Ca2+ and filopodial responses to glutamate in cultured astrocytes and neurons

1992 ◽  
Vol 70 (S1) ◽  
pp. S206-S218 ◽  
Author(s):  
A. H. Cornell-Bell ◽  
P. G. Thomas ◽  
J. M. Caffrey
Keyword(s):  
Primary Culture ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Inorganic Ions ◽  
Apical Surface ◽  
Neuronal Responses ◽  
Ca1 Neurons ◽  
Cultured Astrocytes ◽  
Intracellular Ca ◽  
Ca3 Neurons

Neurons and glia exhibit complex homeostatic interactions via shared extracellular space which can involve metabolites, inorganic ions, and neurotransmitters. Focal application of glutamate to both human and rat central nervous system astrocytes in primary culture produced a rapid, transient increase in both cytoplasmic and nuclear Ca2+. These Ca2+ waves can propagate at up to 15–20 μm/s for long distances (millimetres) through the astrocyte syncitium. Oscillatory Ca2+ signals were frequently observed under control conditions and were enhanced by glutamate application. These Ca2+ signals were paralleled by rapid extensions of filopodia from the astrocyte cell margin and apical surface near the point of glutamate application. Focal application of glutamate to rat hippocampal neurons also elicited rapid, transient increases in intracellular Ca2+. Levels of Ca2+ signals were consistently two- to three-fold greater in pyramidal neurons cultured from CA1 than in those from CA3. Filopodial extension was extensive in CA1 neurons, but rare in CA3 neurons, and in either case observable only during the first few days of primary culture. Diversity of glial and neuronal responses to binding the glutamate receptors may reflect their roles in homeostatic interactions.Key words: glutamate, astrocytes, hippocampal neurons, Ca2+ signals, filopodia.

scholarly journals Early Ischemia Enhances Action Potential-Dependent, Spontaneous Glutamatergic Responses in CA1 Neurons

2009 ◽  
Vol 30 (3) ◽  
pp. 555-565 ◽  
Author(s):  
Hui Ye ◽  
Shirin Jalini ◽  
Liang Zhang ◽  
Milton Charlton ◽  
Peter L Carlen
Keyword(s):  
Action Potential ◽  
Pyramidal Neurons ◽  
Glutamate Release ◽  
Brain Slices ◽  
Spontaneous Release ◽  
Ca1 Neurons ◽  
Relative Contribution ◽  
Hippocampal Ca1 ◽  
Ca3 Neurons

Two types of quantal spontaneous neurotransmitter release are present in the nervous system, namely action potential (AP)-dependent release and AP-independent release. Previous studies have identified and characterized AP-independent release during hypoxia and ischemia. However, the relative contribution of AP-dependent spontaneous release to the overall glutamate released during transient ischemia has not been quantified. Furthermore, the neuronal activity that mediates such release has not been identified. Using acute brain slices, we show that AP-dependent release constitutes approximately one-third of the overall glutamate-mediated excitatory postsynaptic potentials/currents (EPSPs/EPSCs) measured onto hippocampal CA1 pyramidal neurons. However, during transient (2 mins) in vitro hypoxia–hypoglycemia, large-amplitude, AP-dependent spontaneous release is significantly enhanced and contributes to 74% of the overall glutamatergic responses. This increased AP-dependent release is due to hyper-excitability in the presynaptic CA3 neurons, which is mediated by the activity of NMDA receptors. Spontaneous glutamate release during ischemia can lead to excitotoxicity and perturbation of neural network functions.

scholarly journals Calcium Movement in Ischemia-Tolerant Hippocampal CA1 Neurons after Transient Forebrain Ischemia in Gerbils

1996 ◽  
Vol 16 (5) ◽  
pp. 915-922 ◽  
Author(s):  
Shinsuke Ohta ◽  
Shigeru Furuta ◽  
Ichiro Matsubara ◽  
Keiji Kohno ◽  
Yoshiaki Kumon ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Neuronal Death ◽  
Pyramidal Neurons ◽  
Forebrain Ischemia ◽  
Electron Microscopic ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Before And After ◽  
Intracellular Ca

