scholarly journals The potassium channel subunit Kvβ1 serves as a major control point for synaptic facilitation

2020 ◽  
Vol 117 (47) ◽  
pp. 29937-29947
Author(s):  
In Ha Cho ◽  
Lauren C. Panzera ◽  
Morven Chin ◽  
Scott A. Alpizar ◽  
Genaro E. Olveda ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Critical Role ◽  
Control Point ◽  
Rapid Onset ◽  
Optical Measurements ◽  
High Frequency Stimulation ◽  
Hippocampal Pyramidal Neurons ◽  
Synaptic Facilitation ◽  
Channel Inactivation

Analysis of the presynaptic action potential’s (APsyn) role in synaptic facilitation in hippocampal pyramidal neurons has been difficult due to size limitations of axons. We overcame these size barriers by combining high-resolution optical recordings of membrane potential, exocytosis, and Ca2+in cultured hippocampal neurons. These recordings revealed a critical and selective role for Kv1 channel inactivation in synaptic facilitation of excitatory hippocampal neurons. Presynaptic Kv1 channel inactivation was mediated by the Kvβ1 subunit and had a surprisingly rapid onset that was readily apparent even in brief physiological stimulation paradigms including paired-pulse stimulation. Genetic depletion of Kvβ1 blocked all broadening of the APsynduring high-frequency stimulation and eliminated synaptic facilitation without altering the initial probability of vesicle release. Thus, using all quantitative optical measurements of presynaptic physiology, we reveal a critical role for presynaptic Kvchannels in synaptic facilitation at presynaptic terminals of the hippocampus upstream of the exocytic machinery.

scholarly journals The Potassium Channel Subunit Kvβ1 is Required for Synaptic Facilitation

2020 ◽  
Author(s):  
In Ha Cho ◽  
Lauren C. Panzera ◽  
Morven Chin ◽  
Scott A. Alpizar ◽  
Michael B. Hoppa
Keyword(s):  
High Frequency ◽  
Hippocampal Neurons ◽  
Vesicle Fusion ◽  
Optical Measurements ◽  
High Frequency Stimulation ◽  
Nerve Terminals ◽  
Synaptic Facilitation ◽  
Presynaptic Action ◽  
Channel Inactivation ◽  
Frequency Stimulation

AbstractAnalysis of the presynaptic action potential’s (APsyn) role in synaptic facilitation in hippocampal pyramidal neurons has been difficult due to size limitations of axons. We overcame these size barriers by combining high resolution optical recordings of membrane potential, exocytosis and Ca2+ in cultured hippocampal neurons. These recordings revealed a critical and selective role for Kv1 channel inactivation in synaptic facilitation of excitatory hippocampal neurons. Presynaptic Kv1 channel inactivation was mediated by the Kvβ1 subunit, and had a surprisingly rapid onset that was readily apparent even in brief physiological stimulation paradigms including paired-pulse stimulation. Genetic depletion of Kvβ1 blocked all broadening of the APsyn during high frequency stimulation and eliminated synaptic facilitation without altering the initial probability of vesicle release. Thus using all quantitative optical measurements of presynaptic physiology, we reveal a critical role for presynaptic Kv channels in synaptic facilitation at small presynaptic terminals of the hippocampal neurons upstream of exocytic machinery.SignificanceNerve terminals generally engage in two opposite and essential forms of synaptic plasticity (facilitation or depression) during high frequency stimulation that play critical roles in learning and memory. Measurements of the electrical impulses (action potentials) underlying these two forms of plasticity has been difficult in small nerve terminals due to their size. In this study we deployed a combination of optical measurements of vesicle fusion and membrane voltage to overcome this previous size barrier. Here, we found a unique molecular composition of Kv1 channel β-subunits that causes broadening of the presynaptic action essential to synaptic facilitation. Disruption of the Kvβ1 inactivation mechanism switches excitatory nerve terminals into a depressive state, without any disruption to initial probability of vesicle fusion.

