Calcium Signaling at Single Mossy Fiber Presynaptic Terminals in the Rat Hippocampus

2002 ◽  
Vol 87 (2) ◽  
pp. 1132-1137 ◽  
Author(s):  
Yong Liang ◽  
Li-Lian Yuan ◽  
Daniel Johnston ◽  
Richard Gray
Keyword(s):  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Imaging Techniques ◽  
Cyclopiazonic Acid ◽  
Mossy Fibers ◽  
Ruthenium Red ◽  
Experimental Conditions ◽  
Intracellular Ca ◽  
Ca3 Pyramidal Neurons ◽  
Calcium Green

We investigated internal Ca2+ release at mossy fiber synapses on CA3 pyramidal neurons (mossy fiber terminals, MFTs) in the hippocampus. Presynaptic Ca2+ influx was induced by giving a brief train of 20 stimuli at 100 Hz to the mossy fiber pathway. Using Ca2+ imaging techniques, we recorded the Ca2+ response as Δ F/ F,which increased rapidly with stimulation, but was often accompanied by a delayed peak that occurred after the train. The rise in presynaptic [Ca2+] could be completely blocked by application of 400 μM Cd2+. Furthermore, the evoked Ca2+ signals were reduced by group II mGluR agonists. Under the same experimental conditions, we investigated the effects of several agents on MFTs that disrupt regulation of intracellular Ca2+ stores resulting in depletion of internal Ca2+. We found that ryanodine, cyclopiazonic acid, thapsigargin, and ruthenium red all decreased both the early and the delayed increase in the Ca2+signals. We applied d,l-2-amino-5-phosphonovaleric acid (d,l-APV; 50 μM) and 6,7-Dinitroquinoxaline-2,3-dione (DNQX; 20 μM) to exclude the action of N-methyl-d-aspartate (NMDA) and non-NMDA receptors. Experiments with alternative lower affinity indicators for Ca2+ (fura-2FF and calcium green-2) and the transient K+ channel blocker, 4-aminopyridine were performed to control for the possible saturation of fura-2. Taken together, these results strongly support the hypothesis that the recorded terminals were from the mossy fibers of the dentate gyrus and suggest that a portion of the presynaptic Ca2+signal in response to brief trains of stimuli is due to release of Ca2+ from internal stores.

scholarly journals Calcium Dynamics in Thorny Excrescences of CA3 Pyramidal Neurons

1997 ◽  
Vol 78 (1) ◽  
pp. 10-18 ◽  
Author(s):  
David B. Jaffe ◽  
Thomas H. Brown
Keyword(s):  
Laser Scanning ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Hippocampal Slices ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
High Temporal Resolution ◽  
Calcium Dynamics ◽  
Intracellular Ca ◽  
Ca3 Pyramidal Neurons

Jaffe, David B. and Thomas H. Brown. Calcium dynamics in thorny excrescences of CA3 pyramidal neurons. J. Neurophysiol. 78: 10–18, 1997. Confocal laser scanning microscopy was used to visualize Ca2+ transients in a particular type of dendritic spine, known as a thorny excrescence, in hippocampal CA3 pyramidal neurons. These large excrescences or thorns, which serve as the postsynaptic target for the mossy-fiber synaptic inputs, were identified on the basis of their location, frequency, and size. Whole cell recordings were made from superficial CA3 pyramidal neurons in thick hippocampal slices with the use of infrared video microscopy; cells with proximal apical dendrites close to the surface of the slice were selected. Changes in intracellular Ca2+ levels were monitored by imaging changes in fluorescence of the dyes Calcium Green-1 and Fluo-3. Dual-emission fluorescence imaging was also employed with the use of a combination of Fluo-3 and the Ca2+insensitive dye seminaphthorhodafluor-1. This method was used todecrease the potential influence of background fluorescence on the calculated changes in intracellular Ca2+ concentration ([Ca2+]i). Somatic depolarization produced increases in [Ca2+]i in both the thorn and the immediately adjacent dendrite. Changes in [Ca2+]i were time locked with the onset of depolarization and the decay began immediately after the termination of depolarization. The peak increase in the Ca2+ signal was significantly greater in the thorns than in the adjacent dendritic shafts. With the use of high-temporal-resolution methods (line scans), differences were also seen in the time course of Ca2+ signals in these two regions. The decay time constants of the Ca2+ signal were faster in thorns than in the adjacent dendritic shafts. These observations suggest that voltage-gated Ca2+ channels are localized directly on the dendritic spines receiving mossy-fiber input. Furthermore, Ca2+ homeostasis within thorny excrescences is distinct from Ca2+ regulation in the dendritic shaft, at least over brief time periods, a finding that could have important implications for synaptic plasticity and signaling.

