Maternal hyperhomocysteinemia increases seizures susceptibility of neonatal rats.

AIMS: Neonatal seizures are severe pathologies which may result in long-term neurological consequences. High plasma concentrations of homocysteine - hyperhomocysteinemia (hHCy) - are associated with epilepsy. In the present study, we evaluated susceptibility to seizure of neonatal rats with prenatal hHCy. MAIN METHODS: Prenatal hHCy was induced by feeding females with a high-methionine diet. Experiments were performed on pups during the first three postnatal weeks. Flurothyl-induced epileptic behavior was assessed according to Racine's scale. Epileptiform activity in the hippocampus was recorded using electrophysiological methods. The balance of excitation/inhibition, functional GABAergic inhibition and GABA reversal potential in hippocampal neurons were analyzed. KEY FINDINGS: Rats with hHCy developed more severe stages of behavioral patterns during flurothyl-induced epilepsy with shorter latency. Electrophysiological recordings demonstrated higher background neuronal activity in rats with hHCy. Seizure-like events triggered by flurothyl (in vivo) or 4-aminopyridine (in vitro) showed shorter latency, higher power and amplitude. An increased glutamate/GABA synaptic ratio was shown in the pyramidal neurons of rats with hHCy and more slices demonstrated excitation by isoguvacine, a selective GABA(A) receptor agonist, during the first and second postnatal weeks. The GABA driving force and the reversal potential of GABA(A) currents were more positive during the second postnatal week for hHCy rats. SIGNIFICANCE: The higher susceptibility to seizures in rats with prenatal hHCy due to a shift in the balance of excitation/inhibition toward excitation may underlie the clinical evidence about the association of hHCy with an increased risk of epilepsy.

[Comparative analysis of safety of carotid endarterectomy performed in acutest and acute periods of ischaemic stroke]. / Sravnitel'nyi analiz bezopasnosti vypolneniia karotidnoi éndarteréktomii v ostreishii i ostryi periody ishemicheskogo insul'ta.

Surgical revascularization of the carotid basin in the acutest period of ischaemic stroke, i.e., within 72 hours, will make it possible to prevent the development of recurrent stroke by removing an embologenically dangerous atherosclerotic plaque of the symptomatic carotid artery and to improve cerebral blood supply, having eliminated haemodynamic stenosis of the carotid artery. However, the problem of safety of carotid endarterectomy in patients during the acutest period of ischaemic stroke still remains debatable. PURPOSE: To comparatively analyse safety of eversion carotid endarterectomy performed in the acutest (0-72 hours) and acute (4-14 days) periods of minor ischaemic stroke. PATIENTS AND METHODS: Between January 2015 and December 2019, specialists of the Department of Vascular Surgery of Municipal Clinical Hospital # 7 of Kazan performed a total of 80 eversion carotid reconstructions in the period of minor ischaemic stroke within 14 days. The patients were divided into 2 groups depending on the terms of performing carotid endarterectomy. The first group comprised 32 (40.0%) patients operated on in the acutest period of ischaemic stroke, i.e., within 72 hours from the onset of first symptoms of neurological deficit. The second group included 48 (60.0%) patients subjected to carotid endarterectomy within 4 to 14 days from the onset of first signs of neurological deficit. RESULTS: According to the obtained findings, haemorrhagic transformation in the early postoperative period occured in 2 Group Two patients, with one lethal outcome on POD 3. Cerebral ischaemia increased in one patient of each group without enlargement of the ischaemic zone according to brain computed tomography, with residual neurological deficit in Group I in remote period (Rankin scale score 1) and complete restoration in Group II (Rankin scale score 0). Recurrent minor ischaemic stroke on POD 1 developed in Group II with formation of a new lacunar region of ischaemia of the brain in the operated carotid basin and was verified by the findings of cerebral MRI with persisting neurological deficit for 6 months (Rankin scale score 2). The comparative assessment of severity of stroke on the day of operation and at discharge, as well as that of neurological symptomatology during the 1st and 6th months of follow up in both groups proved positive. No events of acute coronary syndrome, recurrent strokes or lethal outcomes were observed during the follow-up period. CONCLUSION: According to the findings of our study, patients with acute cerebral circulation impairment caused by embologenically dangerous lesions of internal carotid arteries should be operated on within the first 72 hours, if there are no accompanying changes requiring time for correction thereof.

