Ca2+ Channels Involved in the Generation of the Slow Afterhyperpolarization in Cultured Rat Hippocampal Pyramidal Neurons

2000 ◽  
Vol 83 (5) ◽  
pp. 2554-2561 ◽  
Author(s):  
M. Shah ◽  
D. G. Haylett
Keyword(s):  
Calcium Channels ◽  
Action Potentials ◽  
Calcium Release ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Isolated Cells ◽  
Hippocampal Pyramidal Neurons ◽  
Calcium Induced Calcium Release ◽  
Ca2 Channels ◽  
Hippocampal Pyramidal Cells

The advantages of using isolated cells have led us to develop short-term cultures of hippocampal pyramidal cells, which retain many of the properties of cells in acute preparations and in particular the ability to generate afterhyperpolarizations after a train of action potentials. Using perforated-patch recordings, both medium and slow afterhyperpolarization currents (m I AHP and s I AHP, respectively) could be obtained from pyramidal cells that were cultured for 8–15 days. The s I AHP demonstrated the kinetics and pharmacologic characteristics reported for pyramidal cells in slices. In addition to confirming the insensitivity to 100 nM apamin and 1 mM TEA, we have shown that the s I AHP is also insensitive to 100 nM charybdotoxin but is inhibited by 100 μMd-tubocurarine. Concentrations of nifedipine (10 μM) and nimodipine (3 μM) that maximally inhibit L-type calcium channels reduced the s I AHP by 30 and 50%, respectively. However, higher concentrations of nimodipine (10 μM) abolished the s I AHP, which can be partially explained by an effect on action potentials. Both nifedipine and nimodipine at maximal concentrations were found to reduce the HVA calcium current in freshly dissociated neurons to the same extent. The N-type calcium channel inhibitor, ω-conotoxin GVIA (100 nM), irreversibly inhibited the s I AHP by 37%. Together, ω-conotoxin (100 nM) and nifedipine (10 μM) inhibited the s I AHP by 70%. 10 μM ryanodine also reduced the s I AHP by 30%, suggesting a role for calcium-induced calcium release. It is concluded that activation of the s I AHP in cultured hippocampal pyramidal cells is mediated by a rise in intracellular calcium involving multiple pathways and not just entry via L-type calcium channels.

Calcium-induced calcium release and calcium buffering in retinal horizontal cells

2002 ◽  
Vol 19 (6) ◽  
pp. 713-725 ◽  
Author(s):  
EDUARDO SOLESSIO ◽  
ERIC M. LASATER
Keyword(s):  
Calcium Channels ◽  
Ampa Receptors ◽  
Intracellular Signaling ◽  
Calcium Release ◽  
Imaging Techniques ◽  
Threshold Level ◽  
Horizontal Cells ◽  
Isolated Cells ◽  
High Calcium ◽  
Calcium Induced Calcium Release

Calcium plays an integral role in intracellular signaling and process control in neurons. In the outer retina, it is a key component to the phototransduction cycle and neurotransmitter release in photoreceptor and bipolar cell terminals. It also contributes to the responses of horizontal and bipolar cells. In the dark, horizontal cells are depolarized and calcium enters via calcium permeant AMPA receptors and voltage-activated calcium channels. As a result, horizontal cells must be capable of handling high calcium loads without sustaining damage. The aim of this study was to examine the components determining the intracellular calcium levels in H2 horizontal cells in the retina of white bass. Calcium responses were evoked in isolated cells by depolarizing voltage steps and monitored by conventional imaging techniques. The responses consisted of two components: calcium entry through voltage-gated calcium channels and subsequent release from intracellular stores by calcium-induced calcium release (CICR). Under control conditions, changes in calcium levels reached 541 nM on average from a basal level of 60 nM. When release from CICR stores was blocked with ryanodine or dantrolene, calcium levels barely reached 180 nM. The threshold level needed to trigger CICR was dependent on the duration of the applied depolarization and increased in response to shorter pulses.

Specific Subtypes of GABAA Receptors Mediate Phasic and Tonic Forms of Inhibition in Hippocampal Pyramidal Neurons

2006 ◽  
Vol 96 (2) ◽  
pp. 846-857 ◽  
Author(s):  
George A. Prenosil ◽  
Edith M. Schneider Gasser ◽  
Uwe Rudolph ◽  
Ruth Keist ◽  
Jean-Marc Fritschy ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Tonic Inhibition ◽  
Mammalian Brain ◽  
Triple Mutant ◽  
Α Subunit ◽  
Hippocampal Pyramidal Neurons ◽  
Inhibitory Neurotransmitter ◽  
Ca1 Area ◽  
Hippocampal Pyramidal Cells

