Prolonged field bursts in the dentate gyrus: dependence on low calcium, high potassium, and nonsynaptic mechanisms

1. The dentate gyrus has been proposed to be a gate for entry of neuronal activity into the hippocampus. This function would give it a critical role in the propagation of seizure activity in that region. The hallmark of epileptiform activity in the dentate itself, often referred to as "maximal dentate activation" (MDA), has not been reproduced previously in vitro. 2. With the use of rat hippocampal slices, bath [Ca2+] was decreased, and [K+] was increased concurrently to simulate conditions found during intense neuronal activity in vivo. Both evoked and spontaneous field bursts were observed in the dentate granule cell layer under these conditions. These bursts were similar to MDA, consisting of a prolonged negative shift in extracellular potential with large-amplitude population spikes. 3. In 0.5 mM bath [Ca2+], single stimuli applied to the perforant path could evoke prolonged field bursts in the dentate only when bath [K+] was > or = 9 mM. However, repetitive stimulation (10 Hz) of the perforant path could elicit similar dentate responses when bath [K+] was as low as 5 mM. 4. In 0.5 mM bath [Ca2+], interictal-type bursts appeared spontaneously in CA1 and CA3 when bath [K+] was > or = 5 mM but were lost when [K+] was > 9 mM. Spontaneous seizurelike activity in the dentate required a higher minimum bath [K+] (9 mM) and persisted at [K+] of 11 mM. 5. Stimulation-evoked field bursts in the dentate altered epileptiform activity in CA3. At bath [K+] insufficient to cause spontaneous CA3 bursts, CA3 was activated transiently when prolonged field bursts occurred in the dentate. At higher bath [K+] in which spontaneous CA3 bursts did occur, they were depressed during the dentate bursts. 6. Deletion of Ca2+ from the bath; the addition of 30 microM each of bicuculline methiodide, D,L-2-amino-5-phosphonopentanoate (AP-5), and 6,7-dinitroquinoxaline-2,3-dione (DNQX); or the combination of both manipulations did not block antidromically evoked or spontaneous prolonged field bursts in the dentate. Thus the mechanisms maintaining and propagating these events did not require fast amino acid-mediated synaptic transmission. 7. The concurrent alteration of [K+] and [Ca2+] required to produce prolonged field bursts in the dentate underscores the positive feedback relationship between neuronal excitation and extracellular ionic concentrations, whereas the ability of synaptic stimulation to trigger nonsynaptic seizurelike events such as these prolonged field bursts may be relevant to the transition from interictal to ictal activity in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

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Burst characteristics of dentate gyrus granule cells: evidence for endogenous and nonsynaptic properties

Journal of Neurophysiology ◽

10.1152/jn.1996.75.1.124 ◽

1996 ◽

Vol 75 (1) ◽

pp. 124-132 ◽

Cited By ~ 18

Author(s):

E. Pan ◽

J. L. Stringer

Keyword(s):

Dentate Gyrus ◽

Action Potentials ◽

Granule Cells ◽

Epileptiform Activity ◽

Hippocampal Slices ◽

Current Injection ◽

Single Action ◽

Epileptiform Discharges

1. Hippocampal slices bathed in 8 mM potassium and 0-added calcium exhibited spontaneous epileptiform activity in the dentate gyrus. Extracellular recording revealed recurrent prolonged bursts of population spikes and an associated negative DC shift. These episodes were very similar to the in vivo phenomenon termed maximal dentate activation (MDA). Therefore this in vitro activity will be referred to as MDA-like activity or events. 2. During the MDA-like activity, the individual granule cells exhibited a sustained depolarization that matched the duration of the negative extracellular DC shift. At the beginning of the MDA-like activity, there was a burst of action potentials. After the burst, most granule cells either continued to fire action potentials regularly or in bursts. Some cells exhibited this initial burst of activity and then a dramatic reduction in firing rate. This reduction in rate was followed by a gradual increase in the amplitude and frequency of the epileptiform activity recorded during the remainder of the MDA-like event. 3. Before and between MDA-like events, spontaneous cellular activity consisted of single action potentials and bursts of action potentials on a depolarizing envelope. In addition, depolarizing potentials, up to 13 mV, were recorded. There were no extracellular field potentials associated with these intracellularly recorded potentials. 4. In the 8 mM potassium, 0-added calcium test solution, the membrane potential threshold for burst production was significantly lower than in normal potassium and calcium medium. 5. The effect of depolarizing and hyperpolarizing current injections on the amplitude and frequency of the epileptiform activity was tested. Current injection had no effect on the frequency of the epileptiform activity recorded during the MDA-like events. However, the frequency of the cellular bursts between MDA-like events was very sensitive to current injection. Depolarizing current increased the frequency, and hyperpolarizing current decreased the frequency of the spontaneous activity. 6. This study has shown that in 8 mM potassium and 0-added calcium the granule cells of the dentate gyrus are capable of generating spontaneous bursts that appear to be mediated by endogenous mechanisms. In addition, synchronized epileptiform discharges were recorded from the granule cells at regular intervals that appear were recorded from the granule cells at regular intervals that appear to be mediated by exogenous nonsynaptic mechanisms.

