The synaptic nature of the paroxysmal depolarizing shift in hippocampal neurons

Johnston, Daniel; Brown, Thomas H.

doi:10.1002/ana.410160711

Cited by 75 publications

(30 citation statements)

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“…(Figure 1d) and intracellular electrodes were filled with the lidocaine analog QX314 (200 mM in 1M potassium acetate; Alomone Labs) to block action potentials in a subset of recordings (n = 3 cells). The results confirmed that a “giant EPSP” occurred during epileptiform discharges of the area CA3 network (Figure 1d), similar to previous descriptions of bursts recorded from disinhibited slices of normal rats (Johnston & Brown, 1984). …”

Section: Resultssupporting

confidence: 90%

“…The results are consistent with the recent finding by Ellender and colleagues (2010) that CA3 pyramidal cells are highly likely to participate in epileptiform bursts. Hyperpolarization of CA3 neurons did not prevent epileptiform bursts, suggesting that they were mediated by “giant” EPSPs, which is also similar to previous reports of area CA3 burst discharges in normal rats after disinhibition or convulsant treatment (Johnston & Brown, 1984). …”

Section: Discussionsupporting

confidence: 90%

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Progressive, potassium-sensitive epileptiform activity in hippocampal area CA3 of pilocarpine-treated rats with recurrent seizures

McCloskey

Scharfman

2011

Epilepsy Research

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Rat hippocampal area CA3 pyramidal cells synchronously discharge in rhythmic bursts of action potentials after acute disinhibition or convulsant treatment in vitro. These burst discharges resemble epileptiform activity, and are of interest because they may shed light on mechanisms underlying limbic seizures. However, few studies have examined CA3 burst discharges in an animal model of epilepsy, because a period of prolonged, severe seizures (status epilepticus) is often used to induce the epileptic state, which can lead to extensive neuronal loss in CA3. Therefore, the severity of pilocarpine-induced status epilepticus was decreased with anticonvulsant treatment to reduce damage. Rhythmic burst discharges were recorded in the majority of slices from these animals, between two weeks and nine months after status epilepticus. The incidence and amplitude of bursts progressively increased with time after status, even after spontaneous behavioral seizures had begun. The results suggest that modifying the pilocarpine models of temporal lobe epilepsy to reduce neuronal loss leads to robust network synchronization in area CA3. The finding that these bursts increase long after spontaneous behavioral seizures begin supports previous arguments that temporal lobe epilepsy exhibits progressive pathophysiology.

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Section: Resultssupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Progressive, potassium-sensitive epileptiform activity in hippocampal area CA3 of pilocarpine-treated rats with recurrent seizures

McCloskey

Scharfman

2011

Epilepsy Research

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“…The paroxysmal depolarizing shift is a manifestation of neural epilepsy that is in contrast to endogenous burst firing as it is network driven (Johnston and Brown, 1984). In some neurons, V m did not return to baseline and seizure-like activities persisted.…”

Section: Discussionmentioning

confidence: 95%

Stellate and pyramidal neurons in goldfish telencephalon respond differently to anoxia and GABA receptor inhibition

Hossein-Javaheri¹,

Wilkie²,

Lado

et al. 2016

Journal of Experimental Biology

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With oxygen deprivation, the mammalian brain undergoes hyperactivity and neuronal death while this does not occur in the anoxiatolerant goldfish (Carassius auratus). Anoxic survival of the goldfish may rely on neuromodulatory mechanisms to suppress neuronal hyper-excitability. As γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, we decided to investigate its potential role in suppressing the electrical activity of goldfish telencephalic neurons. Utilizing whole-cell patch-clamp recording, we recorded the electrical activities of both excitatory ( pyramidal) and inhibitory (stellate) neurons. With anoxia, membrane potential (V m ) depolarized in both cell types from −72.2 mV to −57.7 mV and from −64.5 mV to −46.8 mV in pyramidal and stellate neurons, respectively. While pyramidal cells remained mostly quiescent, action potential frequency (AP f ) of the stellate neurons increased 68-fold. Furthermore, the GABA A receptor reversal potential (E GABA ) was determined using the gramicidin perforated-patch-clamp method and found to be depolarizing in pyramidal (−53.8 mV) and stellate neurons (−42.1 mV). Although GABA was depolarizing, pyramidal neurons remained quiescent as E GABA was below the action potential threshold (−36 mV pyramidal and −38 mV stellate neurons). Inhibition of GABA A receptors with gabazine reversed the anoxiamediated response. While GABA B receptor inhibition alone did not affect the anoxic response, co-antagonism of GABA A and GABA B receptors (gabazine and CGP-55848) led to the generation of seizure-like activities in both neuron types. We conclude that with anoxia, V m depolarizes towards E GABA which increases AP f in stellate neurons and decreases AP f in pyramidal neurons, and that GABA plays an important role in the anoxia tolerance of goldfish brain.