scholarly journals Action potential counting at giant mossy fiber terminals gates information transfer in the hippocampus

2018 ◽  
Vol 115 (28) ◽  
pp. 7434-7439 ◽  
Author(s):  
Simon Chamberland ◽  
Yulia Timofeeva ◽  
Alesya Evstratova ◽  
Kirill Volynski ◽  
Katalin Tóth
Keyword(s):  
Action Potential ◽  
Granule Cell ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Glutamate Release ◽  
Mossy Fibers ◽  
Action Potential Firing ◽  
Potential Firing ◽  
Ca3 Pyramidal Neurons ◽  
Calbindin D

Neuronal communication relies on action potential discharge, with the frequency and the temporal precision of action potentials encoding information. Hippocampal mossy fibers have long been recognized as conditional detonators owing to prominent short-term facilitation of glutamate release displayed during granule cell burst firing. However, the spiking patterns required to trigger action potential firing in CA3 pyramidal neurons remain poorly understood. Here, we show that glutamate release from mossy fiber terminals triggers action potential firing of the target CA3 pyramidal neurons independently of the average granule cell burst frequency, a phenomenon we term action potential counting. We find that action potential counting in mossy fibers gates glutamate release over a broad physiological range of frequencies and action potential numbers. Using rapid Ca2+ imaging we also show that the magnitude of evoked Ca2+ influx stays constant during action potential trains and that accumulated residual Ca2+ is gradually extruded on a time scale of several hundred milliseconds. Using experimentally constrained 3D model of presynaptic Ca2+ influx, buffering, and diffusion, and a Monte Carlo model of Ca2+-activated vesicle fusion, we argue that action potential counting at mossy fiber boutons can be explained by a unique interplay between Ca2+ dynamics and buffering at release sites. This is largely determined by the differential contribution of major endogenous Ca2+ buffers calbindin-D28K and calmodulin and by the loose coupling between presynaptic voltage-gated Ca2+ channels and release sensors and the relatively slow Ca2+ extrusion rate. Taken together, our results identify a previously unexplored information-coding mechanism in the brain.

Neonatal irradiation prevents the formation of hippocampal mossy fibers and the epileptic action of kainate on rat CA3 pyramidal neurons

1994 ◽  
Vol 71 (1) ◽  
pp. 204-215 ◽  
Author(s):  
J. L. Gaiarsa ◽  
L. Zagrean ◽  
Y. Ben-Ari
Keyword(s):  
Pyramidal Neurons ◽  
Gamma Ray ◽  
Mossy Fiber ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Reversal Potential ◽  
Mossy Fibers ◽  
Bath Application ◽  
Gamma Ray Irradiation ◽  
Ca3 Pyramidal Neurons

1. The effects of unilateral gamma-ray irradiation at birth on the properties of adult CA3 pyramidal neurons have been studied in hippocampal slices. 2. Neonatal gamma-ray irradiation reduced by 80% the number of granule cells and prevented the formation of mossy fiber synapses without reducing the number of CA3 pyramidal cells. The destruction of the mossy fibers was also confirmed with extracellular recordings. 3. Excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) evoked by stimulation of the stratum radiatum had similar properties in nonirradiated and irradiated hippocampi: the EPSP reversed polarity near 0 mV, was reduced in amplitude by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and D(-)-2-amino-5-phosphonovalerate (APV, 50 microM); the fast and slow IPSPs reversed at -75 and -100 mV, were blocked by bicuculline (10 microM), and reduced by phaclofen (0.5 mM), respectively. 4. Bath application of kainate (300–500 nM) evoked epileptiform activity in 81.5% of nonirradiated hippocampal CA3 regions and only in 29% of the irradiated CA3 regions. In contrast, bath application of high potassium (7 mM) and bicuculline (10 microM) generated spontaneous and evoked epileptiform activity in both nonirradiated and irradiated CA3 regions. 5. In nonirradiated and irradiated CA3 regions, kainate (200–300 nM) reduced the amplitude of the fast and slow IPSPs, reduced spike accommodation, and increased the duration of the action potential generated by a depolarizing pulse. 6. The postsynaptic responses of CA3 neurons to bath application of glutamatergic agonists were similar in nonirradiated and irradiated hippocampi in terms of amplitude, reversal potential, and pharmacology. 7. It is concluded that the most conspicuous effect of neonatal gamma-ray irradiation is to prevent the epileptic action of kainate. We propose that kainate generates epileptiform activity in the intact CA3 region by activating high-affinity binding sites located on the mossy fiber terminals.