The main inhibitory neurotransmitter in the mammalian brain, GABA, mediates multiple forms of inhibitory signals, such as fast and slow inhibitory postsynaptic currents and tonic inhibition, by activating a diverse family of ionotropic GABAA receptors (GABAARs). Here, we studied whether distinct GABAAR subtypes mediate these various forms of inhibition using as approach mice carrying a point mutation in the α-subunit rendering individual GABAAR subtypes insensitive to diazepam without altering their GABA sensitivity and expression of receptors. Whole cell patch-clamp recordings were performed in hippocampal pyramidal cells from single, double, and triple mutant mice. Comparing diazepam effects in knock-in and wild-type mice allowed determining the contribution of α1, α2, α3, and α5 subunits containing GABAARs to phasic and tonic forms of inhibition. Fast phasic currents were mediated by synaptic α2-GABAARs on the soma and by synaptic α1-GABAARs on the dendrites. No contribution of α3- or α5-GABAARs was detectable. Slow phasic currents were produced by both synaptic and perisynaptic GABAARs, judged by their strong sensitivity to blockade of GABA reuptake. In the CA1 area, but not in the subiculum, perisynaptic α5-GABAARs contributed to slow phasic currents. In the CA1 area, the diazepam-sensitive component of tonic inhibition also involved activation of α5-GABAARs and slow phasic and tonic signals shared overlapping pools of receptors. These results show that the major forms of inhibitory neurotransmission in hippocampal pyramidal cells are mediated by distinct GABAARs subtypes.

scholarly journals Nucleolar PARP-1 Expression Is Decreased in Alzheimer’s Disease: Consequences for Epigenetic Regulation of rDNA and Cognition

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jianying Zeng ◽  
Jenny Libien ◽  
Fatima Shaik ◽  
Jason Wolk ◽  
A. Iván Hernández
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Hippocampal Pyramidal Neurons ◽  
Functional Changes ◽  
Epigenetic Regulator ◽  
Parp 1 ◽  
Sensitive Marker ◽  
Hippocampal Pyramidal Cells

Synaptic dysfunction is thought to play a major role in memory impairment in Alzheimer’s disease (AD). PARP-1 has been identified as an epigenetic regulator of plasticity and memory. Thus, we hypothesize that PARP-1 may be altered in postmortem hippocampus of individuals with AD compared to age-matched controls without neurologic disease. We found a reduced level of PARP-1 nucleolar immunohistochemical staining in hippocampal pyramidal cells in AD. Nucleolar PARP-1 staining ranged from dispersed and less intense to entirely absent in AD compared to the distinct nucleolar localization in hippocampal pyramidal neurons in controls. In cases of AD, the percentage of hippocampal pyramidal cells with nucleoli that were positive for both PARP-1 and the nucleolar marker fibrillarin was significantly lower than in controls. PARP-1 nucleolar expression emerges as a sensitive marker of functional changes in AD and suggests a novel role for PARP-1 dysregulation in AD pathology.

scholarly journals The Molecular Basis for the Calcium-Dependent Slow Afterhyperpolarization in CA1 Hippocampal Pyramidal Neurons

2021 ◽  
Vol 12 ◽  
Author(s):  
Giriraj Sahu ◽  
Ray W. Turner
Keyword(s):  
Potassium Channels ◽  
Pyramidal Neurons ◽  
Signal Transmission ◽  
Ryanodine Receptors ◽  
Pyramidal Cells ◽  
Frequency Pattern ◽  
Hippocampal Pyramidal Neurons ◽  
Calcium Dependent ◽  
Ionic Basis ◽  
Hippocampal Pyramidal Cells

Neuronal signal transmission depends on the frequency, pattern, and timing of spike output, each of which are shaped by spike afterhyperpolarizations (AHPs). There are classically three post-spike AHPs of increasing duration categorized as fast, medium and slow AHPs that hyperpolarize a cell over a range of 10 ms to 30 s. Intensive early work on CA1 hippocampal pyramidal cells revealed that all three AHPs incorporate activation of calcium-gated potassium channels. The ionic basis for a fAHP was rapidly attributed to the actions of big conductance (BK) and the mAHP to small conductance (SK) or Kv7 potassium channels. In stark contrast, the ionic basis for a prominent slow AHP of up to 30 s duration remained an enigma for over 30 years. Recent advances in pharmacological, molecular, and imaging tools have uncovered the expression of a calcium-gated intermediate conductance potassium channel (IK, KCa3.1) in central neurons that proves to contribute to the slow AHP in CA1 hippocampal pyramidal cells. Together the data show that the sAHP arises in part from a core tripartite complex between Cav1.3 (L-type) calcium channels, ryanodine receptors, and IK channels at endoplasmic reticulum-plasma membrane junctions. Work on the sAHP in CA1 pyramidal neurons has again quickened pace, with identified contributions by both IK channels and the Na-K pump providing answers to several mysteries in the pharmacological properties of the sAHP.