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“…Current flowing directly through glutamate-receptor channels probably also contribute to the PDS as well (Johnston and Brown 1984), possibly via the newly described dendritic NMDA spikes (Schiller et al 2000). However, active dendritic conductances contribute Ն10 -20 mV to the peak amplitude of the PDS, as this constitutes the difference between the peak voltage value of PDS responses and the reversal potential of ionotropic glutamate-receptor channels.…”

Section: Inter-ictal-like Pds Responsesmentioning

confidence: 99%

Inter-Ictal- and Ictal-Like Epileptic Discharges in the Dendritic Tree of Neocortical Pyramidal Neurons

Schiller

2002

Journal of Neurophysiology

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Schiller, Yitzhak. Inter-ictal-and ictal-like epileptic discharges in the dendritic tree of neocortical pyramidal neurons. J Neurophysiol 88: 2954 -2962, 2002; 10.1152/jn.00525.2001. Dendritic mechanisms have been implied to play a key role in the formation of epileptic discharges. However, presently only a handful of direct dendritic recordings have been reported during epileptic discharges. In this study, I performed simultaneous voltage recordings from the soma and apical dendrite of the same neuron combined with calciumimaging measurements to investigate inter-ictal-and ictal-like epileptic discharges in dendrites of layer 5 pyramidal neurons. Neocortical brain slices treated with bicuculline (BCC) produced both isolated "inter-ictal" paroxysymal depolarization shift (PDS) responses and electrographic seizures. Concomitant voltage recordings from the soma and apical dendrite revealed that PDS responses developed in both the apical dendrites and soma. However, the two responses differed from one another. In apical dendrites, the PDS was significantly higher in amplitude and shorter in duration compared with the somatic PDS. The PDS response in dendrites had a peak amplitude of 68.9 Ϯ 2.2 (SD) mV, peak voltage value of 9.3 Ϯ 2.7 mV, and half-width of 203.8 Ϯ 38.4 ms. In contrast, the somatic PDS had a peak amplitude of 48.7 Ϯ 2.7 mV, peak voltage value of Ϫ11.9 Ϯ 3.1 mV, and half-width of 247.8 Ϯ 57.3 ms (P Ͻ 0.01, n ϭ 18). In addition the apical dendritic PDS always preceded the somatic counterpart in all 18 neurons examined. Concomitant calcium-imaging measurements showed the PDS evoked large calcium influx into the entire dendritic tree including the apical tuft, basal, and oblique dendrites. The PDS evoked [Ca 2ϩ ] i were not uniform along the dendritic tree, being highest in the oblique dendrites (71.3 Ϯ 14.5 M) and lowest at the distal tuft branches (9.3 Ϯ 0.7 M). The PDS responses persisted after blockade of voltage-gated sodium channels by intracellular QX-314 but became narrower (by 69.6 Ϯ 9.7%) following intracellular administration of the voltage-gated calcium channel blocker D600. Electrographic seizures recorded in the soma and apical dendrites were composed of recurrent bursts. The initial bursts represented PDS responses. During the seizure the amplitude of bursts gradually attenuated and reached an average value of 26 Ϯ 13% of the initial ictal PDS burst. Double recordings during electrographic seizures revealed the initial one to four ictal bursts appeared first at the apical dendrite while later ictal bursts were always observed first at the soma. In conclusion, the results of this study show "inter-ictal" PDS responses originated in the apical dendritic tree, were partially mediated by voltage-gated calcium channels and spread throughout the dendritic tree including the fine tuft, basal, and oblique dendrites. During electrographic seizures the origin of epileptic bursts shifted from the apical dendritic tree to the soma-basal region.

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The synaptic nature of the paroxysmal depolarizing shift in hippocampal neurons

Cited by 75 publications

References 50 publications

Progressive, potassium-sensitive epileptiform activity in hippocampal area CA3 of pilocarpine-treated rats with recurrent seizures

Progressive, potassium-sensitive epileptiform activity in hippocampal area CA3 of pilocarpine-treated rats with recurrent seizures

Stellate and pyramidal neurons in goldfish telencephalon respond differently to anoxia and GABA receptor inhibition

Inter-Ictal- and Ictal-Like Epileptic Discharges in the Dendritic Tree of Neocortical Pyramidal Neurons

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