Two Mechanisms That Raise Free Intracellular Calcium in Rat Hippocampal Neurons During Hypoosmotic and Low NaCl Treatment

2000 ◽  
Vol 83 (1) ◽  
pp. 81-89 ◽  
Author(s):  
Aren J. Borgdorff ◽  
George G. Somjen ◽  
Wytse J. Wadman
Keyword(s):  
Synaptic Transmission ◽  
Intracellular Calcium ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Cell Swelling ◽  
Tissue Slices ◽  
Extracellular Medium ◽  
Calcium Activity ◽  
Hippocampal Pyramidal Neurons

Previous studies have shown that exposing hippocampal slices to low osmolarity (πo) or to low extracellular NaCl concentration ([NaCl]o) enhances synaptic transmission and also causes interstitial calcium ([Ca2+]o) to decrease. Reduction of [Ca2+]o suggests cellular uptake and could explain the potentiation of synaptic transmission. We measured intracellular calcium activity ([Ca2+]i) using fluorescent indicator dyes. In CA1 hippocampal pyramidal neurons in tissue slices, lowering πo by ∼70 mOsm caused “resting” [Ca2+]i as well as synaptically or directly stimulated transient increases of calcium activity (Δ[Ca2+]i) to transiently decrease and then to increase. In dissociated cells, lowering πo by ∼70 mOsm caused [Ca2+]i to almost double on average from 83 to 155 nM. The increase of [Ca2+]i was not significantly correlated with hypotonic cell swelling. Isoosmotic (mannitol- or sucrose-substituted) lowering of [NaCl]o, which did not cause cell swelling, also raised [Ca2+]i. Substituting NaCl with choline-Cl or Na-methyl-sulfate did not affect [Ca2+]i. In neurons bathed in calcium-free medium, lowering πo caused a milder increase of [Ca2+]i, which was correlated with cell swelling, but in the absence of external Ca2+, isotonic lowering of [NaCl]o triggered only a brief, transient response. We conclude that decrease of extracellular ionic strength (i.e., in both low πo and low [NaCl]o) causes a net influx of Ca2+ from the extracellular medium whereas cell swelling, or the increase in membrane tension, is a signal for the release of Ca2+ from intracellular stores.

scholarly journals GluA4 subunit of AMPA receptors mediates the early synaptic response to altered network activity in the developing hippocampus

2016 ◽  
Vol 115 (6) ◽  
pp. 2989-2996 ◽  
Author(s):  
J. Huupponen ◽  
T. Atanasova ◽  
T. Taira ◽  
S. E. Lauri
Keyword(s):  
Ampa Receptors ◽  
Pyramidal Neurons ◽  
Activity Patterns ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Postnatal Period ◽  
Homeostatic Plasticity ◽  
Network Activity ◽  
Hippocampal Pyramidal Neurons ◽  
Activity Dependent

Development of the neuronal circuitry involves both Hebbian and homeostatic plasticity mechanisms that orchestrate activity-dependent refinement of the synaptic connectivity. AMPA receptor subunit GluA4 is expressed in hippocampal pyramidal neurons during early postnatal period and is critical for neonatal long-term potentiation; however, its role in homeostatic plasticity is unknown. Here we show that GluA4-dependent plasticity mechanisms allow immature synapses to promptly respond to alterations in network activity. In the neonatal CA3, the threshold for homeostatic plasticity is low, and a 15-h activity blockage with tetrodotoxin triggers homeostatic upregulation of glutamatergic transmission. On the other hand, attenuation of the correlated high-frequency bursting in the CA3-CA1 circuitry leads to weakening of AMPA transmission in CA1, thus reflecting a critical role for Hebbian synapse induction in the developing CA3-CA1. Both of these developmentally restricted forms of plasticity were absent in GluA4 −/− mice. These data suggest that GluA4 enables efficient homeostatic upscaling and responsiveness to temporal activity patterns during the critical period of activity-dependent refinement of the circuitry.

scholarly journals Small-conductance Ca2+-activated K+ channels modulate action potential-induced Ca2+ transients in hippocampal neurons

2013 ◽  
Vol 109 (6) ◽  
pp. 1514-1524 ◽  
Author(s):  
Raffaella Tonini ◽  
Teresa Ferraro ◽  
Marisol Sampedro-Castañeda ◽  
Anna Cavaccini ◽  
Martin Stocker ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Apical Dendrite ◽  
Channel Blockers ◽  
Sk Channels ◽  
Hippocampal Pyramidal Neurons ◽  
Voltage Gated ◽  
Small Conductance