Hippocampal CA1 neurons exposed to a nonlethal period (2 min) of ischemia, acquired tolerance to a subsequent lethal 5-min period of ischemia, which usually causes delayed-type neuronal death. Intracelluar Ca2+ movements before and after the 5 min of forebrain ischemia were evaluated in gerbil hippocampal CA1 pyramidal neurons, had acquired tolerance in comparison with nonischemia-tolerant CA1 neurons. Evaluation was performed by observing the ultrastructural intracellular Ca2+ distribution and the Ca2+ adenosine triphosphatase (Ca2+-ATPase) activity using electron microscopic cytochemistry. In comparison with nonischemia-tolerant CA1 neurons, mitochondria of ischemia-tolerant CA1 neurons sequestered more Ca2+ from the cytosomal fraction 15 min after the 5-min period of ischemia, and Ca2+ deposits in these mitochondria were rapidly decreased. Plasma membrane Ca2+-ATPase activities were already significantly elevated before the 5 min of ischemia, and remained at a higher level subsequently compared to nonischemia-tolerant CA1 neurons. Changes in the mitochondrial Ca2+ distribution and Ca2+-ATPase activities in ischemia-tolerant CA1 neurons after the 5-min period of ischemia showed a strong resemblance to those in CA3 neurons, which originally possess resistance to such periods of ischemia. These findings suggest that enhanced or maintained activities of mitochondrial Ca2+ sequestration and plasma membrane Ca2+-ATPase reduced Ca2+ toxicity following 5-min ischemia in terms of time, resulting in escape from delayed neuronal death.

Role of EPSPs in initiation of spontaneous synchronized burst firing in rat hippocampal neurons bathed in high potassium

1990 ◽  
Vol 64 (3) ◽  
pp. 1000-1008 ◽  
Author(s):  
N. L. Chamberlin ◽  
R. D. Traub ◽  
R. Dingledine
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Burst Firing ◽  
Interictal Spikes ◽  
High Potassium ◽  
Synaptic Excitation ◽  
Ca3 Neurons

1. Spontaneous discharges that resemble interictal spikes arise in area CA3 b/c of rat hippocampal slices bathed in 8.5 mM [K+]o. Excitatory postsynaptic potentials (EPSPs) also appear at irregular intervals in these cells. The role of local synaptic excitation in burst initiation was examined with intracellular and extracellular recordings from CA3 pyramidal neurons. 2. Most (70%) EPSPs were small (less than 2 mV in amplitude), suggesting that they were the product of quantal release or were evoked by a single presynaptic action potential in another cell. It is unlikely that most EPSPs were evoked by a presynaptic burst of action potentials. Indeed, intrinsic burst firing was not prominent in CA3 b/c pyramidal cells perfused in 8.5 mM [K+]o. 3. The likelihood of occurrence and the amplitude of EPSPs were higher in the 50-ms interval just before the onset of each burst than during a similar interval 250 ms before the burst. This likely reflects increased firing probability of CA3 neurons as they emerge from the afterhyperpolarization (AHP) and conductance shunt associated with the previous burst. 4. Perfusion with 2 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a potent quisqualate receptor antagonist, decreased the frequency of EPSPs in CA3 b/c neurons from 3.6 +/- 0.9 to 0.9 +/- 0.3 (SE) Hz. Likewise, CNQX reversibly reduced the amplitude of evoked EPSPs in CA3 b/c cells. 5. Spontaneous burst firing in 8.5 mM [K+]o was abolished in 11 of 31 slices perfused with 2 microM CNQX.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer simulations of morphologically reconstructed CA3 hippocampal neurons

1995 ◽  
Vol 73 (3) ◽  
pp. 1157-1168 ◽  
Author(s):  
M. Migliore ◽  
E. P. Cook ◽  
D. B. Jaffe ◽  
D. A. Turner ◽  
D. Johnston
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Fluorescent Imaging ◽  
Detailed Model ◽  
K Channels ◽  
Ionic Conductances ◽  
Ca3 Neurons ◽  
Firing Characteristics ◽  
Ca2 Channels ◽  
Stimulation Of