Different Ca2+ channels in soma and dendrites of hippocampal pyramidal neurons mediate spike-induced Ca2+ influx

1995 ◽  
Vol 73 (6) ◽  
pp. 2553-2557 ◽  
Author(s):  
B. R. Christie ◽  
L. S. Eliot ◽  
K. Ito ◽  
H. Miyakawa ◽  
D. Johnston
Keyword(s):  
Pyramidal Cell ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
High Threshold ◽  
Intracellular Recordings ◽  
Hippocampal Pyramidal Neurons ◽  
Low Threshold ◽  
Dependent Processes ◽  
Cell Somata ◽  
Ca2 Channels

1. Intracellular recordings, in conjunction with fura-2 fluorescence imaging, were used to evaluate the contribution of the different Ca2+ channel subtypes to the Ca2+ influx induced by back-propagating trains of action potentials. High-threshold channels contributed mainly to Ca2+ influx in pyramidal cell somata and proximal dendrites, whereas low-threshold and other Ni(2+)-sensitive channels played a greater role in more distal dendritic signaling. These data suggest that the different Ca2+ channel types participate in distinct physiological functions; low-threshold channels likely play a greater role in dendritic integration, whereas high-threshold channels are more important for somatic Ca(2+)-dependent processes.

A model for dendritic Ca2+ accumulation in hippocampal pyramidal neurons based on fluorescence imaging measurements

1994 ◽  
Vol 71 (3) ◽  
pp. 1065-1077 ◽  
Author(s):  
D. B. Jaffe ◽  
W. N. Ross ◽  
J. E. Lisman ◽  
N. Lasser-Ross ◽  
H. Miyakawa ◽  
...  
Keyword(s):  
Fluorescence Imaging ◽  
Action Potentials ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Na Channels ◽  
Hippocampal Pyramidal Neurons ◽  
K Channels ◽  
Voltage Gated ◽  
Synaptic Potentials ◽  
Ca2 Channels

1. High-speed fluorescence imaging was used to measure intracellular Ca2+ concentration ([Ca2+]i) changes in hippocampal neurons injected with the Ca(2+)-sensitive indicator fura-2 during intrasomatic and synaptic stimulation. The results of these experiments were used to construct a biophysical model of [Ca2+]i dynamics in hippocampal neurons. 2. A compartmental model of a pyramidal neuron was constructed incorporating published passive membrane properties of these cells, three types of voltage-gated Ca2+ channels characterized from adult hippocampal neurons, voltage-gated Na+ and K+ currents, and mechanisms for Ca2+ buffering and extrusion. 3. In hippocampal pyramidal neurons imaging of Na+ entry during electrical activity suggests that Na+ channels, at least in sufficient density to sustain action potentials, are localized in the soma and the proximal part of the apical dendritic tree. The model, which incorporates this distribution, demonstrates that action potentials attenuate steeply in passive distal dendritic compartments or distal dendritic compartments containing Ca2+ and K+ channels. This attenuation was affected by intracellular resistivity but not membrane resistivity. 4. Consistent with fluorescence imaging experiments, a non-uniform distribution of Ca2+ accumulation was generated by Ca2+ entry through voltage-gated Ca2+ channels opened by decrementally propagating Na+ action potentials. Consequently, the largest increases in [C2+]i were produced in the proximal dendrites. Distal voltage-gated Ca2+ currents were activated by broad, almost isopotential action potentials produced by reducing the overall density of K+ channels. 5. Simulations of subthreshold synaptic stimulation produced dendritic Ca2+ entry by the activation of voltage-gated Ca2+ channels. In the model these Ca2+ signals were localized near the site of synaptic input because of the attenuation of synaptic potentials with distance from the site of origin and the steep voltage-dependence of Ca2+ channel activation. 6. These simulations support the hypotheses generated from experimental evidence regarding the differential distribution of voltage-gated Ca2+ and Na+ channels in hippocampal neurons and the resulting voltage-gated Ca2+ accumulation from action and synaptic potentials.

scholarly journals Calcium-induced calcium release and type 3 ryanodine receptors modulate the slow afterhyperpolarising current, sIAHP, and its potentiation in hippocampal pyramidal neurons

2020 ◽  
Author(s):  
Angelo Tedoldi ◽  
Petra Ludwig ◽  
Gianluca Fulgenzi ◽  
Hiroshi Takeshima ◽  
Paola Pedarzani ◽  
...  
Keyword(s):  
Time Course ◽  
Calcium Release ◽  
Pyramidal Neurons ◽  
Ryanodine Receptors ◽  
Critical Role ◽  
Specific Role ◽  
Hippocampal Pyramidal Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Calcium Induced Calcium Release ◽  
Activity Dependent

