Desynchronization of Glutamate Release Prolongs Synchronous CA3 Network Activity

2007 ◽  
Vol 97 (5) ◽  
pp. 3812-3818 ◽  
Author(s):  
Jethro Jones ◽  
Elizabeth A. Stubblefield ◽  
Timothy A. Benke ◽  
Kevin J. Staley
Keyword(s):  
Glutamate Release ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Network Activity ◽  
Neural Population ◽  
Axon Terminals ◽  
Rate Of Spread ◽  
Hippocampal Ca3 ◽  
Recurrent Collateral

Periodic bursts of activity in the disinhibited in vitro hippocampal CA3 network spread through the neural population by the glutamatergic recurrent collateral axons that link CA3 pyramidal cells. It was previously proposed that these bursts of activity are terminated by exhaustion of releasable glutamate at the recurrent collateral synapses so that the next periodic burst of network activity cannot occur until the supply of glutamate has been replenished. As a test of this hypothesis, the rate of glutamate release at CA3 axon terminals was reduced by substitution of extracellular Ca2+ with Sr2+. Reduction of the rate of glutamate release reduces the rate of depletion and should thereby prolong bursts. Here we demonstrate that Sr2+ substitution prolongs spontaneous bursts in the disinhibited adult CA3 hippocampal slices to 37.2 ± 7.6 (SE) times the duration in control conditions. Sr2+ also decreased the probability of burst initiation and the rate of burst onset, consistent with reduced synchrony of glutamate release and a consequent reduced rate of spread of excitation through the slice. These findings support the supply of releasable glutamate as an important determinant of the probability and duration of synchronous CA3 network activity.

Statistical Model Relating CA3 Burst Probability to Recovery From Burst-Induced Depression at Recurrent Collateral Synapses

2001 ◽  
Vol 86 (6) ◽  
pp. 2736-2747 ◽  
Author(s):  
Kevin J. Staley ◽  
Jaideep S. Bains ◽  
Audrey Yee ◽  
Jennifer Hellier ◽  
J. Mark Longacher
Keyword(s):  
Time Constant ◽  
Neuronal Excitability ◽  
Pyramidal Cells ◽  
Network Activity ◽  
Interval Change ◽  
Epileptiform Discharges ◽  
Recurrent Collateral ◽  
Pace Maker

When neuronal excitability is increased in area CA3 of the hippocampus in vitro, the pyramidal cells generate periodic bursts of action potentials that are synchronized across the network. We have previously provided evidence that synaptic depression at the excitatory recurrent collateral synapses in the CA3 network terminates each population burst so that the next burst cannot begin until these synapses have recovered. These findings raise the possibility that burst timing can be described in terms of the probability of recovery of this population of synapses. Here we demonstrate that when neuronal excitability is changed in the CA3 network, the mean and variance of the interburst interval change in a manner that is consistent with a timing mechanism comprised of a pool of exponentially relaxing pacemakers. The relaxation time constant of these pacemakers is the same as the time constant describing the recovery from activity-dependent depression of recurrent collateral synapses. Recovery was estimated from the rate of spontaneous transmitter release versus time elapsed since the last CA3 burst. Pharmacological and long-term alterations of synaptic strength and network excitability affected CA3 burst timing as predicted by the cumulative binomial distribution if the burst pace-maker consists of a pool of recovering recurrent synapses. These findings indicate that the recovery of a pool of synapses from burst-induced depression is a sufficient explanation for burst timing in the in vitro CA3 neuronal network. These findings also demonstrate how information regarding the nature of a pacemaker can be derived from the temporal pattern of synchronous network activity. This information could also be extracted from less accessible networks such as those generating interictal epileptiform discharges in vivo.

