Immature Status Epilepticus Alters the Temporal Relationship between Hippocampal Interictal Epileptiform Discharges and High-frequency Oscillations.

The aim was to investigate the long-term effects of a single episode of immature Status Epilepticus (SE) on the excitability of the septal and temporal hippocampus in vitro, by studying the relationship between interictal-like epileptiform discharges (IEDs) and high-frequency oscillations (HFOs; Ripples, Rs and Fast Ripples, FRs). A pentylenetetrazol-induced Status Epilepticus-(SE)-like generalized seizure was induced at postnatal day 20 in 22 male and female juvenile rats, sacrificed >40 days later to prepare hippocampal slices. Spontaneous IEDs induced by Mg-free ACSF were recorded from the CA3 area of temporal (T) or septal (S) slices.

Timing differences between HFOs and interictal epileptiform discharges generated in vitro by different mechanisms in rat hippocampal slices: A novel approach.

Objective: To investigate the effect of generating mechanism on the relationship between interictal-like epileptiform discharges (IEDs) and the underlying High Frequency Oscillations (HFOs; Ripples, R, and Fast Ripples, FR).

Methods: Synchronous spontaneous IEDs were recorded from the CA1 area of hippocampal slices from adult rats, perfused by Mg -free ACSF (n = 41slices/14 animals) or 4-aminopyridine (50 μM, n = 37slices/16 animals); IED filtering revealed Rs and FRs and several metrics were calculated and compared (amplitude, duration, relative onset, time lag, % overlap, peak frequency, peak power, FR/R).

Results: Longer IEDs and higher 1st Population Spike (PS) amplitude in Mg -free ACSF (vs 4-AP; P < .

Prenatal alcohol exposure affects developmental differentiation of interictal discharges in septal and temporal hippocampus.

Prenatal alcohol exposure (PAE) provokes lifelong CNS dysfunction, including an increased susceptibility to seizure disorders. We investigated hippocampal excitability in the offspring of dams exposed to a mild ethanol concentration throughout pregnancy (ethanol 15%v/v in drinking water). Hippocampal slices were prepared from the offspring at a young (Y, 21-30 postnatal days, PND) or adult (A, 60 PND) age, with controls from same age normal rats (N).

Region-specific Effects of Early-life Status Epilepticus on the Adult Hippocampal CA3 - Medial Entorhinal Cortex Circuitry In vitro: Focus on Interictal Spikes and Concurrent High-frequency Oscillations.

Convulsive status epilepticus (SE) in immature life is often associated with lasting neurobiological changes. We provoked SE by pentylenetetrazole in postnatal day 20 rat pups and examined communication modalities between the temporal hippocampus and medial entorhinal cortex (mEC) in vitro. After a minimum of 40 days post-SE, we prepared combined temporal hippocampal - medial entorhinal cortex (mEC) slices from conditioned (SE) and naïve (N) adult rats and recorded 4-aminopyridine-induced spontaneous epileptiform interictal-like discharges (IED) simultaneously from CA3 and mEC layer V-VI.

Immature Status Epilepticus: In Vitro Models Reveal Differences in Cholinergic Control and HFO Properties of Adult CA3 Interictal Discharges in Temporal vs Septal Hippocampus.

We have earlier demonstrated that a Status Epilepticus (SE) during CNS development has long-lasting effects on cholinergic neurotransmission, detectable in vitro and in vivo. In this work, we aimed to localize changes in temporal (T) vs septal (S) hippocampus and to correlate adult CA3 interictal epileptiform discharge (IED) frequency changes to those of Ripples (R) and Fast Ripples (FR) of the High-Frequency Oscillations (HFOs). Spontaneous IEDs were induced by bathing slices in Mg-free ACSF or in 4-Aminopyridine (4-AP, 50 µM) and data were analyzed separately for each model.

A single episode of juvenile status epilepticus reduces the threshold to adult seizures in a stimulus-specific way.

We have previously reported that an episode of pentylenetetrazole (PTZ)-induced status epilepticus (SE) in immature rats induces a long-term increase in cholinergic excitation assessed in the adult brain in vitro. In this in vivo work, we tested the responsiveness of adult SE-conditioned rats to pilocarpine and PTZ, two convulsants with different mechanisms of action. Postnatal day (P) 20 Sprague-Dawley juvenile rats were conditioned by an episode of PTZ-induced SE (i.

Endogenous ACh effects on NMDA-induced interictal-like discharges along the septotemporal hippocampal axis of adult rats and their modulation by an early life generalized seizure.

Purpose:   Our earlier findings of the modulation of cholinergic neurotransmission by an early life generalized seizure and the reported interaction between muscarinic and N-methyl-d-aspartate (NMDA) receptors prompted us to investigate the effects of endogenous acetylcholine (ACh) on the frequency (Hz) of the epileptiform discharges following NMDA-receptor activation in the hippocampal slice.

Methods:   A sustained (>20 min) generalized convulsion was induced in Sprague-Dawley juvenile rats by intraperitoneal injection with pentylenetetrazole (PTZ, 70-90 mg/kg) at postnatal day (P) 20. Temporal and septal hippocampal slices were prepared of normal (N) and PTZ-treated (PTZ) adult (≥P60) rats, and CA3 field potentials were recorded during perfusion with Mg(2+) -free artificial cerebrospinal fluid (ACSF) or with ACSF containing 50 μm 4-aminopyridine (4-AP).

