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M Forti

Publications and source records attributed to M Forti.

11 recordsLinked to original sources
PubMed1999

Cellular mechanisms underlying spontaneous interictal spikes in an acute model of focal cortical epileptogenesis.

The cellular mechanisms involved in the generation of spontaneous epileptiform potentials were investigated in the pirifom cortex of the in vitro isolated guinea-pig brain. A single, unilateral injection of bicuculline (150-200 nmol) in the anterior piriform cortex induced locally spontaneous interictal spikes that recurred with a period of 8.81+/-4.47 s and propagated caudally to the ipsi- and contralateral hemispheres. Simultaneous extra- and intracellular recordings from layer II and III principal cells showed that the spontaneous interictal spike correlates to a burst of action potentials followed by a large afterdepolarization. Intracellular application of the sodium conductance blocker, QX-314 (80 mM), abolished bursting activity and unmasked a high-threshold slow spike enhanced by the calcium chelator EGTA (50 mM). The slow spike was abolished by membrane hyperpolarization and by local perfusion with 2 mM cadmium. The depolarizing potential that followed the primary burst was reduced by arterial perfusion with the N-methyl-D-aspartate receptor antagonist, DL-2-amino-5-phosphonopentanoic acid (100-200 microM). The non-N-methyl-D-aspartate glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM), completely and reversibly blocked the spontaneous spikes. The interictal spikes were terminated by a large afterpotential blocked either by intracellular QX-314 (80 mM) or by extracellular application of phaclofen and 2-hydroxysaclofen (10 and 4 mM, respectively). The present study demonstrates that, in an acute model of epileptogenesis, spontaneous interictal spikes are fostered by a primary burst of fast action potentials that ride on a regenerative high-threshold, possibly calcium-mediated spike, which activates a recurrent, glutamate-mediated potential responsible for the entrainment of adjacent and remote cortical regions. The bursting activity is controlled by a GABA(B) receptor-mediated inhibitory synaptic potential.

2-Amino-5-phosphonovalerate↗
PubMed1998

Synaptic connectivity of distinct hilar interneuron subpopulations.

Dual intracellular recordings of hilar interneurons and CA3 pyramidal cells were performed in transverse slices of guinea pig hippocampus in the presence of the convulsant compound 4-aminopyridine (4-AP) and ionotropic glutamate receptor antagonists. Under these conditions, interneurons burst fire synchronously, producing synchronized inhibitory postsynaptic potentials (sIPSPs) in pyramidal cells. Three different hilar interneuron subpopulations that contributed to the sIPSP were identified based on their projection properties and morphology. These three types were pyramidal-like stellate interneurons, spheroid interneurons, and oviform interneurons. Physiologically, pyramidal-like stellate interneurons could be differentiated from the other interneuron subpopulations because they generated short synchronized bursts of action potentials coincident with the hyperpolarizing and depolarizing gamma-aminobutyric acid-A (GABAA)-mediated inhibitory postsynaptic potentials (IPSPs) recorded in pyramidal cells. The bursts in pyramidal-like stellate cells were abolished by theGABAA-receptor blocker, bicuculline. In contrast, spheroid interneurons of the dentate-hilus (D-H) border and oviform hilar interneurons exhibited prolonged bicuculline-resistant bursts that occurred coincident with the GABAB pyramidal cell sIPSPs. Pyramidal-like stellate interneurons likely did not contribute to the generation of synchronized GABAB responses in hippocampal pyramidal cells. Spheroid interneurons were unique among these subpopulations of interneurons in that the bicuculline-resistant bursts in spheroid interneurons were sustained by a synaptic depolarization that persisted in the presence of antagonists of ionotropic glutamate, GABAA and GABAB receptors [6-cyano-7-nitroquinoxaline-2,3-dione, 20 microM; 3-3(2-carboxipiperazine-4-yl)propyl-1-phosphonate, 20 microM; bicuculline, 10-15 microM; CGP 55845A, 20 microM]. This novel depolarizing potential reversed between -30 and 0 mV. No noticeable synaptic depolarization sustaining burst firing could be isolated in oviform interneurons, suggesting that firing in this interneuron subpopulation was synchronized by nonsynaptic mechanisms. The results of the present study indicate that the hilar inhibitory circuit is composed of at least three different subpopulations of interneurons, distinguishable by their morphological characteristics and synaptic inputs and outputs. These findings give further support to the hypothesis that there are distinct populations of interneurons producing GABAA and GABAB responses with defined functional roles within the hippocampal inhibitory circuit. Notably, we found that spheroid interneurons were unique among the hilar interneurons studied, in that the synchronized bursts observed in these cells are sustained by a novel ionotropic glutamate and GABA receptor-independent synaptic depolarization.

