Transient mossy fiber collaterals during the postnatal period when the mossy fibers form syanpses with CA3 pyramidal cells

The application of tetraethylammonium (TEA), a blocker of voltage-dependent potassium channels, can induce long-term potentiation (LTP) in the synaptic systems CA3–CA1 and mossy fiber-CA3 pyramidal cells of the hippocampus. In the mossy fibers, the depolarization evoked by extracellular TEA induces a large amount of glutamate and also of zinc release. It is considered that zinc has a neuromodulatory role at the mossy fiber synapses, which can, at least in part, be due to the activation of presynaptic ATP-dependent potassium (KATP) channels. The aim of this work was to study properties of TEA-induced zinc signals, detected at the mossy fiber region, using the permeant form of the zinc indicator Newport Green. The application of TEA caused a depression of those signals that was partially blocked by the KATP channel inhibitor tolbutamide. After the removal of TEA, the signals usually increased to a level above baseline. These results are in agreement with the idea that intense zinc release during strong synaptic events triggers a negative feedback action. The zinc depression, caused by the LTP-evoking chemical stimulation, turns into potentiation after TEA washout, suggesting the existence of a correspondence between the observed zinc potentiation and TEA-evoked mossy fiber LTP.

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Recruitment of an inhibitory hippocampal network after bursting in a single granule cell

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0702164104 ◽

2007 ◽

Vol 104 (18) ◽

pp. 7640-7645 ◽

Cited By ~ 27

Author(s):

Masahiro Mori ◽

Beat H. Gähwiler ◽

Urs Gerber

Keyword(s):

Pyramidal Cell ◽

Granule Cell ◽

Mossy Fiber ◽

Mossy Fibers ◽

Pyramidal Cells ◽

Network Activity ◽

Inhibitory Input ◽

Inhibitory Interneurons ◽

Failure Rates ◽

Ca3 Pyramidal Cells

The hippocampal CA3 area, an associational network implicated in memory function, receives monosynaptic excitatory as well as disynaptic inhibitory input through the mossy-fiber axons of the dentate granule cells. Synapses made by mossy fibers exhibit low release probability, resulting in high failure rates at resting discharge frequencies of 0.1 Hz. In recordings from functionally connected pairs of neurons, burst firing of a granule cell increased the probability of glutamate release onto both CA3 pyramidal cells and inhibitory interneurons, such that subsequent low-frequency stimulation evoked biphasic excitatory/inhibitory responses in a CA3 pyramidal cell, an effect lasting for minutes. Analysis of the unitary connections in the circuit revealed that granule cell bursting caused powerful activation of an inhibitory network, thereby transiently suppressing excitatory input to CA3 pyramidal cells. This phenomenon reflects the high incidence of spike-to-spike transmission at granule cell to interneuron synapses, the numerically much greater targeting by mossy fibers of inhibitory interneurons versus principal cells, and the extensively divergent output of interneurons targeting CA3 pyramidal cells. Thus, mossy-fiber input to CA3 pyramidal cells appears to function in three distinct modes: a resting mode, in which synaptic transmission is ineffectual because of high failure rates; a bursting mode, in which excitation predominates; and a postbursting mode, in which inhibitory input to the CA3 pyramidal cells is greatly enhanced. A mechanism allowing the transient recruitment of inhibitory input may be important for controlling network activity in the highly interconnected CA3 pyramidal cell region.

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Origin of the Apparent Asynchronous Activity of Hippocampal Mossy Fibers

Journal of Neurophysiology ◽

10.1152/jn.1997.78.1.24 ◽

1997 ◽

Vol 78 (1) ◽

pp. 24-30 ◽

Cited By ~ 12

Author(s):

Darrell A. Henze ◽

Nathaniel N. Urban ◽

German Barrionuevo

Keyword(s):