Febrile seizures in the predisposed brain: a new model of temporal lobe epilepsy.

The atypical febrile seizure has important clinical implications because of its association with the mesial temporal lobe epilepsy syndrome, which is the most common of the intractable epilepsies. However, whether a causal relation exists between these conditions is currently unknown. We have previously shown that a focal cortical lesion induced in the neonatal rat predisposes to the development of atypical hyperthermic seizures.

A pentylenetetrazole-induced generalized seizure in early life enhances the efficacy of muscarinic receptor coupling to G-protein in hippocampus and neocortex of adult rat.

We have previously shown that exposure to the anti-cholinesterase eserine provokes interictal-like discharges in the CA3 area of hippocampal slices from adult rats in which a generalized seizure has been induced by pentylenetetrazole (PTZ) when immature (at 20 days). Such increased responsiveness to acetylcholine (ACh) was not associated with any change in hippocampal acetylcholine or gamma-aminobutyric acid (GABA) content, GABAergic inhibition or density of ACh innervation, but was blocked by the muscarinic receptor antagonist atropine. We therefore turned to quantitative radioligand binding autoradiography, in situ hybridization and the [35S]GTPgammaS method to assess the properties of hippocampal and neocortical muscarinic receptors in adult rats having experienced a PTZ seizure at P20.

The A3 adenosine receptor agonist 2-Cl-IB-MECA facilitates epileptiform discharges in the CA3 area of immature rat hippocampal slices.

The effects of the A(3) adenosine receptor agonist 2-Cl-IB-MECA were tested on epileptiform field potentials recorded in the CA3 area of postnatal days 10-20 immature hippocampal slices, during perfusion with the GABA(A) receptor antagonist bicuculline (10 microM). Evoked potentials: 2-Cl-IB-MECA (1-50 microM, n = 17) had consistently excitatory effects, blocked by the A(3) receptor antagonist MRS 1220 (1 microM, n = 7), but not occluded in the presence of the A(1) antagonist DPCPX (1 microM, n = 12) or the A(2A) antagonist ZM-241385 (0.1 microM, n = 12).

Freeze lesion-induced focal cortical dysplasia predisposes to atypical hyperthermic seizures in the immature rat.

Purpose: To determine the effects of focal cortical dysplasia on the behavioral and electrographic features of hyperthermia-induced seizures (HSs) in rats.

Methods: A right sensorimotor cortex freeze lesion was induced in postnatal day 1 (P1) rat pups, and HSs were provoked at P10 under continuous monitoring of core temperature; EEGs were recorded from the right amygdala during and after hyperthermia. Controls included both sham-operated at P1 and naïve rats.

Modulation of muscarinic facilitation of epileptiform discharges in immature rat neocortex.

We examined the cholinergic effects on epileptiform discharge generation in immature (postnatal days 10-20) rat neocortex. Evoked and spontaneous field potentials were recorded from the deep layers of neocortical slices during GABA(A) receptor blockade by bicuculline methiodide (BMI, 50 microM). The anticholinesterase eserine (10 microM) as well as the ACh-analog carbamylcholine chloride (CCh, 25 microM) decreased the amplitude and duration of evoked field potentials and in parallel, increased significantly the rate of occurrence of spontaneous discharges.

Nicotinic effects on excitatory field potentials recorded from the immature CA3 area of rat hippocampal slices.

We investigated the nicotinic modulation of the excitatory field potentials recorded from the immature (postnatal day 10-20) hippocampal CA3 area, in the presence of the GABA(A) antagonist bicuculline methiodide (BMI, 10 microM). Nicotine (50 microM) enhanced the evoked field potentials; its effects were also observed in the presence of the GABA(B) antagonist 2-hydroxy-saclofen (250 microM; added to BMI) and were blocked by pre-perfusion with the nicotinic antagonist hexamethonium (HXM, 50 microM). The potentiating effects of nicotine in BMI persisted during prolonged perfusion (more than 20 min), while those in control perfusion medium were transient.

Pentylenetetrazol-induced seizures in immature rats provoke long-term changes in adult hippocampal cholinergic excitability.

Purpose: We previously demonstrated that the anticholinesterase eserine provokes interictal-like discharges in the CA3 area of hippocampal slices from rats in which generalized seizures had been induced by pentylenetetrazol (PTZ) when immature. In this study, we investigated several factors as the possible mechanism for this effect, including age at convulsions.

Methods: Rats were injected with PTZ on postnatal day (P) 18-20 or >P60, and neuronal activity was recorded intra- and extracellularly from CA3 5-10 or >40 days later.

AIDA, a class I metabotropic glutamate-receptor antagonist limits kainate-induced hippocampal dysfunction.

Purpose: In the developing animal, intraperitoneal injections of kainic acid (KA) lead to a prolonged initial seizure followed by chronic recurrent seizures and long-term hippocampal dysfunction. We investigated whether the class I metabotropic glutamate receptor (mGluR) antagonist 1-aminoindan-1,5-dicarboxylic acid (AIDA) is neuroprotective in the KA model of epilepsy.

Methods: Immature rats aged postnatal day 20 (P20) and P30 were injected with fixed volumes of KA, KA + AIDA, AIDA, or saline.