4-Aminopyridine↗
PubMed1997

Novel glutamate- and GABA-independent synaptic depolarization in granule cells of guinea-pig hippocampus.

1. Dual intracellular recordings of granule cells, hilar interneurons and CA3 pyramidal cells were performed in transverse slices of guinea-pig hippocampus. At resting membrane potential, in the presence of 4-aminopyridine, ionotropic glutamate receptor antagonists and the GABAA receptor antagonist bicuculline, granule cells showed spontaneous, large amplitude depolarizations correlated with synchronous bursting activity of interneurons. 2. Under these conditions, pyramidal cells exhibited large amplitude monophasic GABAB inhibitory postsynaptic potentials (IPSPs) synchronous with the GABAergic interneuron burst discharges. The granule cells also received a GABAB input, which was evident only when the neurons were depolarized by DC injection. The GABAB receptor antagonist CGP 55,845A (CGP) blocked the GABAB IPSPs in both pyramidal cells and granule cells; however, the depolarizing potential in granule cells was unaffected by the drug. 3. The granule cells depolarization in the presence of CGP was monophasic and exhibited linear voltage dependence with a reversal potential around -40 mV, suggesting that it was generated by a synaptic input activating a mixed cationic current. 4. The granule cell depolarization was abolished following the addition of tetrodotoxin to the bath. In addition, perfusing the slice with a low Ca(2+)-containing solution (0.5 mM Ca(2+)-10 mM Mg2+) also abolished the granule cell depolarization, confirming the synaptic origin of the event. 5. (S)-Methyl-4-carboxyphenylglycine, L-(+)-2-amino-3-phosphonopropionic acid, propranolol and atropine did not affect the granule cell depolarization, indicating that metabotropic glutamate receptors, beta-adrenergic receptors and muscarinic cholinergic receptors were not involved in generating the granule cell depolarizing synaptic response. 6. These findings indicate that, in the absence of both glutamatergic and GABAergic inputs, synchronous interneuronal activity can produce a depolarizing synaptic response in granule cells. The neurochemical responsible for the depolarization is currently under investigation.

Animals↗
PubMed1997

Persistent excitability changes in the piriform cortex of the isolated guinea-pig brain after transient exposure to bicuculline.

The development of long-lasting excitability changes after a single intracerebral injection of bicuculline (1 mM) in a restricted region of the anterior piriform cortex was studied by means of simultaneous intra- and extracellular recordings in the isolated guinea-pig brain preparation maintained in vitro by arterial perfusion. The transitory disinhibition induced by bicuculline revealed transient afterdischarges that were followed by the activation of a synaptic potential mediated by the recurrent propagation of the focal epileptiform activity along cortico-cortical associative fibres. The epileptiform associative potential persisted for the duration of the experiment. Both the induction and the long-term expression of the epileptiform associative potential were dependent on the activation of glutamatergic receptors of the NMDA type, as demonstrated by perfusion with the NMDA receptor antagonist 2-aminopentanoic acid (AP5) (100 microM). After bicuculline washout, piriform cortex neurons responded to afferent stimulation with a burst discharge superimposed on a paroxysmal depolarizing potential. The early component of the burst was mediated by a Ca(2+)-dependent, non-synaptic potential located at the proximal apical dendrites and soma of layer II-III cells, since (i) it was abolished by membrane hyperpolarization, (ii) it was not affected by AP5, (iii) it was correlated with a current sink in layer II, as demonstrated by current source density analysis of field potential laminar profiles, and (iv) it was abolished by cadmium (2-5 mM) applied locally in layer II. The late component of the burst response (i) coincided in time with the extracellular epileptiform associative potential, (ii) increased linearly in amplitude during membrane hyperpolarization, (iii) was blocked by AP5, and (iv) was correlated with an extracellular sink in layer Ib, where the associative fibres contact the distal apical dendrites of piriform cortex neurons. The results presented here indicate that a transient focal disinhibition promotes persistent intrinsic and synaptic excitability changes in piriform cortex neurons. These changes may be responsible for the propagation of epileptiform activity and for the induction of secondary epileptogenesis.

Animals↗
PubMed1996

Propagation of epileptiform potentials in the guinea-pig piriform cortex is sustained by associative fibres.

The role of the associative connections in the propagation of epileptiform discharges originating from an acute, localized epileptic focus in the anterior piriform cortex has been characterized recently in the in vitro isolated guinea-pig brain preparation. The present study demonstrates that the dorsal propagation of epileptiform synaptic potentials generated in APC is carried by long-projective associative fibres. Current source density analysis of the field potential profiles evoked by stimulation of the lateral olfactory tract has been utilized to describe the functional circuit activated in rostral and caudal regions of the piriform cortex, before and after the induction of a bicuculline epileptic focus in the anterior piriform cortex. Separate stimulation of the lateral olfactory tract at two sites, caudal and rostral to a tract incision, activates epileptiform potentials that are generated at the site of primary focus in the anterior piriform cortex and travel along associative fibres. Selective cutting of the long-projective associative fibres abolishes the epileptic associative potential in the cortical regions caudal to the section. The present study demonstrates directly that epileptiform potentials propagate along associative fibres to cortical regions that are synaptically related to the focus of origin. Such a pattern of propagation may sustain the generation of secondary foci in cortical regions remote from the primary epileptic focus.