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Recurrent Excitatory Connectivity in the Dentate Gyrus of Kindled and Kainic Acid–Treated Rats

Journal of Neurophysiology ◽

10.1152/jn.2000.83.2.693 ◽

2000 ◽

Vol 83 (2) ◽

pp. 693-704 ◽

Cited By ~ 96

Author(s):

Michael Lynch ◽

Thomas Sutula

Keyword(s):

Dentate Gyrus ◽

Kainic Acid ◽

Granule Cell ◽

Time Course ◽

Granule Cells ◽

Mossy Fiber ◽

Hippocampal Slices ◽

Granule Cell Layer ◽

Perforant Path ◽

Inhibitory Circuits

Repeated seizures induce mossy fiber axon sprouting, which reorganizes synaptic connectivity in the dentate gyrus. To examine the possibility that sprouted mossy fiber axons may form recurrent excitatory circuits, connectivity between granule cells in the dentate gyrus was examined in transverse hippocampal slices from normal rats and epileptic rats that experienced seizures induced by kindling and kainic acid. The experiments were designed to functionally assess seizure-induced development of recurrent circuitry by exploiting information available about the time course of seizure-induced synaptic reorganization in the kindling model and detailed anatomic characterization of sprouted fibers in the kainic acid model. When recurrent inhibitory circuits were blocked by the GABAAreceptor antagonist bicuculline, focal application of glutamate microdrops at locations in the granule cell layer remote from the recorded granule cell evoked trains of excitatory postsynaptic potentials (EPSPs) and population burst discharges in epileptic rats, which were never observed in slices from normal rats. The EPSPs and burst discharges were blocked by bath application of 1 μM tetrodotoxin and were therefore dependent on network-driven synaptic events. Excitatory connections were detected between blades of the dentate gyrus in hippocampal slices from rats that experienced kainic acid–induced status epilepticus. Trains of EPSPs and burst discharges were also evoked in granule cells from kindled rats obtained after ≥1 wk of kindled seizures, but were not evoked in slices examined 24 h after a single afterdischarge, before the development of sprouting. Excitatory connectivity between blades of the dentate gyrus was also assessed in slices deafferented by transection of the perforant path, and bathed in artificial cerebrospinal fluid (ACSF) containing bicuculline to block GABAA receptor–dependent recurrent inhibitory circuits and 10 mM [Ca2+]o to suppress polysynaptic activity. Low-intensity electrical stimulation of the infrapyramidal blade under these conditions failed to evoke a response in suprapyramidal granule cells from normal rats ( n = 15), but in slices from epileptic rats evoked an EPSP at a short latency (2.59 ± 0.36 ms) in 5 of 18 suprapyramidal granule cells. The results are consistent with formation of monosynaptic excitatory connections between blades of the dentate gyrus. Recurrent excitatory circuits developed in the dentate gyrus of epileptic rats in a time course that corresponded to the development of mossy fiber sprouting and demonstrated patterns of functional connectivity corresponding to anatomic features of the sprouted mossy fiber pathway.

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Role of Potassium and Calcium in the Generation of Cellular Bursts in the Dentate Gyrus

Journal of Neurophysiology ◽

10.1152/jn.1997.77.5.2293 ◽

1997 ◽

Vol 77 (5) ◽

pp. 2293-2299 ◽

Cited By ~ 20

Author(s):

Enhui Pan ◽

Janet L. Stringer

Keyword(s):