In hippocampal pyramidal neurons, voltage-gated Ca2+ channels open in response to action potentials. This results in elevations in the intracellular concentration of Ca2+ that are maximal in the proximal apical dendrites and decrease rapidly with distance from the soma. The control of these action potential-evoked Ca2+ elevations is critical for the regulation of hippocampal neuronal activity. As part of Ca2+ signaling microdomains, small-conductance Ca2+-activated K+ (SK) channels have been shown to modulate the amplitude and duration of intracellular Ca2+ signals by feedback regulation of synaptically activated Ca2+ sources in small distal dendrites and dendritic spines, thus affecting synaptic plasticity in the hippocampus. In this study, we investigated the effect of the activation of SK channels on Ca2+ transients specifically induced by action potentials in the proximal processes of hippocampal pyramidal neurons. Our results, obtained by using selective SK channel blockers and enhancers, show that SK channels act in a feedback loop, in which their activation by Ca2+ entering mainly through L-type voltage-gated Ca2+ channels leads to a reduction in the subsequent dendritic influx of Ca2+. This underscores a new role of SK channels in the proximal apical dendrite of hippocampal pyramidal neurons.

scholarly journals Transient oxytocin signaling primes the development and function of excitatory hippocampal neurons

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Silvia Ripamonti ◽  
Mateusz C Ambrozkiewicz ◽  
Francesca Guzzi ◽  
Marta Gravati ◽  
Gerardo Biella ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Hippocampal Pyramidal Neurons ◽  
Excitatory Transmission ◽  
Oxytocin Receptors ◽  
Synapse Density ◽  
Protein Components ◽  
And Function

Beyond its role in parturition and lactation, oxytocin influences higher brain processes that control social behavior of mammals, and perturbed oxytocin signaling has been linked to the pathogenesis of several psychiatric disorders. However, it is still largely unknown how oxytocin exactly regulates neuronal function. We show that early, transient oxytocin exposure in vitro inhibits the development of hippocampal glutamatergic neurons, leading to reduced dendrite complexity, synapse density, and excitatory transmission, while sparing GABAergic neurons. Conversely, genetic elimination of oxytocin receptors increases the expression of protein components of excitatory synapses and excitatory synaptic transmission in vitro. In vivo, oxytocin-receptor-deficient hippocampal pyramidal neurons develop more complex dendrites, which leads to increased spine number and reduced γ-oscillations. These results indicate that oxytocin controls the development of hippocampal excitatory neurons and contributes to the maintenance of a physiological excitation/inhibition balance, whose disruption can cause neurobehavioral disturbances.

Effect of Gastrodin on Cognitive Dysfunction in Diabetes by Inhibiting PAK2 Phosphorylation

2021 ◽  
Author(s):  
Zhi-Hao Mu ◽  
Zhi-Min Zhao ◽  
Su-Su Yang ◽  
Lei Zhou ◽  
Zhong-Yi Qian ◽  
...  
Keyword(s):  
Western Blot ◽  
Cognitive Dysfunction ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Transcriptional Analysis ◽  
Hippocampal Pyramidal Neurons ◽  
Potential Factors ◽  
P21 Activated Kinase

Abstract Diabetes and cognitive dysfunction are highly prevalent disorders, while the underlying mechanism is still elusive. The effects of Gastrodin on central nervous system have been emphasized recently. In this study, we aim to explore the potential mechanism leading to cognitive dysfunction in diabetes and the therapeutic effect of Gastrodin. Diabetes was induced by a single injection of streptozotocin. RNA sequencing technique was used to identify the potential factors involved. Western blot and immunofluorescence were applied to detect the protein expression. Our results have shown that spatial learning was impaired and hippocampal pyramidal neurons were damaged in diabetic rats, which could be ameliorated by Gastrodin intervention. Transcriptional analysis identified differential expression genes, which were confirmed by qPCR and western blot. Furthermore, p21 activated kinase 2 (PAK2) was selected and its inhibitor could promote the survival of primary hippocampal neurons. It suggested that PAK2 pathway may be involved in cognitive dysfunction in diabetes and a therapeutic target for Gastrodin intervention.

scholarly journals Distance-dependent regulation of NMDAR nanoscale organization along hippocampal neuron dendrites

2020 ◽  
Vol 117 (39) ◽  
pp. 24526-24533
Author(s):  
Joana S. Ferreira ◽  
Julien P. Dupuis ◽  
Blanka Kellermayer ◽  
Nathan Bénac ◽  
Constance Manso ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Dendritic Tree ◽  
Synaptic Proteins ◽  
Glutamatergic Synapses ◽  
Action Potential Firing ◽  
Hippocampal Pyramidal Neurons ◽  
Calcium Calmodulin Dependent ◽  
Potential Firing ◽  
Nanoscale Topography