[Method of surgical treatment of venous thrombosis using proximal protection]. / Sposob khirurgicheskogo lecheniia venoznogo tromboza s ispol'zovaniem proksimal'noi zashchity.

Pulmonary embolism ranks third among causes of death from cardiovascular diseases after acute coronary syndrome and impairment cerebral circulation. A factor provoking pulmonary embolism in the majority of cases is thrombosis of deep veins of lower limbs. Presented in the article is a clinical case report concerning treatment of a 35-year-old female patient with acute bilateral phlebothrombosis of internal iliac veins with floatation of thrombotic heads in the inferior vena cava and common iliac vein on the left. By means of a hybrid technique, we successfully performed operative intervention: thrombectomy from the inferior vena cava and common iliac veins on both sides with the use of proximal protection TREX (thromboextractor). Control X-ray contrast tomography and ultrasound examination of lower limb veins showed no evidence of rethrombosis. After surgical treatment, the woman received anticoagulant therapy. On POD 5, she was discharged home in a satisfactory condition.

[Carotid endarterectomy in acute period of ischemic stroke]. / Khirurgicheskaia revaskuliarizatsiia karotidnogo basseina v ostreishem periode ishemicheskogo insul'ta.

A review is devoted to carotid endarterectomy for symptomatic carotid stenosis in acute period of ischemic stroke. Patient selection criteria, dates of surgical intervention and perioperative risk were analyzed.

[Secondary epileptogenesis in the immature brain: a role of GABA]. / Vtorichnyi épileptogenez v nezrelom mozge: rol' GAMK.

Clinical studies show that the probability of recurrent epileptiform discharges and formation of an epileptic focus (epileptogenesis) in young children is much higher than in adults. Repetitive epileptiform discharges and their potential contribution to the mechanisms of the development of the epileptic focus - an important object of clinical and scientific research. This review is based on the data from animal studies, and summarizes the current understanding of the mechanisms underlying the increased excitability of the immature brain, the formation of a secondary epileptogenic focus, and the functional changes of neurons due to deleterious effects of repetitive epileptiform discharges on the excitation and inhibition in the immature neuronal networks. The review discusses the relevance of experimental data in light of the general mechanisms of epileptogenesis in infants and identifies the gaps in current scientific knowledge, including the relationship between the data obtained in animal studies and processes underlying human acquired epilepsy.

[Emergency prosthetic repair of a ruptured abdominal aortic aneurysm].

Presented herein is a case report regarding successful endovascular prosthetic repair of an abdominal aortic aneurysm in its retroperitoneal rupture in a 56-year-old male patient treated by implantation of the unilateral stent-graft «Aorfix¼, cross femoro-femoral bypass grafting, and ligation of the contralateral common iliac artery.

Reconstruction of the aortofemoral segment using a minilaparotomy access. Experience with 100 operations.

This paper analyzes the results of 100 aortofemoral reconstructions using a miniaccess (patient group I), performed between July 2002 and December 2004. Of these, 92 reconstructions were bilateral and 8 unilateral. The patients' age ranged within 29-83 years (mean 58.3+/-0.9 years). The access to the aorta was gained through a median minilaparotomy (MLT) measuring 5-12 cm in length. The proximal anastomosis was formed above or at the level of the inferior mesenterial artery. The intra- and postoperative data were compared with the results of 162 aortofemoral reconstructions performed using a standard laparotomy (StLT) group II. The times of operation and aortic clamping did not increase during MLT (the time of operation was 192.3+/-4.0 and 207.7+/-5.1 min., the time of aortic clamping 24.3+/-1,6 and 25.8+/-1.7 min in groups I and II respectively). The lowering of traumatic injury during MLT resulted in a decrease of the amount of myorelaxants (by 17.1%; P<0.001) and of the volume of intraoperative infusion (by 12.4%; p<0.05). The short-term postoperative period in group I patients ran a milder course. The painful syndrome was less pronounced and bowel function returned to normal earlier. The incidence of local vascular complications was not different (9.0% during MLT and 10.5% during StLT). In group I, the incidence of local non-vascular complications decreased (from 14.8 to 8.0%, p=0.15) due to the absence of eventrations. The incidence of systemic complications during MLT dropped from 21.0% to 11.0% (p=0.056). During StLT the postoperative lethality accounted for 3.1%, that during MLT for 1.0% (p=0.49). The postoperative hospital stay decreased by 27.8% (p<0.001).