1. We tested several hypotheses with respect to the mechanisms and processes that control the firing characteristics and determine the spatial and temporal dynamics of intracellular Ca2+ in CA3 hippocampal neurons. In particular, we were interested to know 1) whether bursting and nonbursting behavior of CA3 neurons could be accounted for in a morphologically realistic model using a number of the known ionic conductances; 2) whether such a model is robust across different cell morphologies; 3) whether some particular nonuniform distribution of Ca2+ channels is required for bursting; and 4) whether such a model can reproduce the magnitude and spatial distribution of intracellular Ca2+ transients determined from fluorescence imaging studies and can predict reasonable intracellular Ca2+ concentration ([Ca2+]i) distribution for CA3 neurons. 2. For this purpose we have developed a highly detailed model of the distribution and densities of membrane ion channels in hippocampal CA3 bursting and nonbursting pyramidal neurons. This model reproduces both the experimentally observed firing modes and the dynamics of intracellular Ca2+. 3. The kinetics of the membrane ionic conductances are based on available experimental data. This model incorporates a single Na+ channel, three Ca2+ channels (CaN, CaL, and CaT), three Ca(2+)-independent K+ channels (KDR, KA, and KM), two Ca(2+)-dependent K+ channels (KC and KAHP), and intracellular Ca(2+)-related processes such as buffering, pumping, and radial diffusion. 4. To test the robustness of the model, we applied it to six different morphologically accurate reconstructions of CA3 hippocampal pyramidal neurons. In every neuron, Ca2+ channels, Ca(2+)-related processes, and Ca(2+)-dependent K+ channels were uniformly distributed over the entire cell. Ca(2+)-independent K+ channels were placed on the soma and the proximal apical dendrites. For each reconstructed cell we were able to reproduce bursting and nonbursting firing characteristics as well as Ca2+ transients and distributions for both somatic and synaptic stimulations. 5. Our simulation results suggest that CA3 pyramidal cell bursting behavior does not require any special distribution of Ca(2+)-dependent channels and mechanisms. Furthermore, a simple increase in the Ca(2+)-independent K+ conductances is sufficient to change the firing mode of our CA3 neurons from bursting to nonbursting. 6. The model also displays [Ca2+]i transients and distributions that are consistent with fluorescent imaging data. Peak [Ca2+]i distribution for synaptic stimulation of the nonbursting model is broader when compared with somatic stimulation. Somatic stimulation of the bursting model shows a broader distribution in [Ca2+]i when compared with the nonbursting model.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Delayed Neuronal Recovery and Neuronal Death in Rat Hippocampus following Severe Cerebral Ischemia: Possible Relationship to Abnormalities in Neuronal Processes

1984 ◽  
Vol 4 (2) ◽  
pp. 194-205 ◽  
Author(s):  
C. K. Petito ◽  
W. A. Pulsinelli
Keyword(s):  
Endoplasmic Reticulum ◽  
Cerebral Ischemia ◽  
Hippocampal Neurons ◽  
Smooth Endoplasmic Reticulum ◽  
Light And Electron Microscopy ◽  
Rat Hippocampus ◽  
Cell Recovery ◽  
Ca1 Neurons ◽  
Neuronal Processes ◽  
Ca3 Neurons

Mechanisms involved in the postischemic delay in neuronal recovery or death in rat hippocampus were evaluated by light and electron microscopy at 3, 15, 30, and 120 min and 24, 36, 48, and 72 h following severe cerebral ischemia that was produced by permanent occlusion of the vertebral arteries and 30-min occlusion of the common carotid arteries. During the early postischemic period, neurons in the Ca1 and Ca3 regions both showed transient mitochondrial swelling followed by the disaggregation of polyribosomes, decrease in rough endoplasmic reticulum (RER), loss of Golgi apparatus (GA) cisterns, and decrease in GA vesicles. Recovery of these organelles in Ca3 neurons was first noted between 24 and 36 h and was accompanied by a marked proliferation of smooth endoplasmic reticulum (SER). Many Ca1 neurons initially recovered between 24 and 36 h, but subsequent cell death at 48–72 h was often preceded by peripheral chromatolysis, constriction and shrinkage of the proximal dendrites, and cytoplasmic dilatation that was continuous with focal expansion of RER cisterns. Because SER accumulates in resistant Ca3 neurons and proximal neuronal processes are damaged in vulnerable Ca1 neurons, we hypothesize that delayed cell recovery or death in vulnerable and resistant postischemic hippocampal neurons is related to abnormalities in neuronal processes.

scholarly journals Redox Sensitive Calcium Stores Underlie Enhanced After Hyperpolarization of Aged Neurons: Role for Ryanodine Receptor Mediated Calcium Signaling

2010 ◽  
Vol 104 (5) ◽  
pp. 2586-2593 ◽  
Author(s):  
Karthik Bodhinathan ◽  
Ashok Kumar ◽  
Thomas C. Foster
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Slow Component ◽  
Ryanodine Receptors ◽  
Calcium Stores ◽  
Memory Decline ◽  
Ca1 Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Age Related ◽  
Intracellular Ca