Calcium-dependent current generating the afterhyperpolarization of hippocampal neurons

1986 ◽  
Vol 55 (6) ◽  
pp. 1268-1282 ◽  
Author(s):  
B. Lancaster ◽  
P. R. Adams
Keyword(s):  
Voltage Clamp ◽  
Hippocampal Neurons ◽  
Hippocampal Slices ◽  
Outward Current ◽  
Pyramidal Cells ◽  
Resting Potential ◽  
Tail Current ◽  
Calcium Dependent ◽  
K Current

A single-electrode voltage-clamp technique was employed on in vitro hippocampal slices to examine the membrane current responsible for the slow afterhyperpolarization (AHP) in CA1 pyramidal cells. This was achieved by using conventional procedures to evoke an AHP in current clamp, followed rapidly by a switch into voltage clamp (hybrid clamp). The AHP current showed a dependence on extracellular K+, which was close to that predicted for a K+ current by the Nernst equation. The AHP current could be blocked by Cd2+ or norepinephrine. Although the AHP current showed a requirement for voltage-dependent Ca2+ entry, the current did not show any clear intrinsic voltage dependence. Once activated, AHP current is not turned off by hyperpolarizing the membrane potential. The effects of norepinephrine, Cd2+, and tetraethylammonium (TEA) were used to identify an AHP current component to the outward current evoked by depolarizing voltage commands from holding potentials that approximate to the resting potential for these cells. The AHP current can contribute significantly to the outward current during the depolarizing command. Upon repolarization it is evident as a slow outward tail current. This slow tail current had the same time constant as AHP currents evoked by hybrid clamp. Fast components to the tail currents were also observed. These were sensitive to Cd2+ and TEA. They probably represent a voltage-sensitive gKCa, sometimes termed C-current. The strong sensitivity to voltage and TEA displayed by the conventionally described gKCa (IC) are properties inconsistent with the AHP. It seems likely that the AHP current (IAHP) represents a Ca2+-activated K+ current separate from IC and that these two currents coexist in the same cell.

The dendritic origins of penicillin-induced epileptogenesis in CA3 hippocampal pyramidal cells

1986 ◽  
Vol 56 (6) ◽  
pp. 1718-1738 ◽  
Author(s):  
J. W. Swann ◽  
R. J. Brady ◽  
R. J. Friedman ◽  
E. J. Smith
Keyword(s):  
Cell Body ◽  
Average Distance ◽  
Hippocampal Slices ◽  
Current Source ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Large Current ◽  
Hippocampal Ca3 ◽  
Ca3 Pyramidal Cells ◽  
Negative Field

Experiments were performed in order to identify the sites of epileptiform burst generation in rat hippocampal CA3 pyramidal cells. A subsequent slow field potential was studied, which is associated with afterdischarge generation. Laminar field potential and current source-density (CSD) methods were employed in hippocampal slices exposed to penicillin. Simultaneous intracellular and extracellular field recordings from the CA3 pyramidal cell body layer showed that whenever an epileptiform burst was recorded extracellularly, individual CA3 neurons underwent an intense depolarization shift. In extracellular records a slow negative field potential invariably followed epileptiform burst generation. In approximately 10% of slices, synchronous afterdischarges rode on the envelope of this negative field potential. Intracellularly a depolarizing afterpotential followed the depolarization shift and was coincident with the extracellular slow negative field potential. A one-dimensional CSD analysis performed perpendicular to the CA3 cell body layer showed that during epileptiform burst generation large current sinks occur simultaneously in the central portions of both the apical and basilar dendrites. The average distance of the peak amplitude for these sinks from the center of the cell body layer was 175 +/- 46.8 microns and 158 +/- 25.0 microns, respectively. A large current source was recorded in the cell body layer. Smaller current sources were observed in the distal portions of the dendritic layers. During the postburst slow field potential a current sink was recorded at the edge of the cell body layer in stratum oriens--a region referred to as the infrapyramidal zone. Simultaneous with the current sink recorded there, smaller sinks were often observed in the dendritic layers that appeared to be "tails" or prolongations of the currents underlying burst generation. Two-dimensional analyses of these field potentials were performed on planes parallel and perpendicular to the exposed surface of the slice. Isopotential contours showed that the direction of extracellular current is mainly orthogonal to the CA3 laminae. Correction of CSD estimates made perpendicular to the cell body layer for current flowing in the other direction did not alter the location of computed current sources and sinks. In order to show that the dendritic currents associated with epileptiform burst generation were active sinks, tetrodotoxin (TTX) was applied locally to the dendrites where the current sinks were recorded.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Ginkgo Extract EGb761 Confers Neuroprotection by Reduction of Glutamate Release in Ischemic Brain

