Effect of neonatal degranulation on the morphological development of rat CA3 pyramidal neurons: Inductive role of mossy fibers on the formation of thorny excrescences

1992 ◽  
Vol 321 (4) ◽  
pp. 612-625 ◽  
Author(s):  
J. L. Gaiarsa ◽  
M. Beaudoin ◽  
Y. Ben-Ari
Keyword(s):  
Pyramidal Neurons ◽  
Mossy Fibers ◽  
Morphological Development ◽  
Ca3 Pyramidal Neurons

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 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 Changes in Mint1, a Novel Synaptic Protein, After Transient Global Ischemia in Mouse Hippocampus

2000 ◽  
Vol 20 (10) ◽  
pp. 1437-1445 ◽  
Author(s):  
Hiroyuki Nishimura ◽  
Tomohiro Matsuyama ◽  
Kyoko Obata ◽  
Yatsuka Nakajima ◽  
Hideto Kitano ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Synaptic Vesicle ◽  
Entorhinal Cortex ◽  
Pyramidal Neurons ◽  
Mossy Fibers ◽  
Global Ischemia ◽  
Mouse Hippocampus ◽  
Ca3 Pyramidal Neurons ◽  
Neuronal Transmission ◽  
Transient Global Ischemia

Mints (munc18-interacting proteins) are novel multimodular adapter proteins in membrane transport and organization. Mint1, a neuronal isoform, is involved in synaptic vesicle exocytosis. Its potential effects on development of ischemic damage to neurons have not yet been evaluated. The authors examined changes in mint1 and other synaptic proteins by immunohistochemistry after transient global ischemia in mouse hippocampus. In sham-ischemic mice, immunoreactivity for mint1 was rich in fibers projecting from the entorhinal cortex to the hippocampus and in the mossy fibers linking the granule cells of the dentate gyrus to CA3 pyramidal neurons. Munc18-1, a binding partner of mint1, was distributed uniformly throughout the hippocampus, and synaptophysin 2, a synaptic vesicle protein, was localized mainly in mossy fibers. After transient global ischemia, mint1 immunoreactivity in mossy fibers was dramatically decreased at 1 day of reperfusion but actually showed enhancement at 3 days. However, munc18-1 and synaptophysin 2 were substantially expressed in the same region throughout the reperfusion period. These findings suggest that mint1 participates in neuronal transmission along the excitatory pathway linking the entorhinal cortex to CA3 in the hippocampus. Because mint1 was transiently decreased in the mossy fiber projection after ischemia, functional impairment of neuronal transmission in the projection from the dentate gyrus to CA3 pyramidal neurons might be involved in delayed neuronal death.

scholarly journals Activity-Dependent Release of Endogenous BDNF From Mossy Fibers Evokes a TRPC3 Current and Ca2+ Elevations in CA3 Pyramidal Neurons

2010 ◽  
Vol 103 (5) ◽  
pp. 2846-2856 ◽  
Author(s):  
Yong Li ◽  
Gaston Calfa ◽  
Takafumi Inoue ◽  
Michelle D. Amaral ◽  
Lucas Pozzo-Miller
Keyword(s):  
Transient Receptor Potential ◽  
Pyramidal Neurons ◽  
Mossy Fibers ◽  
Synaptic Function ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Ca3 Pyramidal Neurons ◽  
Activity Dependent ◽  
Theta Burst ◽  
Stimulation Of