scholarly journals Action potential counting at giant mossy fiber terminals gates information transfer in the hippocampus

2017 ◽  
Author(s):  
Simon Chamberland ◽  
Yulia Timofeeva ◽  
Alesya Evstratova ◽  
Kirill Volynski ◽  
Katalin Tóth
Keyword(s):  
Information Transfer ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
Pyramidal Cells ◽  
Short Term ◽  
Ca3 Pyramidal Neurons ◽  
Presynaptic Calcium ◽  
Ca3 Pyramidal Cells ◽  
The Brain

AbstractHippocampal mossy fibers have long been recognized as conditional detonators owing to prominent short-term facilitation, but the patterns of activity required to fire postsynaptic CA3 pyramidal neurons remain poorly understood. We show that mossy fibers count the number of spikes to transmit information to CA3 pyramidal cells through a distinctive interplay between presynaptic calcium dynamics, buffering and vesicle replenishment. This identifies a previously unexplored information coding mechanism in the brain.

scholarly journals An optogenetic method for investigating presynaptic molecular regulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuni Kay ◽  
Bruce E. Herring
Keyword(s):  
Pyramidal Neurons ◽  
Molecular Regulation ◽  
Glutamatergic Synapses ◽  
Experimental Conditions ◽  
Regulatory Pathways ◽  
Genetic Manipulations ◽  
Postsynaptic Protein ◽  
Presynaptic Function ◽  
Synaptotagmin 1 ◽  
Ca3 Pyramidal Neurons

AbstractWhile efficient methods are well established for studying postsynaptic protein regulation of glutamatergic synapses in the mammalian central nervous system, similarly efficient methods are lacking for studying proteins regulating presynaptic function. In the present study, we introduce an optical/electrophysiological method for investigating presynaptic molecular regulation. Here, using an optogenetic approach, we selectively stimulate genetically modified presynaptic CA3 pyramidal neurons in the hippocampus and measure optically-induced excitatory postsynaptic currents produced in unmodified postsynaptic CA1 pyramidal neurons. While such use of optogenetics is not novel, previous implementation methods do not allow basic quantification of the changes in synaptic strength produced by genetic manipulations. We find that incorporating simultaneous recordings of fiber volley amplitude provides a control for optical stimulation intensity and, as a result, creates a metric of synaptic efficacy that can be compared across experimental conditions. In the present study, we utilize our new method to demonstrate that inhibition of synaptotagmin 1 expression in CA3 pyramidal neurons leads to a significant reduction in Schaffer collateral synapse function, an effect that is masked with conventional electrical stimulation. Our hope is that this method will expedite our understanding of molecular regulatory pathways that govern presynaptic function.

scholarly journals Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer

2019 ◽  
Author(s):  
Nuno Apóstolo ◽  
Samuel N. Smukowski ◽  
Jeroen Vanderlinden ◽  
Giuseppe Condomitti ◽  
Vasily Rybakin ◽  
...  
Keyword(s):  
Cell Surface ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Surface Protein ◽  
Guidance Cue ◽  
Hippocampal Ca3 ◽  
Cell Surface Interactions ◽  
Ca3 Pyramidal Neurons ◽  
Ca3 Neurons ◽  
Multiple Ligand

SummarySynaptic diversity is a key feature of neural circuits. The structural and functional diversity of closely spaced inputs converging on the same neuron suggests that cell-surface interactions are essential in organizing input properties. Here, we analyzed the cell-surface protein (CSP) composition of hippocampal mossy fiber (MF) inputs on CA3 pyramidal neurons to identify regulators of MF-CA3 synapse properties. We uncover a rich cell-surface repertoire that includes adhesion proteins, guidance cue receptors, extracellular matrix (ECM) proteins, and uncharacterized CSPs. Interactome screening reveals multiple ligand-receptor modules and identifies ECM protein Tenascin-R (TenR) as a ligand of the uncharacterized neuronal receptor IgSF8. Presynaptic Igsf8 deletion impairs MF-CA3 synaptic architecture and robustly decreases the density of bouton filopodia that provide feedforward inhibition of CA3 neurons. Consequently, loss of IgSF8 increases CA3 neuron excitability. Our findings identify IgSF8 as a regulator of CA3 microcircuit development and suggest that combinations of CSP modules define input identity.