Animals↗
PubMed1996

Epileptiform activity in the piriform cortex of the in vitro isolated guinea pig brain preparation.

Brief intracerebral injections of bicuculline in the anterior portion of the piriform cortex of the isolated guinea pig brain preparation induce a transient, localized disinhibition confined to the site of drug application. The epileptiform activity generated at the bicuculline focus propagates and induces secondary excitability changes in remote cortical regions within the olfactory lobe. Long lasting changes in synaptic potentials were observed in the posterior piriform cortex, where long-projective cortico-cortical fibers originating from the site of bicuculline injection terminate. The activation of rhythmic, transient afterdischarges at the bicuculline focus was critical for the development of persistent 'epileptiform' associative synaptic potentials in remote cortical regions. When transient afterdischarges were prevented, epileptiform associative potentials in the posterior piriform cortex appeared only transiently and vanished within 20 min. The persistent secondary changes in synaptic excitability that occur in cortical regions distant from the acutely-induced primary epileptic focus may represent one of the transition mechanisms toward chronic epileptogenesis.

Animals↗
PubMed1994

Multifocal spontaneous epileptic activity induced by restricted bicuculline ejection in the piriform cortex of the isolated guinea pig brain.

1. We investigated the development of epileptic activity in the limbic lobe of the in vitro isolated brain preparation after induction of a restricted epileptic focus in the rostral portion of the anterior piriform cortex (APC) by means of local bicuculline ejection. 2. The modifications of the local responses evoked by stimulation of the lateral olfactory tract were consistent with an increase in excitability of layer II pyramidal neurons. The abnormal discharge output of the epileptic focus propagated throughout the piriform cortex (PC) and generated late synaptic stimulus-evoked epileptiform potentials in layer Ib, where corticocortical associative fibers contact the distal dendrites of pyramidal cells. 3. Spontaneous epileptiform potentials (SEPs) originated in the primary focus at the bicuculline ejection site 10-15 min after drug application and propagated via associative fibers to the posterior PC (PPC). 4. Autonomous secondary foci generating SEPs independently from the primary anterior focus developed in the PPC within 2 h after the bicuculline application. 5. Ictal events seldom occurred spontaneously in PC but could be induced by tetanic afferent stimulation. Evoked ictal events in PC had the characteristics of afterdischarges, being short in duration and localized in space and showing a progressively decreasing firing rate. 6. Self-sustained spontaneous ictal discharges were observed in the entorhinal cortex and hippocampus but not in PC after activation of the APC focus. 7. We conclude that in an acute pharmacological model of focal epilepsy, associative corticocortical connections hold a primary role 1) in the propagation of interictal epileptiform activity throughout the limbic lobe and 2) in the generation of secondary epileptic foci. We also demonstrate that self-sustained ictal events are not spontaneously generated in PC, although paroxysmal seizure-like discharges occur in hippocampus. We discuss the relevance of the rostral-to-caudal-directed associative fiber system in generation of limbic seizures.

Animals↗
PubMedDate not supplied

Optical coherence tomography (OCT) angiomatous prolifieration (RAP) in retinal.

PURPOSE: To verify the utility of optical coherence tomography (OCT) for diagnosing retinal angiomatous proliferations (RAP) in patients with exudative age-related macular degeneration (AMD). METHODS: Multiple cross-sections were taken with OCT from 41 eyes of 39 consecutive patients with AMD and RAP. The presence and the location of the angiomatous complexes had already been documented by fluorescein angiography (FA) and high-speed confocal indocyanine green videoangiography (ICGA). RESULTS: RAP was detectable by OCT scans in all 41 eyes, appearing as a focal hyper-reflecting area in the neuroretinal layers; it was frequently located close to the inner surface of the retinal pigment epithelium (29 eyes [70. 7%]). All eyes had either no or only a low-reflecting OCTsignal surrounding the RAP, caused by serous intraretinal edema. Only 13 eyes (31.7%), however, had large serous retinal detachment (SRD). OCT detected pigment epithelium detachment in 31 eyes (75.6%), but none had underlying choroidal neovascularization. CONCLUSIONS: OCT findings confirm the intraretinal localization of the RAP which are always associated with impressive exudative phenomena. OCT is therefore a useful diagnostic tool, adding information to FA and high-speed ICGA.

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