Dentate Gyrus ◽

Granule Cells ◽

Seizure Activity ◽

Epileptiform Activity ◽

Hippocampal Slices ◽

Extracellular Potassium ◽

Sprague Dawley

Pan, Enhui and Janet L. Stringer. Role of potassium and calcium in the generation of cellular bursts in the dentate gyrus. J. Neurophysiol. 77: 2293–2299, 1997. Epileptiform activity, which appears to be endogenous, has been recorded in the granule cells of the dentate gyrus before the onset of synchronized seizure activity and has been termed cellular bursts. It has been postulated that an increase in input to the dentate gyrus causes a local increase in extracellular K+ concentration ([K+]o) and a decrease in [Ca2+]o that results in this cellular bursting. The first test of this hypothesis is to determine whether the cellular bursts appear in ionic conditions that occur in vivo before the onset of synchronized epileptic activity. This hypothesis was tested in vitro by varying the ionic concentrations in the perfusing solution and recording changes in the granule cells of the dentate gyrus. Intra- and extracellular recordings were made in the dentate gyri of hippocampal slices prepared from anesthetized adult Sprague-Dawley rats. Increasing the extracellular potassium or decreasing the extracellular calcium of the perfusing solution caused three forms of spontaneous activity to appear: depolarizing potentials, action potentials, and cellular bursts. Increasing potassium or decreasing calcium also caused the granule cells to depolarize and reduced their input resistance. No synchronized extracellular field activity was detected. Simultaneously increasing potassium and decreasing calcium caused cellular bursts to appear at concentrations recorded in vivo before the onset of synchronized reverberatory seizure activity.

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Relationship between synaptic activity and prolonged field bursts in the dentate gyrus of the rat hippocampal slice

Journal of Neurophysiology ◽

10.1152/jn.1995.74.5.1947 ◽

1995 ◽

Vol 74 (5) ◽

pp. 1947-1952 ◽

Cited By ~ 11

Author(s):

J. S. Schweitzer ◽

A. Williamson

Keyword(s):

Synaptic Transmission ◽

Dentate Gyrus ◽

Granule Cell ◽

Hippocampal Slice ◽

Cell Layer ◽

Ion Concentration ◽

Granule Cell Layer ◽

Perforant Path ◽

Dentate Granule Cell ◽

Concentration Changes

1. Previous studies in the dentate granule cell layer of the rat hippocampal slice have demonstrated that nonsynaptic, seizurelike prolonged field bursts occur in conditions of low extracellular Ca2+ concentration ([Ca2+]o) and elevated [K+]o. We hypothesize that the extracellular ion concentration changes induced by synaptic activation of dentate granule cells would be sufficient to initiate these nonsynaptic bursts. 2. Using ion-selective electrode recording, we observed large changes in [Ca2+]o (from 1.3 mM baseline to approximately 0.7 mM) and [K+]o (from 3.5 to approximately 12 mM) in the dentate granule cell layer during repetitive electrical stimulation of the perforant path in rat hippocampal slices. Concomitant with these changes, bursts of population spikes similar to those seen during spontaneous prolonged field bursts appeared between the individual stimulus-evoked responses in the dentate gyrus in many of the slices studied (19 of 27). 3. Blockade of N-methyl-D-aspartate (NMDA), non-NMDA, and gamma-aminobutyric acid-A (GABAA)-mediated synaptic transmission during perforant path stimulation resulted in a marked reduction of the ion concentration changes and a loss of both stimulus-evoked and stimulus-independent population spikes in the dentate gyrus. 4. When slices were perfused with solutions containing [Ca2+]o and [K+]o equivalent to those measured during perforant path stimulation (i.e., 0.7 and 12 mM, respectively), spontaneous prolonged field bursts appeared in the dentate gyrus. Addition of NMDA, non-NMDA, and GABAA receptor antagonists did not prevent the occurrence of these spontaneous bursts. 5. We conclude that changes in [Ca2+]o and [K+]o sufficient to produce prolonged field bursts may be created in the dentate granule cell layer by perforant path stimulation. These effects are dependent on synaptic transmission. Once these ionic conditions occur, they are sufficient to trigger prolonged field bursts independent of fast amino-acid-mediated synaptic transmission. A similar mechanism could be important during the interictal-ictal transition in vivo.

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Electric field suppression of epileptiform activity in hippocampal slices

Journal of Neurophysiology ◽

10.1152/jn.1996.76.6.4202 ◽

1996 ◽

Vol 76 (6) ◽

pp. 4202-4205 ◽

Cited By ~ 119

Author(s):

B. J. Gluckman ◽

E. J. Neel ◽

T. I. Netoff ◽

W. L. Ditto ◽

M. L. Spano ◽

...

Keyword(s):

Electric Field ◽

Electric Fields ◽

Neuronal Activity ◽

Epileptiform Activity ◽

Hippocampal Slices ◽

Reference Electrode ◽

Recording Electrode ◽

Field Orientation ◽

Field Suppression

1. The effects of relatively small external DC electric fields on synchronous activity in CA1 and CA3 from transverse and longitudinal type hippocampal slices were studied. 2. To record neuronal activity during significant field changes, differential DC amplification was employed with a reference electrode aligned along an isopotential with the recording electrode. 3. Suppression of epileptiform activity was observed in 31 of 33 slices independent of region studied and type of slice but was highly dependent on field orientation with respect to the apical dendritic-somatic axis. 4. Modulation of neuronal activity in these experiments was readily observed at field strengths < or = 5–10 mV/mm. Suppression was seen with the field oriented (positive to negative potential) from the soma to the apical dentrites. 5. In vivo application of these results may be feasible.