A decrease in the excitability of CA1 pyramidal neurons contributes to the age related decrease in hippocampal function and memory decline. Decreased neuronal excitability in aged neurons can be observed as an increase in the Ca2+- activated K+- mediated post burst afterhyperpolarization (AHP). In this study, we demonstrate that the slow component of AHP (sAHP) in aged CA1 neurons (aged-sAHP) is decreased ∼50% by application of the reducing agent dithiothreitol (DTT). The DTT-mediated decrease in the sAHP was age specific, such that it was observed in CA1 pyramidal neurons of aged (20–25 mo), but not young (6–9 mo) F344 rats. The effect of DTT on the aged-sAHP was blocked following depletion of intracellular Ca2+ stores (ICS) by thapsigargin or blockade of ryanodine receptors (RyRs) by ryanodine, suggesting that the age-related increase in the sAHP was due to release of Ca2+ from ICS through redox sensitive RyRs. The DTT-mediated decrease in the aged-sAHP was not blocked by inhibition of L-type voltage gated Ca2+ channels (L-type VGCC), inhibition of Ser/Thr kinases, or inhibition of the large conductance BK potassium channels. The results add support to the idea that a shift in the intracellular redox state contributes to Ca2+ dysregulation during aging.

scholarly journals BDNF Induces Calcium Elevations Associated With IBDNF, a Nonselective Cationic Current Mediated by TRPC Channels

2007 ◽  
Vol 98 (4) ◽  
pp. 2476-2482 ◽  
Author(s):  
Michelle D. Amaral ◽  
Lucas Pozzo-Miller
Keyword(s):  
Hippocampal Neurons ◽  
Transient Receptor Potential ◽  
Pyramidal Neurons ◽  
Receptor Potential ◽  
Trpc Channels ◽  
Hippocampal Pyramidal Neurons ◽  
Cationic Current ◽  
Intracellular Ca ◽  
Transient Receptor ◽  
Nonselective Cationic Current

Brain-derived neurotrophic factor (BDNF) has potent actions on hippocampal neurons, but the mechanisms that initiate its effects are poorly understood. We report here that localized BDNF application to apical dendrites of CA1 pyramidal neurons evoked transient elevations in intracellular Ca2+ concentration, which are independent of membrane depolarization and activation of N-methyl-d-aspartate receptors (NMDAR). These Ca2+ signals were always associated with IBDNF, a slow and sustained nonselective cationic current mediated by transient receptor potential canonical (TRPC3) channels. BDNF-induced Ca2+ elevations required functional Trk and inositol-tris-phosphate (IP3) receptors, full intracellular Ca2+ stores as well as extracellular Ca2+, suggesting the involvement of TRPC channels. Indeed, the TRPC channel inhibitor SKF-96365 prevented BDNF-induced Ca2+ elevations and the associated IBDNF. Thus TRPC channels emerge as novel mediators of BDNF-induced intracellular Ca2+ elevations associated with sustained cationic membrane currents in hippocampal pyramidal neurons.

scholarly journals IQ-Motif Proteins Influence Intracellular Free Ca2+ in Hippocampal Neurons Through Their Interactions With Calmodulin

2008 ◽  
Vol 99 (1) ◽  
pp. 264-276 ◽  
Author(s):  
Yoshihisa Kubota ◽  
John A. Putkey ◽  
Harel Z. Shouval ◽  
M. Neal Waxham
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Compartment Model ◽  
Buffering Capacity ◽  
Imaging Data ◽  
Iq Motif ◽  
Single Compartment Model ◽  
Intracellular Ca ◽  
Extrusion Mechanism ◽  
High Concentrations

Calmodulin (CaM) is most recognized for its role in activating Ca2+–CaM-dependent enzymes following increased intracellular Ca2+. However, CaM's high intracellular concentration indicates CaM has the potential to play a significant role as a Ca2+ buffer. Neurogranin (Ng) is a small neuronal IQ-motif–containing protein that accelerates Ca2+ dissociation from CaM. In cells that contain high concentrations of both Ng and CaM, like CA1 pyramidal neurons, we hypothesize that the accelerated Ca2+ dissociation from CaM by Ng decreases the buffering capacity of CaM and thereby shapes the transient dynamics of intracellular free Ca2+. We examined this hypothesis using a mathematical model constructed on the known biochemistry of Ng and confirmed the simulation results with Ca2+ imaging data in the literature. In a single-compartment model that contains no Ca2+ extrusion mechanism, Ng increased the steady-state free Ca2+. However, in the presence of a Ca2+ extrusion mechanism, Ng accelerated the decay rate of free Ca2+ through its ability to increase the Ca2+ dissociation from CaM, which in turn becomes subject to Ca2+ extrusion. Interestingly, PEP-19, another neuronal IQ-motif protein that accelerates both Ca2+ association and dissociation from CaM, appears to have the opposite impact than that of Ng on free Ca2+. As such, Ng may regulate, in addition to the Ca2+–CaM-dependent process, Ca2+-sensitive enzymes by influencing the buffering capacity of CaM and subsequently free Ca2+ levels. We examined the relative impact of these Ng-induced effects in the induction of synaptic plasticity.