2012 ◽  
Vol 15 (1) ◽  
pp. 94 ◽  
Author(s):  
Alexander Mdzinarishvili ◽  
Rachita K. Sambria ◽  
Dorothee Lang ◽  
Jochen Klein
Keyword(s):  
Glutamate Release ◽  
Hippocampal Slices ◽  
Brain Slices ◽  
Cell Swelling ◽  
Experimental Stroke ◽  
Cell Degeneration ◽  
Edema Formation ◽  
Ginkgo Extract

Purpose - Ginkgo extract EGb761 has shown anti-edema and anti-ischemic effects in various experimental models. In the present study, we demonstrate neuroprotective effects of EGb761 in experimental stroke while monitoring brain metabolism by microdialysis. Methods - We have used oxygen-glucose deprivation in brain slices in vitro and middle cerebral artery occlusion (MCAO) in vivo to induce ischemia in mouse brain. We used microdialysis in mouse striatum to monitor extracellular concentrations of glucose and glutamate. Results - In vitro, EGb761 reduced ischemia-induced cell swelling in hippocampal slices by 60%. In vivo, administration of EGb761 (300 mg/kg) reduced cell degeneration and edema formation after MCAO by 35-50%. Immediately following MCAO, striatal glucose levels dropped to 25% of controls, and this reduction was not significantly affected by EGb761. Striatal glutamate levels, in contrast, increased 15-fold after MCAO; after pretreatment with EGb761, glutamate levels only increased by 4-5fold. Conclusions - We show that pretreatment with EGb761 strongly reduces cellular edema formation and neurodegeneration under conditions of ischemia. The mechanism of action seems to be related to a reduction of excitotoxicity, because ischemia-induced release of glutamate was strongly suppressed. Ginkgo extracts such as EGb761 may be valuable to prevent ischemia-induced damage in stroke-prone patients. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Spike Timing of Lacunosom-Moleculare Targeting Interneurons and CA3 Pyramidal Cells During High-Frequency Network Oscillations In Vitro

2007 ◽  
Vol 98 (1) ◽  
pp. 96-104 ◽  
Author(s):  
Jay Spampanato ◽  
Istvan Mody
Keyword(s):  
High Frequency ◽  
Epileptiform Activity ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Spike Timing ◽  
Network Activity ◽  
Network Oscillations ◽  
Ca3 Pyramidal Cells

Network activity in the 200- to 600-Hz range termed high-frequency oscillations (HFOs) has been detected in epileptic tissue from both humans and rodents and may underlie the mechanism of epileptogenesis in experimental rodent models. Slower network oscillations including theta and gamma oscillations as well as ripples are generated by the complex spike timing and interactions between interneurons and pyramidal cells of the hippocampus. We determined the activity of CA3 pyramidal cells, stratum oriens lacunosum-moleculare (O-LM) and s. radiatum lacunosum-moleculare (R-LM) interneurons during HFO in the in vitro low-Mg2+ model of epileptiform activity in GIN mice. In these animals, interneurons can be identified prior to cell-attached recordings by the expression of green-fluorescent protein (GFP). Simultaneous local field potential recordings from s. pyramidale and on-cell recordings of individual interneurons and principal cells revealed three primary firing behaviors of the active cells: 36% of O-LM interneurons and 60% of pyramidal cells fired action potentials at high frequencies during the HFO. R-LM interneurons were biphasic in that they fired at high frequency at the beginning of the HFO but stopped firing before its end. When considering only the highest frequency component of the oscillations most pyramidal cells fired on the rising phase of the oscillation. These data provide evidence for functional distinction during HFOs within otherwise homogeneous groups of O-LM interneurons and pyramidal cells.