scholarly journals L-Type Calcium Channels Are Required for One Form of Hippocampal Mossy Fiber LTP

1998 ◽  
Vol 79 (4) ◽  
pp. 2181-2190 ◽  
Author(s):  
Ajay Kapur ◽  
Mark F. Yeckel ◽  
Richard Gray ◽  
Daniel Johnston
Keyword(s):  
Calcium Channels ◽  
High Frequency ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Calcium Influx ◽  
Calcium Transients ◽  
High Frequency Stimulation ◽  
Frequency Stimulation ◽  
Ca3 Pyramidal Neurons ◽  
Postsynaptic Calcium

Kapur, Ajay, Mark F. Yeckel, Richard Gray, and Daniel Johnston. L-type calcium channels are required for one form of hippocampal mossy fiber LTP. J. Neurophysiol. 79: 2181–2190, 1998. The requirement of postsynaptic calcium influx via L-type channels for the induction of long-term potentiation (LTP) of mossy fiber input to CA3 pyramidal neurons was tested for two different patterns of stimulation. Two types of LTP-inducing stimuli were used based on the suggestion that one of them, brief high-frequency stimulation (B-HFS), induces LTP postsynaptically, whereas the other pattern, long high-frequency stimulation (L-HFS), induces mossy fiber LTP presynaptically. To test whether or not calcium influx into CA3 pyramidal neurons is necessary for LTP induced by either pattern of stimulation, nimodipine, a L-type calcium channel antagonist, was added during stimulation. In these experiments nimodipine blocked the induction of mossy fiber LTP when B-HFS was given [34 ± 5% (mean ± SE) increase in control versus 7 ± 4% in nimodipine, P < 0.003]; in contrast, nimodipine did not block the induction of LTP with L-HFS (107 ± 10% in control vs. 80 ± 9% in nimodipine, P > 0.05). Administration of nimodipine after the induction of LTP had no effect on the expression of LTP. In addition, B- and L-HFS delivered directly to commissural/associational fibers in stratum radiatum failed to induce a N-methyl-d-aspartate-independent form of LTP, obviating the possibility that the presumed mossy fiber LTP resulted from potentiation of other synapses. Nimodipine had no effect on calcium transients recorded from mossy fiber presynaptic terminals evoked with the B-HFS paradigm but reduced postsynaptic calcium transients. Our results support the hypothesis that induction of mossy fiber LTP by B-HFS is mediated postsynaptically and requires entry of calcium through L-type channels into CA3 neurons.

scholarly journals Photolysis of Postsynaptic Caged Ca2+ Can Potentiate and Depress Mossy Fiber Synaptic Responses in Rat Hippocampal CA3 Pyramidal Neurons

2004 ◽  
Vol 91 (4) ◽  
pp. 1596-1607 ◽  
Author(s):  
Jun Wang ◽  
Mark F. Yeckel ◽  
Daniel Johnston ◽  
Robert S. Zucker
Keyword(s):  
Tyrosine Kinases ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Long Term Potentiation ◽  
Ca1 Neurons ◽  
Term Potentiation ◽  
Hippocampal Ca3 ◽  
Ca3 Pyramidal Neurons ◽  
Cell Somata

The induction of mossy fiber-CA3 long-term potentiation (LTP) and depression (LTD) has been variously described as being dependent on either pre- or postsynaptic factors. Some of the postsynaptic factors for LTP induction include ephrin-B receptor tyrosine kinases and a rise in postsynaptic Ca2+ ([Ca2+]i). Ca2+ is also believed to be involved in the induction of the various forms of LTD at this synapse. We used photolysis of caged Ca2+ compounds to test whether a postsynaptic rise in [Ca2+]i is sufficient to induce changes in synaptic transmission at mossy fiber synapses onto rat hippocampal CA3 pyramidal neurons. We were able to elevate postsynaptic [Ca2+]i to approximately 1 μm for a few seconds in pyramidal cell somata and dendrites. We estimate that CA3 pyramidal neurons have approximately fivefold greater endogenous Ca2+ buffer capacity than CA1 neurons, limiting the rise in [Ca2+]i achievable by photolysis. This [Ca2+]i rise induced either a potentiation or a depression at mossy fiber synapses in different preparations. Neither the potentiation nor the depression was accompanied by consistent changes in paired-pulse facilitation, suggesting that these forms of plasticity may be distinct from synaptically induced LTP and LTD at this synapse. Our results are consistent with a postsynaptic locus for the induction of at least some forms of synaptic plasticity at mossy fiber synapses.

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