scholarly journals Morphometric Analysis of Hippocampal Pyramidal Neuronsin situand in Grafts Developing in the Anterior Eye Chambers of Young and Aged Wistar Rats

1997 ◽  
Vol 6 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Z. N. Zhuravleva ◽  
V. N. Saifullina ◽  
C. I. Zenchenko
Keyword(s):  
Morphometric Analysis ◽  
Growth And Development ◽  
Wistar Rats ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Ca1 Neurons ◽  
Ca3 Pyramidal Neurons ◽  
The Mean ◽  
Ca3 Neurons

We performed a morphometric analysis of the somatic and nuclear areas in the pyramidal neurons of the hippocampal fields CA1 and CA3in situand in grafts developing for six weeks in the anterior eye chambers of young (3-to-9 wk.) and of aged (18-to-19.5 mos.) Wistar rats. The mean areas of the CA1 pyramidal somata and nuclei were significantly decreased in the aged animalsin situ. The mean parameters of the CA3 pyramidal neurons were not changed, although their distribution was different (bimodalversusunimodal in the young animals). In both groups of recipients, the areas of CA1 neurons and of their nuclei were significantly larger in the grafted tissue than those foundin situ. The areas of CA3 neurons did not show any difference in aged recipients and demonstrated only slight hypertrophy in young recipients. We concluded that the area sizes of the pyramidal cell bodies and nuclei in CA1 neurons are more sensitive than those of CA3 neurons to both aging and transplantation. The age of recipients did not significantly influence the growth and development of grafted pyramidal cells.

Effects of Pb2+ on Delayed-Rectifier Potassium Channels in Acutely Isolated Hippocampal Neurons

1997 ◽  
Vol 78 (5) ◽  
pp. 2649-2654 ◽  
Author(s):  
Michael Madeja ◽  
Ulrich Muβhoff ◽  
Norbert Binding ◽  
Ute Witting ◽  
Erwin-Josef Speckmann
Keyword(s):  
Potassium Channels ◽  
Hippocampal Neurons ◽  
Granule Cells ◽  
Potassium Currents ◽  
Delayed Rectifier ◽  
Ca1 Neurons ◽  
Current Voltage ◽  
Voltage Dependent ◽  
Ca3 Neurons ◽  
Current Voltage Relation

Madeja, Michael, Ulrich Muβhoff, Norbert Binding, Ute Witting, and Erwin-Josef Speckmann. Effects of Pb2+ on delayed-rectifier potassium channels in acutely isolated hippocampal neurons. J. Neurophysiol. 78: 2649–2654, 1997. The effects of Pb2+ on delayed-rectifier potassium currents were studied in acutely isolated hippocampal neurons (CA1 neurons, CA3 neurons, granule cells) from the guinea pig using the patch-clamp technique in the whole cell configuration. Pb2+ in micromolar concentrations decreased the potassium currents in a voltage-dependent manner, which appeared as a shift of the current-voltage relation to positive potentials. The effect was reversible after washing. The concentration-responsiveness measured in CA1 neurons revealed an IC50 value of 30 μmol/l at a potential of −30 mV. The half-maximal shift of the current-voltage relation was reached at 33 μmol/l and the maximal obtainable shift was 13.4 mV. For the different types of hippocampal neurons, the shift of the current-voltage relation was distinct and was 7.9 mV in CA1 neurons, 13.7 mV in CA3 neurons, and 14.2 mV in granule cells with 50 μmol/l Pb2+. The effects described here of Pb2+ on the potassium currents in hippocampal neurons and the differences between the types of hippocampal neurons correspond with the known properties and distributions of cloned potassium channels found in the hippocampus. As a whole, our results demonstrate that Pb2+ in micromolar concentration is a voltage-dependent, reversible blocker of delayed-rectifier potassium currents of hippocampal neurons. This effect has to be taken into consideration as a possible contributing mechanism for the neurological symptoms of enhanced brain activity seen during Pb2+ intoxication.

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