Early development of neuronal activity in the primate hippocampus in utero.

Morphological studies suggest that the primate hippocampus develops extensively before birth, but little is known about its functional development. Patch-clamp recordings of hippocampal neurons and reconstruction of biocytin-filled pyramidal cells were performed in slices of macaque cynomolgus fetuses delivered by cesarean section. We found that during the second half of gestation, axons and dendrites of pyramidal cells grow intensively by hundreds of micrometers per day to attain a high level of maturity near term. Synaptic currents appear around midgestation and are correlated with the level of morphological differentiation of pyramidal cells: the first synapses are GABAergic, and their emergence correlates with the growth of apical dendrite into stratum radiatum. A later occurrence of glutamatergic synaptic currents correlates with a further differentiation of the axodendritic tree and the appearance of spines. Relying on the number of dendritic spines, we estimated that hundreds of new glutamatergic synapses are established every day on a pyramidal neuron during the last third of gestation. Most of the synaptic activity is synchronized in spontaneous slow ( approximately 0.1 Hz) network oscillations reminiscent of the giant depolarizing potentials in neonatal rodents. Epileptiform discharges can be evoked by the GABA(A) receptor antagonist bicuculline by the last third of gestation, and postsynaptic GABA(B) receptors contribute to the termination of epileptiform discharges. Comparing the results obtained in primates and rodents, we conclude that the template of early hippocampal network development is conserved across the mammalian evolution but that it is shifted toward fetal life in primate.

Neuronal mechanisms of the anoxia-induced network oscillations in the rat hippocampus in vitro.

1. A spindle of fast network oscillations precedes the ischaemia-induced rapid depolarisation in the rat hippocampus in vivo. However, this oscillatory pattern could not be reproduced in slices and the underlying mechanisms remain poorly understood. We have found that anoxia-induced network oscillations (ANOs, 20-40 Hz, lasting for 1-2 min) can be reproduced in the intact hippocampi of postnatal day P7-10 rats in vitro, and we have examined the underlying mechanisms using whole-cell and extracellular field potential recordings in a CA3 pyramidal layer. 2. ANOs were generated at the beginning of the anoxic depolarisation, when pyramidal cells depolarised to subthreshold values. Maximal power of the ANOs was attained when pyramidal cells depolarised to -56 mV; depolarisation above -47 mV resulted in a depolarisation block of pyramidal cells and a waning of ANOs. 3. A multiple unit activity in extracellular field recordings was phase locked to the negative and ascending phases of ANOs. Pyramidal cells recorded in current-clamp mode generated action potentials with an average probability of about 0.05 per cycle. The AMPA receptor-mediated EPSCs and the GABA receptor-mediated IPSCs in CA3 pyramidal cells were also phase locked with ANOs. 4. ANOs were prevented by tetrodotoxin and glutamate receptor antagonists CNQX and APV, and were slowed down by the allosteric GABA(A) receptor modulator diazepam. In the presence of the GABA(A) receptor antagonist bicuculline, ANOs were transformed to epileptiform discharges. 5. In the presence of the A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), the anoxia induced an epileptiform activity and no ANOs were observed. 6. In normoxic conditions, a rise of extracellular potassium to 10 mM induced an epileptiform activity. Increasing extracellular potassium in conjunction with a bath application of the adenosine A1 receptor agonist cyclopentyladenosine induced oscillations similar to ANOs. 7. Multisite recordings along the septo-temporal hippocampal axis revealed that ANOs and anoxic depolarisation originate in the temporal part, and propagate towards the septal pole at a speed of 1.9 mm x min(-1). 8. ANOs were observed starting from P7, i.e. at a developmental stage when the effects of GABA change from depolarisation to hyperpolarisation. 9. These results suggest that the synchronisation of anoxia-induced oscillations relies on synaptic mechanisms; that the inhibition by GABA and adenosine sets the tune for a generation of oscillations and prevents an epileptiform activity; and that a synchronous GABAergic inhibition is instrumental in a phase locking neuronal activity similarly to other types of oscillatory activities in the gamma frequency range.

