Burst generation in neocortical neurons after GABA withdrawal in the rat

Abstract

1. gamma-Aminobutyric acid (GABA) withdrawal syndrome (GWS) represents a particular model of focal epilepsy consecutive to the interruption of a chronic intracortical GABA infusion and is characterized by the appearance of focal epileptic electroencephalographic (EEG) discharges and localized clinical signs on withdrawal of GABA. Effects of Ca2+ channel blockers and N-methyl-D-aspartate (NMDA) antagonists were evaluated in living rats presenting a GWS after interruption of a 5-day GABA infusion into the somatomotor cortex and in neocortical slices obtained from such rats. Bursting properties and morphology of neurons were also analyzed in slices. 2. In living rats, the noncompetitive NMDA antagonist phencyclidine [1-(1-phenylcyclohexyl)piperidine] and the Ca2+ antagonist flunarizine [E-1 (bis(4fluorophenyl)methyl)-4(3phenyl2-propenyl)-piperazine] were administered systemically to two groups of rats. Rats in the first group (n = 12) were injected with the drug 30-60 min before discontinuation of the GABA infusion. In this case, phencyclidine (10 mg/kg ip) prevented the development of GWS (n = 5), whereas flunarizine (40 mg/kg ip) had no consistent effect on the GWS appearance and characteristics (n = 7). Rats in the second group (n = 12) were injected 60-90 min after GABA discontinuation, i.e., during a fully developed GWS. In that case, neither drug suppressed GWS. 3. Neuronal activities in the epileptic focus were studied in slices with conventional intracellular recording and stimulation techniques. From the 65 neurons recorded, 29 responded with EPSPs and paroxysmal depolarization shifts (PDSs) to white matter stimulation (synaptic bursting or SB cells). Nineteen other neurons presented, in addition to synaptically induced PDSs, bursts of action potentials (APs) induced by intracellular depolarizing current injection (intrinsic bursting or IB cells). The remaining 17 neurons presented no bursting properties to either synaptic stimulation or depolarizing current injection (nonbursting or NB cells). 4. The recorded neurons were located 0.7-1.2 mm distant from the lesion because of the penetration of the GABA infusion cannula. Intracellular injection of neurons (n = 4) with biocytin or Lucifer yellow revealed that both SB and IB neurons were large, spiny pyramidal neurons localized in layer V of the sensorimotor cortex. 5. Bath application of the selective antagonist of NMDA receptors DL-2amino-5phosphonovalerate or DL-2amino-7phosphonoheptanoate (10-50 microM) reversibly reduced the amplitude (by 25-50%) and the duration (by 20-25%) of PDSs in all cases (n = 17).(ABSTRACT TRUNCATED AT 400 WORDS)

Age dependency of trauma-induced neocortical epileptogenesis

“…Paroxysmal activity emerges upon withdrawal from chronic GABA infusion (Brailowsky et al, 1988, 1989; Silva-Barrat et al, 1992). The hyperpolarization induced by GABA infusion is consistent with the hypothesis that reduced activity or periodic silence in some cortical territories for days, weeks, or months favor the occurrence of seizures.…”

Gamma Oscillation Maintains Stimulus Structure-Dependent Synchronization in Cat Visual Cortex

“…However, most intracellular studies clearly find an intrinsic afterhyperpolarization (AHP) after bursts that would produce the refractory period (Agmon and Connors 1989;Brumberg et al 2000;Connors and Gutnick 1990;Frenceschetti et al 1995;Gray and McCormick 1996;Nowak et al 2003;Silva-Barrat et al 1992;Traub and Miles 1991).…”

“…Stimulus-dependent gamma oscillation is found in the membrane potential of hyperpolarized cells (Jagadeesh et al 1992), but because hyperpolarization of one cell does not disable the network, that does not rule out a role for feedback in the oscillation. Bursting also requires a suprathreshold potential (Agmon and Connors 1989;Brumberg et al 2000;Connors and Gutnick 1990;Frenceschetti et al 1995;Gray and McCormick 1996;Nowak et al 2003;Silva-Barrat et al 1992;Traub and Miles 1991), suggesting that synchronous inputs encourage both bursts and oscillation. Bursts and GABAergic networks might even be viewed as coincident detectors (Galarreta and Hestrin 2001; Harris et al 2001).…”

Injury Induced Epileptogenesis: Contribution of Active Inhibition, Disfacilitation and Deafferentation to Seizure Induction in Thalamocortical System

“…(2) Similarly to undercut, chronic GABA infusion suppresses activity in the region of infusion and upon withdrawal from chronic GABA, paroxysmal activities occur (Brailowsky et al 1988(Brailowsky et al , 1989Silva-Barrat et al 1992). (3) Neocortical kindling is most efficient when electrical stimulation is applied during transition from SWS to waking state, suggesting that the presence of silent network states may be favorable in the development of epilepsy (Nita et al 2008a, b).…”