Mossy Fiber ◽

Molecular Layer ◽

Mossy Fibers ◽

Pyramidal Cells ◽

Antidromic Activation ◽

Stratum Lucidum ◽

Hippocampal Area ◽

Ca3 Pyramidal Cells ◽

Area Ca3

Henze, Darrell A., Nathaniel N. Urban, and German Barrionuevo. Origin of the apparent asynchronous activity of hippocampal mossy fibers. J. Neurophysiol. 78: 24–30, 1997. Fiber volleys (FVs) from the stratum lucidum of rat hippocampal area CA3 were recorded extracellularly from in vitro slices in the presence of 10 mM kynurenic acid. In agreement with previous work, bulk stimulation of the dentate gyrus (DG) near the hilar border leads to an asynchronous FV. Transection of the stratum lucidum between the DG stimulation site and the CA3 recording site reduced or eliminated the early components of the asynchronous FV, indicating that they are of mossy fiber (MF) origin. In contrast, moving the stimulating electrode away from the hilus toward the hippocampal fissure reduced or eliminated the late components of the FV. Subsequently, we found that bulk stimulation on the DG/hilar border induces an antidromic population spike in CA3 pyramidal cells. Finally, the MFs and associational collaterals have differentconduction velocities (0.51 and 0.37 m/s, respectively; temperature =33°C). From these data, we conclude that the late components of the asynchronous FV are due to antidromic activation of CA3 collaterals that have been shown to be present in the DG and hilus. A corollary of these findings is that bulk stimulation on the DG/hilar border can lead to at least two different monosynaptic inputs to CA3 pyramidal cells: the MFs and the antidromically activated associational collaterals. We suggest that when MF synaptic responses are being evoked with the use of bulk stimulation, stimulating electrodes should be placed in the outer molecular layer of the DG to prevent the activation of hilar-projecting associational collaterals. This procedure should be added to the previously proposed criteria for preventing polysynaptic contamination of the intracellularly recorded evoked MF synaptic response.

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

10.1101/158444 ◽

2017 ◽

Cited By ~ 1

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.

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Postsynaptic hyperpolarization increases the strength of AMPA-mediated synaptic transmission at large synapses between mossy fibers and CA3 pyramidal cells

Neuropharmacology ◽

10.1016/s0028-3908(00)00076-9 ◽

2000 ◽

Vol 39 (12) ◽

pp. 2288-2301 ◽

Cited By ~ 14

Author(s):

Nicola Berretta ◽

Aleksej V Rossokhin ◽

Alexander M Kasyanov ◽

Maxim V Sokolov ◽

Enrico Cherubini ◽

...

Keyword(s):

Synaptic Transmission ◽

Mossy Fibers ◽

Pyramidal Cells ◽

Ca3 Pyramidal Cells

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Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits

PLoS Computational Biology ◽

10.1371/journal.pcbi.1009435 ◽

2021 ◽

Vol 17 (10) ◽

pp. e1009435

Author(s):

Luke Y. Prince ◽

Travis Bacon ◽

Rachel Humphries ◽

Krasimira Tsaneva-Atanasova ◽

Claudia Clopath ◽

...

Keyword(s):

Granule Cells ◽

Mossy Fiber ◽

Pyramidal Cells ◽

Recurrent Network ◽

Memory Storage ◽

Neuronal Ensembles ◽

Hippocampal Ca3 ◽

Ca3 Pyramidal Cells ◽

Episodic Memories ◽

Mossy Fiber Pathway

In the hippocampus, episodic memories are thought to be encoded by the formation of ensembles of synaptically coupled CA3 pyramidal cells driven by sparse but powerful mossy fiber inputs from dentate gyrus granule cells. The neuromodulators acetylcholine and noradrenaline are separately proposed as saliency signals that dictate memory encoding but it is not known if they represent distinct signals with separate mechanisms. Here, we show experimentally that acetylcholine, and to a lesser extent noradrenaline, suppress feed-forward inhibition and enhance Excitatory–Inhibitory ratio in the mossy fiber pathway but CA3 recurrent network properties are only altered by acetylcholine. We explore the implications of these findings on CA3 ensemble formation using a hierarchy of models. In reconstructions of CA3 pyramidal cells, mossy fiber pathway disinhibition facilitates postsynaptic dendritic depolarization known to be required for synaptic plasticity at CA3-CA3 recurrent synapses. We further show in a spiking neural network model of CA3 how acetylcholine-specific network alterations can drive rapid overlapping ensemble formation. Thus, through these distinct sets of mechanisms, acetylcholine and noradrenaline facilitate the formation of neuronal ensembles in CA3 that encode salient episodic memories in the hippocampus but acetylcholine selectively enhances the density of memory storage.

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Localization of Brain-Derived Neurotrophic Factor to Distinct Terminals of Mossy Fiber Axons Implies Regulation of Both Excitation and Feedforward Inhibition of CA3 Pyramidal Cells

Journal of Neuroscience ◽

10.1523/jneurosci.3846-04.2004 ◽

2004 ◽

Vol 24 (50) ◽

pp. 11346-11355 ◽

Cited By ~ 62

Author(s):

S. C. Danzer

Keyword(s):

Neurotrophic Factor ◽

Mossy Fiber ◽

Pyramidal Cells ◽

Brain Derived Neurotrophic Factor ◽

Ca3 Pyramidal Cells ◽

Feedforward Inhibition

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Acetylcholine disinhibits hippocampal circuits to enable rapid formation of overlapping memory ensembles