Morphology of CA3 non-pyramidal cells in the developing rat hippocampus.

Although several investigations have shown that the local GABAergic circuit in the rat hippocampus is functional very early in development, this result has not been yet completed by the investigation of the full dendritic and axonal arborization of the neonatal interneurones. In the present study, intracellular injection of biocytin was used to assess the branching pattern of interneurones in the hippocampal CA3 region of rat between 2 and 6 days of age. Based on their dendritic morphology, the biocytin-filled interneurones were divided into four classes: bipolar, stellate, pyramidal-like and fusiform interneurones. About half of the biocytin-filled neonatal interneurones exhibited dendritic or somatic filopodial processes. The axonal arbors of the filled-interneurones were widely spread into the CA3 region, and in four out of nine cases extended beyond the CA3 region to branch into the CA1 region. These results show that, despite immature features, the filopodial processes, the hippocampal interneurones are well developed early in development at a time when their target cells, the pyramidal neurones, are still developing. These observations are consistent with a trophic role that GABA may play early in development.

[Assessment of the results of surgical treatment of multiple lesions of lower limb arteries]. / Otsenka rezul'tatov khirurgicheskogo lecheniia bol'nykh s mnozhestvennym porazheniem arterii nizhnikh konechnostei.

121 one-stage "two-floor" reconstructions were performed in multiple lesions of lower limbs arteries. Their results were compared with results of 197 reconstructions of aorto-iliac segment with revascularisation of the firifory of deep femoral artery (DFA). In immediate postoperative period better results were achieved after one-stage "two-floor" reconstructions. There were 70.9% of good results after revascularisation of DFA and 88.4%--after one-stage "two-floor" reconstructions. In long-term period (up to 5 years) after "two-floor" reconstructions the patency of the distal bypasses was lower than that of proximal bypasses since the second year of follow-up. Patency of the distal bypasses after one-stage "two-floor" reconstructions depends on a type of plastic material, location of distal anastomosis of the femoro-popliteal bypass and does not depend on location of the proximal anastomosis. Patency of combined bypasses was lower than one of autovenous bypasses and biografts since the second year of follow-up, patency of femoro-tibial bypasses was lower than that of femoro-popliteal bypasses since the third year of follow-up.

[Insecticidal activity of Bacillus thuringiensis cells]. / Entomotsidnaia aktivnost' bakterial'nykh kletok Bacillus thuringiensis.

The influence of sixteen different nutrient media on the entomopathogenic activity of three Bacillus thuringiensis strains was studied. The medium composition based on potato, yeast extract, and molasses was optimized. B. thuringiensis No 1 grown on the media No 7 and 9 displayed the highest entomopathogenic activity (94.3 and 90.6%, respectively).

Dual role of GABA in the neonatal rat hippocampus.

The effects of modulators of GABA-A receptors on neuronal network activity were studied in the neonatal (postnatal days 0-5) rat hippocampus in vitro. Under control conditions, the physiological pattern of activity of the neonatal hippocampal network was characterized by spontaneous network-driven giant depolarizing potentials (GDPs). The GABA-A receptor agonist isoguvacine (1-2 microM) and the allosteric modulator diazepam (2 microM) induced biphasic responses: initially the frequency of GDPs increased 3 to 4 fold followed by blockade of GDPs and desynchronization of the network activity. The GABA-A receptor antagonists bicuculline (10 microM) and picrotoxin (100 microM) blocked GDPs and induced glutamate (AMPA and NMDA)-receptor-mediated interictal- and ictal-like activities in the hippocampal slices and the intact hippocampus. These data suggest that at early postnatal ages GABA can exert a dual - both excitatory and inhibitory - action on the network activity.