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Spontaneous Waves in the Dentate Gyrus of Slices From the Ventral Hippocampus

Journal of Neurophysiology ◽

10.1152/jn.00478.2004 ◽

2004 ◽

Vol 92 (6) ◽

pp. 3385-3398 ◽

Cited By ~ 9

Author(s):

Laura Lee Colgin ◽

Don Kubota ◽

Fernando A. Brucher ◽

Yousheng Jia ◽

Erin Branyan ◽

...

Keyword(s):

Gap Junctions ◽

Dentate Gyrus ◽

Granule Cell ◽

Action Potentials ◽

Slow Wave Sleep ◽

Glutamate Release ◽

Acetylcholinesterase Inhibitor ◽

Granule Cell Layer ◽

Perforant Path ◽

The Waves

Spontaneous negative-going potentials occurring at an average frequency of 0.7 Hz were recorded from the dentate gyrus of slices prepared from the temporal hippocampus of young adult rats. These events (here termed “dentate waves”) in several respects resembled the dentate spikes described for freely moving rats during immobile behaviors and slow-wave sleep. Action potentials were observed on the descending portion of the in vitro waves and, as expected from this, whole cell recordings established that the waves were composed of depolarizing currents. Dentate waves appeared to be locally generated within the granule cell layer and were greatly reduced by antagonists of AMPA-type glutamate receptors or by lesions to the entorhinal cortex. Simultaneous recordings indicated that the waves were often synchronized in the inner and outer blades of the dentate gyrus. Knife cuts through the perforant path and the commissural/associational system did not eliminate synchronization, leaving electrotonic propagation via gap junctions as its probable cause. In accord with this, cuts that separated the two blades of the dentate eliminated synchronization between them, and a compound that inhibits gap junctions reduced wave activity. Dentate waves were regularly accompanied by sharp waves in field CA3 and were reduced in size by the acetylcholinesterase inhibitor, physostigmine. It is hypothesized that dentate waves occur when spontaneous glutamate release from dentate afferents produces action potentials in neighboring granule cells that then summate electrotonically into a population event; once initiated, the waves propagate, again electrotonically, and thereby engage a significant portion of the granule cell population.

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Astrocyte-secreted IL-33 mediates homeostatic synaptic plasticity in the adult hippocampus

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2020810118 ◽

2020 ◽

Vol 118 (1) ◽

pp. e2020810118

Author(s):

Ye Wang ◽

Wing-Yu Fu ◽

Kit Cheung ◽

Kwok-Wang Hung ◽

Congping Chen ◽

...

Keyword(s):

Synaptic Plasticity ◽

Neuronal Activity ◽

Hippocampal Slices ◽

Memory Formation ◽

Conditional Knockout ◽

Acute Administration ◽

Excitatory Synapses ◽

Homeostatic Synaptic Plasticity ◽

Hippocampal Ca1

Hippocampal synaptic plasticity is important for learning and memory formation. Homeostatic synaptic plasticity is a specific form of synaptic plasticity that is induced upon prolonged changes in neuronal activity to maintain network homeostasis. While astrocytes are important regulators of synaptic transmission and plasticity, it is largely unclear how they interact with neurons to regulate synaptic plasticity at the circuit level. Here, we show that neuronal activity blockade selectively increases the expression and secretion of IL-33 (interleukin-33) by astrocytes in the hippocampal cornu ammonis 1 (CA1) subregion. This IL-33 stimulates an increase in excitatory synapses and neurotransmission through the activation of neuronal IL-33 receptor complex and synaptic recruitment of the scaffold protein PSD-95. We found that acute administration of tetrodotoxin in hippocampal slices or inhibition of hippocampal CA1 excitatory neurons by optogenetic manipulation increases IL-33 expression in CA1 astrocytes. Furthermore, IL-33 administration in vivo promotes the formation of functional excitatory synapses in hippocampal CA1 neurons, whereas conditional knockout of IL-33 in CA1 astrocytes decreases the number of excitatory synapses therein. Importantly, blockade of IL-33 and its receptor signaling in vivo by intracerebroventricular administration of its decoy receptor inhibits homeostatic synaptic plasticity in CA1 pyramidal neurons and impairs spatial memory formation in mice. These results collectively reveal an important role of astrocytic IL-33 in mediating the negative-feedback signaling mechanism in homeostatic synaptic plasticity, providing insights into how astrocytes maintain hippocampal network homeostasis.

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