immediately preceding the burst. From putative OT neurons in slices with extracellular recordings, bursts that closely mimicked the in vivo bursts were elicited by phenylephrine, an α1-adrenoceptor agonist, in a low-Ca2+ medium. Moreover, in whole cell patch-clamp recordings, the in vitro bursts were recorded from immunocytochemically identified OT neurons. After a transient decrease in the basal firing rate, the in vitro bursts started with a sudden increase in the firing rate, quickly reaching a peak level, then gradually decaying, and ended with a postburst inhibition. A brief depolarization of the membrane potential and an increase in membrane conductance appeared after the onset of the burst. Spikes during a burst were characterized by a significant increase in the duration and decrease in the amplitude around the peak rate firing. These bursts were significantly different from short-lasting burst firing of vasopressin neurons in membrane potential changes, time to reach peak firing rate, spike amplitude and duration during peak rate firing. Our extensive analysis of these results suggests that the in vitro burst is a useful model for further study of mechanisms underlying milk-ejection bursts of OT neurons in vivo.

Features of Neuronal Synchrony in Mouse Visual Cortex

2003 ◽  
Vol 90 (2) ◽  
pp. 1115-1123 ◽  
Author(s):  
Gabriele Nase ◽  
Wolf Singer ◽  
Hannah Monyer ◽  
Andreas K. Engel
Keyword(s):  
Visual Cortex ◽  
Field Potential ◽  
Response Modulation ◽  
Temporal Patterning ◽  
Cellular Mechanisms ◽  
Neuronal Synchrony ◽  
Significant Difference ◽  
Random Dot Patterns

Synchronization of neuronal discharges has been hypothesized to play a role in defining cell assemblies representing particular constellations of stimulus features. In many systems and species, synchronization is accompanied by an oscillatory response modulation at frequencies in the γ-band. The cellular mechanisms underlying these phenomena of synchronization and oscillatory patterning have been studied mainly in vitro due to the difficulty in designing a direct in vivo assay. With the prospect of using conditional genetic manipulations of cortical network components, our objective was to test whether the mouse would meet the criteria to provide a model system for the study of γ-band synchrony. Multi-unit and local field potential recordings were made from the primary visual cortex of anesthetized C57BL/6J mice. Neuronal responses evoked by moving gratings, bars, and random dot patterns were analyzed with respect to neuronal synchrony and temporal patterning. Oscillations at γ-frequencies were readily evoked with all types of stimuli used. Oscillation and synchronization strength were largest for gratings and decreased when the noise level was increased in random-dot patterns. The center peak width of cross-correlograms was smallest for bars and increased with noise, yielding a significant difference between coherent random dot patterns versus patterns with 70% noise. Field potential analysis typically revealed increases of power in the γ-band during response periods. Our findings are compatible with a role for neuronal synchrony in mediating perceptual binding and suggest the usefulness of the mouse model for testing hypotheses concerning both the mechanisms and the functional role of temporal patterning.

Identification of excitatory interneurons contributing to generation of locomotion in lamprey: structure, pharmacology, and function

1989 ◽  
Vol 62 (1) ◽  
pp. 59-69 ◽  
Author(s):  
J. T. Buchanan ◽  
S. Grillner ◽  
S. Cullheim ◽  
M. Risling
Keyword(s):  
Spinal Cord ◽  
Membrane Potential ◽  
Excitatory Amino Acid ◽  
Postsynaptic Membrane ◽  
Fictive Locomotion ◽  
Potential Oscillations ◽  
And Function ◽  
Spherical Vesicles ◽  
Membrane Potential Oscillations

1. In the in vitro preparation of the lamprey spinal cord, paired intracellular recordings of membrane potential were used to identify interneurons producing excitatory postsynaptic potentials (EPSPs) on myotomal motoneurons. 2. Seventy-nine interneurons (8.4% of all neuron-motoneuron pairs tested) elicited unitary EPSPs that followed one-for-one at short, constant latencies and were therefore considered monosynaptic according to conventional criteria. Evidence was obtained for selectivity and divergence of excitatory interneuron (EIN) outputs and for convergence of EIN input to motoneurons. 3. The neurotransmitter released by EINs may be an excitatory amino acid such as glutamate, because the EPSPs were depressed by antagonists of excitatory amino acids. 4. Intracellular dye injection revealed that EINs have small cell bodies (average 11 x 27 microns), transversely oriented dendrites, and thin (less than 3 microns) slowly conducting axons (0.7 m/s) that project caudally and ipsilaterally. One EIN exhibited a system of thin multi-branching axon collaterals with periodic swellings. Ultrastructurally, these swellings contained clear spherical vesicles, and they apposed postsynaptic membrane specializations. 5. During fictive locomotion, the membrane-potential oscillations of EINs were greater in amplitude than, but similar in shape and timing to, those of their postsynaptic motoneurons. EINs fired action potentials during fictive locomotion and contributed to the depolarization of motoneurons. 6. These interneurons are proposed to be a source of excitation to motoneurons and interneurons in the lamprey spinal cord, participating in motor activity including locomotion.

Evaluation of anticancer activity in vitro and in vivo of iridium(iii) polypyridyl complexes

2019 ◽  
Vol 43 (22) ◽  
pp. 8566-8579 ◽  
Author(s):  
Miao He ◽  
Qiao-Yan Yi ◽  
Wen-Yao Zhang ◽  
Lan Bai ◽  
Fan Du ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Membrane Potential ◽  
Cytotoxic Activity ◽  
Anticancer Activity ◽  
Cell Cycle Arrest ◽  
Mitochondrial Membrane ◽  
Polypyridyl Complexes ◽  
Cycle Arrest

Three new iridium(iii) polypyridyl complexes were synthesized. The cytotoxic activity in vitro and in vivo, apoptosis, cell cycle arrest, mitochondrial membrane potential, ROS and the expression of Bcl-2 family proteins were investigated.

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