Maturation of kainate-induced epileptiform activities in interconnected intact neonatal limbic structures in vitro.

In vivo studies suggest that ontogenesis of limbic seizures is determined by the development of the limbic circuit. We have now used the newly-developed in vitro intact interconnected neonatal rat limbic structures preparation to determine the developmental profile of kainate-induced epileptiform activity in the hippocampus and its propagation to other limbic structures. We report gradual alterations in the effects of kainate during the first postnatal week on an almost daily basis; from no epileptiform activity at birth, through interictal seizures around postnatal day (P) 2 and ictal seizures by the end of the first week. The developmental profile of kainate-induced hippocampal seizures is paralleled by the expression of postsynaptic kainate receptor-mediated currents in CA3 pyramidal cells. Intralimbic propagation of the hippocampal seizures is also age-dependent: whereas seizures readily propagate to the septum and to the contralateral hippocampus via the commissures on P2, propagation to the entorhinal cortex only takes place from P4 onwards. Finally, repeated brief applications of kainate to the hippocampus induce recurrent spontaneous glutamatergic ictal and interictal discharges which persist for several hours after the kainate is washed away and which replace the physiological pattern of network activity. Paroxysmal activities are thus generated by kainate in the hippocampus at an early developmental stage and are initially restricted to this structure. Before the end of the first week of postnatal life, kainate generates the epileptiform activities that may perturb activity-dependent mechanisms that modulate neuronal development. Although at this stage neurons are relatively resistant to the pathological effects of kainate, the epileptiform activities that it generates will perturb activity-dependent mechanisms that modulate neuronal development.

GABA is the principal fast-acting excitatory transmitter in the neonatal brain.

gamma-aminobutyric acid (GABA) is the principal neurotransmitter of inhibition in the adult mammalian brain. However, at early stages of development, including the embryonic period and first week of postnatal life, GABA plays the role of main neurotransmitter of excitation. The paradoxical excitatory effect of GABA is caused by an inverted chloride gradient and, therefore, a depolarizing direction of GABA type A (GABAA) receptor mediated responses. In addition, another type of GABAergic inhibition mediated by postsynaptic GABA type B (GABAB) receptors is not functional at early stage of life. In the neonatal rat hippocampus, GABA, acting via GABAA receptors, activates voltage-gated sodium and calcium channels and potentiates the activity of N-methyl-D-aspartate (NMDA) receptors by reducing their voltage-dependent Mg2+ block. The temporal window when GABA exerts excitatory actions coincides with a particular pattern of activity of hippocampal neuronal network that is characterized by periodical giant depolarizing potentials (GDPs) reminiscent of interictal-like epileptiform discharges. Recent studies have shown that GDPs result from the synchronous discharge of GABAergic interneurons and principal glutamatergic pyramidal cells, and they are mediated by the synergistic excitatory actions of GABAA and glutamate receptors. GDPs provide synchronous intracellular Ca2+ oscillations and may, therefore, be implicated in hebbian modulation of developing synapses and activity-dependent formation of the hippocampal network.

Three-independent-compartment chamber to study in vitro commissural synapses.

We describe a novel chamber in which the two intact neonatal rat hippocampi and the commissural fibers are placed in three independent compartments separated by latex membranes and perfused selectively with different solutions. A set of control tests showed that the compartments are well isolated: 1) methylene blue or eosin applied to one compartment did not diffuse to other compartments when verified via the microscope, and spectrophotometry revealed that <1/10.000th of the dye diffuses to other compartments; 2) tetrodotoxin (1 microM) applied to the commissural compartment blocked the synaptic responses evoked contralaterally without affecting those evoked on the ipsilateral side. This chamber enables a wide range of experiments that cannot be performed in conventional chambers, e.g., to study the maturation and plasticity of the commissural connections, bilateral synchronization of the rhythmic activities in the limbic system, commissural propagation of the epileptiform activities, etc.