10.1101/201699 ◽

2017 ◽

Author(s):

Luke Y. Prince ◽

Krasimira Tsaneva-Atanasova ◽

Claudia Clopath ◽

Jack R. Mellor

Keyword(s):

Granule Cells ◽

Mossy Fiber ◽

Pyramidal Cells ◽

Cholinergic Receptor ◽

Receptor Activation ◽

Cellular Excitability ◽

Rapid Formation ◽

Ca3 Pyramidal Cells ◽

Episodic Memories ◽

Spiking Neural Network Model

AbstractIn the hippocampus, episodic memories are thought to be encoded by the formation of ensembles of synaptically coupled CA3 pyramidal cells driven by sparse but powerful mossy fiber inputs from dentate gyrus granule cells. Acetylcholine is proposed as the salient signal that determines which memories are encoded but its actions on mossy fiber transmission are largely unknown. Here, we show experimentally that cholinergic receptor activation suppresses feedforward inhibition and enhances excitatory-inhibitory ratio. In reconstructions of CA3 pyramidal cells, this disinhibition enables postsynaptic dendritic depolarization required for synaptic plasticity at CA3-CA3 recurrent synapses. We further show in a spiking neural network model of CA3 how a combination of disinhibited mossy fiber activity, enhanced cellular excitability and reduced recurrent synapse strength can drive rapid overlapping ensemble formation. Thus, we propose a coordinated set of mechanisms by which acetylcholine release enables the selective encoding of salient high-density episodic memories in the hippocampus.

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Characteristics of local excitatory circuits studied with glutamate microapplication in the CA3 area of rat hippocampal slices

Journal of Neurophysiology ◽

10.1152/jn.1988.59.1.90 ◽

1988 ◽

Vol 59 (1) ◽

pp. 90-109 ◽

Cited By ~ 64

Author(s):

E. P. Christian ◽

F. E. Dudek

Keyword(s):

Granule Cells ◽

Mossy Fiber ◽

Hippocampal Slices ◽

Pyramidal Cells ◽

Firing Frequency ◽

Block Transmission ◽

Inhibitory Circuits ◽

Axon Terminals ◽

Stratum Pyramidale ◽

Ca3 Pyramidal Cells

1. Local neuronal circuits in CA3 of hippocampal slices were studied by recording excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) intracellularly during glutamate microapplication in CA3. Control experiments validated this approach by providing evidence that glutamate microdrops stimulated neurons but not axons-of-passage or axon terminals in CA3. 2. Glutamate microdrops (10-20 mM, 10-20 microns diam) increased the firing frequency of extracellularly recorded dentate granule cells for 5–10 s when applied to their somata but not when applied to their mossy fiber axons and terminals in the hilus and in CA3. 3. Glutamate microapplications to granule cell somata, but not to mossy fiber axons, also increased the frequency of intracellularly recorded EPSPs in CA3 pyramidal cells for 5-10 s. This provided a second line of evidence that glutamate did not cause firing in mossy fiber axons synapsing in CA3. 4. In slices where the CA3 region was surgically separated from the dentate gyrus and CA2, glutamate microdrops placed in the CA3 stratum pyramidale within 400 microns of intracellularly recorded pyramidal cells increased the frequency of EPSPs and IPSPs. Tetrodotoxin (1 microgram/ml) blocked these increases in PSP frequency, indicating that they did not result from glutamate-induced depolarization and associated transmitter release from presynaptic terminals. Increases in PSP frequency were interpreted to reflect glutamate activations of CA3 neurons with local synaptic connections to recorded cells. 5. Low concentrations of picrotoxin (PTX, 5-10 microM) blocked glutamate-induced increases in IPSP frequency and often revealed increases in EPSP frequency where they were not previously observed. This suggests that recurrent inhibitory circuits normally mask or block transmission through recurrent excitatory pathways in CA3. 6. In five experiments following PTX treatment (7.5–10 microM), large and prolonged (up to 2 min) increases in EPSP frequency were observed in CA3 pyramidal cells to glutamate microapplications in CA3. Rhythmic epileptiform bursts eventually occurred in two of these cases, suggesting that the protracted increases in EPSP frequency represent a form of reverberating excitation during a transition from normal to epileptic states. 7. Sixteen CA3 pyramidal cells were recorded in PTX (5-10 microM) during glutamate microapplications at 200 and 400 microns on each side of the recording site. The most consistent glutamate-induced increases in EPSP frequency occurred to microapplications 200 microns from recording sites on the hilar side.(ABSTRACT TRUNCATED AT 400 WORDS)

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