AbstractThe slow afterhyperpolarising current, sIAHP, is a Ca2+-dependent current that plays an important role in the late phase of spike frequency adaptation. sIAHP is activated by voltage-gated Ca2+ channels, while the contribution of calcium from ryanodine-sensitive intracellular stores, released by calcium-induced calcium release (CICR), is controversial in hippocampal pyramidal neurons. Three types of ryanodine receptors (RyR1-3) are expressed in the hippocampus, with RyR3 showing a predominant expression in CA1 neurons. We investigated the specific role of CICR, and particularly of its RyR3-mediated component, in the regulation of the sIAHP amplitude and time course, and the activity-dependent potentiation of the sIAHP in rat and mouse CA1 pyramidal neurons.Here we report that enhancement of CICR by caffeine led to an increase in sIAHP amplitude, while inhibition of CICR by ryanodine caused a small, but significant reduction of sIAHP. Inhibition of ryanodine-sensitive Ca2+ stores by ryanodine or depletion by the SERCA pump inhibitor cyclopiazonic acid caused a substantial attenuation in the sIAHP activity-dependent potentiation in both rat and mouse CA1 pyramidal neurons. Neurons from mice lacking RyR3 receptors exhibited a sIAHP with features undistinguishable from wild-type neurons, which was similarly reduced by ryanodine. However, the lack of RyR3 receptors led to a faster and reduced activity-dependent potentiation of sIAHP.We conclude that ryanodine receptor-mediated CICR contributes both to the amplitude of the sIAHP at steady state and its activity-dependent potentiation in rat and mouse hippocampal pyramidal neurons. In particular, we show that RyR3 receptors play an essential and specific role in shaping the activity-dependent potentiation of the sIAHP. The modulation of activity-dependent potentiation of sIAHP by RyR3-mediated CICR contributes to plasticity of intrinsic neuronal excitability and is likely to play a critical role in higher cognitive functions, such as learning and memory.

scholarly journals Bayesian modeling of BAC firing as a mechanism for apical amplification in neocortical pyramidal neurons

2019 ◽  
Author(s):  
Jim W. Kay ◽  
W. A. Phillips ◽  
Jaan Aru ◽  
Bruce P. Graham ◽  
Matthew E. Larkum
Keyword(s):  
Action Potentials ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Single Site ◽  
Biophysical Model ◽  
Cellular Mechanisms ◽  
Context Sensitive ◽  
Dendritic Shaft ◽  
Current Task ◽  
Integration Sites

AbstractPyramidal cells in layer 5 of the neocortex have two distinct integration sites. These cells integrate inputs to basal dendrites in the soma while integrating inputs to the tuft in a site at the top of the apical trunk. The two sites communicate by action potentials that backpropagate to the apical site and by backpropagation-activated calcium spikes (BAC firing) that travel from the apical to the somatic site. Six key messages arise from the probabilistic information-theoretic analyses of BAC firing presented here. First, we suggest that pyramidal neurons with BAC firing could convert the odds in favour of the presence of a feature given the basal data into the odds in favour of the presence of a feature given the basal data and the apical input, by a simple Bayesian calculation. Second, the strength of the cell’s response to basal input can be amplified when relevant to the current context, as specified by the apical input, without corrupting the message that it sends. Third, these analyses show rigorously how this apical amplification depends upon communication between the sites. Fourth, we use data on action potentials from a very detailed multi-compartmental biophysical model to study our general model in a more realistic setting, and demonstrate that it describes the data well. Fifth, this form of BAC firing meets criteria for distinguishing modulatory from driving interactions that have been specified using recent definitions of multivariate mutual information. Sixth, our general decomposition can be extended to cases where, instead of being purely driving or purely amplifying, apical and basal inputs can be partly driving and partly amplifying to various extents. These conclusions imply that an advance beyond the assumption of a single site of integration within pyramidal cells is needed, and suggest that the evolutionary success of neocortex may depend upon the cellular mechanisms of context-sensitive selective amplification hypothesized here.Author summaryThe cerebral cortex has a key role in conscious perception, thought, and action, and is predominantly composed of a particular kind of neuron: the pyramidal cells. The distinct shape of the pyramidal neuron with a long dendritic shaft separating two regions of profuse dendrites allows them to integrate inputs to the two regions separately and combine the results non-linearly to produce output. Here we show how inputs to this more distant site strengthen the cell’s output when it is relevant to the current task and environment. By showing that such neurons have capabilities that transcend those of neurons with the single site of integration assumed by many neuroscientists, this ‘splitting of the neuronal atom’ offers a radically new viewpoint from which to understand the evolution of the cortex and some of its many pathologies. This also suggests that approaches to artificial intelligence using neural networks might come closer to something analogous to real intelligence, if, instead of basing them on processing elements with a single site of integration, they were based on elements with two sites, as in cortex.

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