Multiple studies have demonstrated that brain-derived neurotrophic factor (BDNF) is a potent modulator of neuronal structure and function in the hippocampus. However, the majority of studies to date have relied on the application of recombinant BDNF. We herein report that endogenous BDNF, released via theta burst stimulation of mossy fibers (MF), elicits a slowly developing cationic current and intracellular Ca2+ elevations in CA3 pyramidal neurons with the same pharmacological profile of the transient receptor potential canonical 3 (TRPC3)-mediated IBDNF activated in CA1 neurons by brief localized applications of recombinant BDNF. Indeed, sensitivity to both the extracellular BDNF scavenger tropomyosin-related kinase B (TrkB)-IgG and small hairpin interference RNA-mediated TRPC3 channel knockdown confirms the identity of this conductance as such, henceforth-denoted MF- IBDNF. Consistent with such activity-dependent release of BDNF, these MF- IBDNF responses were insensitive to manipulations of extracellular Zn2+ concentration. Brief theta burst stimulation of MFs induced a long-lasting depression in the amplitude of excitatory postsynaptic currents (EPSCs) mediated by both AMPA and N-methyl-d-aspartate (NMDA) receptors without changes in the NMDA receptor/AMPA receptor ratio, suggesting a reduction in neurotransmitter release. This depression of NMDAR-mediated EPSCs required activity-dependent release of endogenous BDNF from MFs and activation of Trk receptors, as it was sensitive to the extracellular BDNF scavenger TrkB-IgG and the tyrosine kinase inhibitor k-252b. These results uncovered the most immediate response to endogenously released—native—BDNF in hippocampal neurons and lend further credence to the relevance of BDNF signaling for synaptic function in the hippocampus.

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 Loss of Calretinin in L5a impairs the formation of the barrel cortex leading to abnormal whisker-mediated behaviors

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Mingzhao Su ◽  
Junhua Liu ◽  
Baocong Yu ◽  
Kaixing Zhou ◽  
Congli Sun ◽  
...  
Keyword(s):  
Information Integration ◽  
Pyramidal Neurons ◽  
Barrel Cortex ◽  
Sensory Information ◽  
Membrane Excitability ◽  
Novelty Preference ◽  
Layer 4 ◽  
Dendritic Complexity ◽  
Cortex System

AbstractThe rodent whisker-barrel cortex system has been established as an ideal model for studying sensory information integration. The barrel cortex consists of barrel and septa columns that receive information input from the lemniscal and paralemniscal pathways, respectively. Layer 5a is involved in both barrel and septa circuits and play a key role in information integration. However, the role of layer 5a in the development of the barrel cortex remains unclear. Previously, we found that calretinin is dynamically expressed in layer 5a. In this study, we analyzed calretinin KO mice and found that the dendritic complexity and length of layer 5a pyramidal neurons were significantly decreased after calretinin ablation. The membrane excitability and excitatory synaptic transmission of layer 5a neurons were increased. Consequently, the organization of the barrels was impaired. Moreover, layer 4 spiny stellate cells were not able to properly gather, leading to abnormal formation of barrel walls as the ratio of barrel/septum size obviously decreased. Calretinin KO mice exhibited deficits in exploratory and whisker-associated tactile behaviors as well as social novelty preference. Our study expands our knowledge of layer 5a pyramidal neurons in the formation of barrel walls and deepens the understanding of the development of the whisker-barrel cortex system.

Dopamine Increases the Gain of the Input-Output Response of Rat Prefrontal Pyramidal Neurons

2008 ◽  
Vol 99 (6) ◽  
pp. 2985-2997 ◽  
Author(s):  
Kay Thurley ◽  
Walter Senn ◽  
Hans-Rudolf Lüscher
Keyword(s):  
Working Memory ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
D1 Receptors ◽  
Input Output ◽  
Prefrontal Cortical ◽  
Noisy Input ◽  
Relationship Of

Dopaminergic modulation of prefrontal cortical activity is known to affect cognitive functions like working memory. Little consensus on the role of dopamine modulation has been achieved, however, in part because quantities directly relating to the neuronal substrate of working memory are difficult to measure. Here we show that dopamine increases the gain of the frequency-current relationship of layer 5 pyramidal neurons in vitro in response to noisy input currents. The gain increase could be attributed to a reduction of the slow afterhyperpolarization by dopamine. Dopamine also increases neuronal excitability by shifting the input-output functions to lower inputs. The modulation of these response properties is mainly mediated by D1 receptors. Integrate-and-fire neurons were fitted to the experimentally recorded input-output functions and recurrently connected in a model network. The gain increase induced by dopamine application facilitated and stabilized persistent activity in this network. The results support the hypothesis that catecholamines increase the neuronal gain and suggest that dopamine improves working memory via gain modulation.

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