Hippocampal pyramidal neurons are characterized by a unique arborization subdivided in segregated dendritic domains receiving distinct excitatory synaptic inputs with specific properties and plasticity rules that shape their respective contributions to synaptic integration and action potential firing. Although the basal regulation and plastic range of proximal and distal synapses are known to be different, the composition and nanoscale organization of key synaptic proteins at these inputs remains largely elusive. Here we used superresolution imaging and single nanoparticle tracking in rat hippocampal neurons to unveil the nanoscale topography of native GluN2A- and GluN2B-NMDA receptors (NMDARs)—which play key roles in the use-dependent adaptation of glutamatergic synapses—along the dendritic arbor. We report significant changes in the nanoscale organization of GluN2B-NMDARs between proximal and distal dendritic segments, whereas the topography of GluN2A-NMDARs remains similar along the dendritic tree. Remarkably, the nanoscale organization of GluN2B-NMDARs at proximal segments depends on their interaction with calcium/calmodulin-dependent protein kinase II (CaMKII), which is not the case at distal segments. Collectively, our data reveal that the nanoscale organization of NMDARs changes along dendritic segments in a subtype-specific manner and is shaped by the interplay with CaMKII at proximal dendritic segments, shedding light on our understanding of the functional diversity of hippocampal glutamatergic synapses.

scholarly journals Activation of InsP3 receptors is sufficient for inducing graded intrinsic plasticity in rat hippocampal pyramidal neurons

2015 ◽  
Vol 113 (7) ◽  
pp. 2002-2013 ◽  
Author(s):  
Sufyan Ashhad ◽  
Daniel Johnston ◽  
Rishikesh Narayanan
Keyword(s):  
Neural Coding ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Neuronal Response ◽  
Input Resistance ◽  
Response Dynamics ◽  
Resonance Strength ◽  
Hippocampal Pyramidal Neurons ◽  
Calcium Dependent ◽  
Intrinsic Plasticity

The synaptic plasticity literature has focused on establishing necessity and sufficiency as two essential and distinct features in causally relating a signaling molecule to plasticity induction, an approach that has been surprisingly lacking in the intrinsic plasticity literature. In this study, we complemented the recently established necessity of inositol trisphosphate (InsP3) receptors (InsP3R) in a form of intrinsic plasticity by asking if InsP3R activation was sufficient to induce intrinsic plasticity in hippocampal neurons. Specifically, incorporation of d-myo-InsP3 in the recording pipette reduced input resistance, maximal impedance amplitude, and temporal summation but increased resonance frequency, resonance strength, sag ratio, and impedance phase lead. Strikingly, the magnitude of plasticity in all these measurements was dependent on InsP3 concentration, emphasizing the graded dependence of such plasticity on InsP3R activation. Mechanistically, we found that this InsP3-induced plasticity depended on hyperpolarization-activated cyclic nucleotide-gated channels. Moreover, this calcium-dependent form of plasticity was critically reliant on the release of calcium through InsP3Rs, the influx of calcium through N-methyl-d-aspartate receptors and voltage-gated calcium channels, and on the protein kinase A pathway. Our results delineate a causal role for InsP3Rs in graded adaptation of neuronal response dynamics, revealing novel regulatory roles for the endoplasmic reticulum in neural coding and homeostasis.

scholarly journals The effect of optogenetic activation of astrocytes on the hippocampal neurons activity

2021 ◽  
Vol 2086 (1) ◽  
pp. 012110
Author(s):  
E I Gerasimov ◽  
A I Erofeev ◽  
S A Pushkareva ◽  
A V Bol’shakova ◽  
A A Borodinova ◽  
...  
Keyword(s):  
Temporal Resolution ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Cellular Activity ◽  
Hippocampal Pyramidal Neurons ◽  
The Past ◽  
Optogenetic Stimulation ◽  
Stimulation Parameters ◽  
The Future ◽  
Stimulation Of

Abstract The method of optogenetics has spread widely in neurobiology over the past 10 years and has found extensive application in various fields of this sciences. It allows to control and regulate cellular activity with high spatial and temporal resolution. In this study, optogenetic activation was applied to astrocytes expressing ChR2. Optogenetic stimulation parameters were determined, in which the frequency of spontaneous currents of hippocampal pyramidal neurons significantly changed. In the future, it is planned to use the obtained data on the modes of optogenetic stimulation of astrocytes to normalize the functions of the hippocampus in mice-models of Alzheimer’s disease.

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