scholarly journals Presynaptic cholinergic neuromodulation alters the temporal dynamics of short-term depression at parvalbumin-positive basket cell synapses from juvenile CA1 mouse hippocampus

2015 ◽  
Vol 113 (7) ◽  
pp. 2408-2419 ◽  
Author(s):  
J. Josh Lawrence ◽  
Heikki Haario ◽  
Emily F. Stone
Keyword(s):  
Pyramidal Cell ◽  
Acetylcholine Receptors ◽  
Temporal Dynamics ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Calcium Transient ◽  
Muscarinic Acetylcholine Receptors ◽  
Presynaptic Calcium

Parvalbumin-positive basket cells (PV BCs) of the CA1 hippocampus are active participants in theta (5–12 Hz) and gamma (20–80 Hz) oscillations in vivo. When PV BCs are driven at these frequencies in vitro, inhibitory postsynaptic currents (IPSCs) in synaptically connected CA1 pyramidal cells exhibit paired-pulse depression (PPD) and multiple-pulse depression (MPD). Moreover, PV BCs express presynaptic muscarinic acetylcholine receptors (mAChRs) that may be activated by synaptically released acetylcholine during learning behaviors in vivo. Using acute hippocampal slices from the CA1 hippocampus of juvenile PV-GFP mice, we performed whole cell recordings from synaptically connected PV BC-CA1 pyramidal cell pairs to investigate how bath application of 10 μM muscarine impacts PPD and MPD at CA1 PV BC-pyramidal cell synapses. In accordance with previous studies, PPD and MPD magnitude increased with stimulation frequency. mAChR activation reduced IPSC amplitude and transiently reduced PPD, but MPD was largely maintained. Consistent with a reduction in release probability ( pr), MPD and mAChR activation increased both the coefficient of variation of IPSC amplitudes and the fraction of failures. Using variance-mean analysis, we converted MPD trains to pr functions and developed a kinetic model that optimally fit six distinct pr conditions. The model revealed that vesicular depletion caused MPD and that recovery from depression was dependent on calcium. mAChR activation reduced the presynaptic calcium transient fourfold and initial pr twofold, thereby reducing PPD. However, mAChR activation slowed calcium-dependent recovery from depression during sustained repetitive activity, thereby preserving MPD. Thus the activation of presynaptic mAChRs optimally protects PV BCs from vesicular depletion during short bursts of high-frequency activity.

scholarly journals Regional heterogeneity of developing GABAergic interneuron excitation in vivo

2019 ◽  
Author(s):  
Yasunobu Murata ◽  
Matthew T. Colonnese
Keyword(s):  
Synapse Formation ◽  
Critical Role ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Gabaergic Neurons ◽  
Network Activity ◽  
Gabaergic Interneuron ◽  
Intact Brain

AbstractGABAergic interneurons are proposed to be critical for early activity and synapse formation by directly exciting, rather than inhibiting, neurons in developing hippocampus and neocortex. However, the role of GABAergic neurons in the generation of neonatal network activity has not been tested in vivo, and recent studies have challenged the excitatory nature of early GABA. By locally manipulating interneuron activity in unanesthetized neonatal mice, we show that GABAergic neurons are indeed excitatory in hippocampus at postnatal-day 3 (P3), and responsible for most of the spontaneous firing of pyramidal cells at that age. Hippocampal interneurons become inhibitory by P7, whereas cortical interneurons are inhibitory at P3 and remain so throughout development. This regional and age heterogeneity is the result of a change in chloride reversal potential as activation of light-gated anion channels expressed in glutamatergic neurons causes firing in hippocampus at P3, but silences it at P7. This study in the intact brain reveals a critical role for GABAergic interneuron excitation in neonatal hippocampus, and a surprising heterogeneity of interneuron function in cortical circuits that was not predicted from in vitro studies.

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