Giant depolarizing potentials: the septal pole of the hippocampus paces the activity of the developing intact septohippocampal complex in vitro.

In neonatal hippocampal slices, recurrent spontaneous giant depolarizing potentials (GDPs) provide neuronal synchronized firing and Ca2+ oscillations. To investigate the possible role of GDPs in the synchronization of neuronal activity in intact neonatal limbic structures, we used multiple simultaneous electrophysiological recordings in the recently described preparation of intact neonatal septohippocampal complex in vitro. Combined whole-cell (in single or pairs of cells) and extracellular field recordings (one to five simultaneous recording sites) from the CA3 hippocampal region and various parts of the septum indicated that spontaneous GDPs, which can be initiated anywhere along the longitudinal hippocampal axis, are most often initiated in the septal poles of hippocampus and propagate to medial septum and temporal poles of both hippocampi simultaneously. GDPs were abolished in the medial septum but not in the hippocampus after surgical separation of both structures, suggesting hippocampal origin of GDPs. The preferential septotemporal orientation of GDP propagation observed in the intact hippocampus was associated with a corresponding gradient of GDP frequency in isolated portions of hippocampus. Accordingly, most GDPs propagated in the septotemporal direction in both septal and temporal hippocampal isolated halves, and whereas GDP frequency remained similar in the septal part of hippocampus after its surgical isolation, it progressively decreased in more temporally isolated portions of the hippocampus. Because GDPs provide most of the synaptic drive of neonatal neurons, they may modulate the development of neuronal connections in the immature limbic system.

A novel in vitro preparation: the intact hippocampal formation.

The intact hippocampal formation (IHF) of neonatal or young rats can be kept alive for an extended period in a fully submerged chamber with excellent morphological preservation. Field or patch-clamp recordings, intracellular Ca2+ measurements, and 3-D reconstruction of biocytin-filled neurons can be performed routinely. The generation and propagation of network-driven activities can be studied within the IHF or between connected intact structures such as the septum and the hippocampus or two hippocampi, and the use of a dual chamber enables the application of drugs separately to each structure. This preparation will be useful to study intact neuronal networks in the developing hippocampus in vitro.

Ca2+ oscillations mediated by the synergistic excitatory actions of GABA(A) and NMDA receptors in the neonatal hippocampus.

We asked whether GABA(A) and NMDA receptors may act in synergy in neonatal hippocampal slices, at a time when GABA exerts a depolarizing action. The GABA(A) receptor agonist isoguvacine reduced the voltage-dependent Mg2+ block of single NMDA channels recorded in cell-attached configuration from P(2-5) CA3 pyramidal neurons and potentiated the Ca2+ influx through NMDA channels. The synaptic response evoked by electrical stimulation of stratum radiatum was mediated by a synergistic interaction between GABA(A) and NMDA receptors. Network-driven Giant Depolarizing Potentials, which are a typical feature of the neonatal hippocampal network, provided coactivation of GABA(A) and NMDA receptors and were associated with spontaneous and synchronous Ca2+ increases in CA3 pyramidal neurons. Thus, at the early stages of development, GABA is a major excitatory transmitter that acts in synergy with NMDA receptors. This provides in neonatal neurons a hebbian stimulation that may be involved in neuronal plasticity and network formation in the developing hippocampus.

Synchronization of GABAergic interneuronal network in CA3 subfield of neonatal rat hippocampal slices.

1. Cell-attached and whole-cell recordings from interneurons localized in the stratum radiatum of the CA3 subfield (SR-CA3) of neonatal (postnatal days 2-5) rat hippocampal slices were performed to study their activity during the generation of GABAergic giant depolarizing potentials (GDPs) in CA3 pyramidal cells. 2. Dual recordings revealed that during the generation of GDPs in CA3 pyramidal cells, the interneurons fire bursts of spikes, on average 4.5 +/- 1.4 spikes per burst (cell-attached mode). There bursts were induced by periodical large inward currents (interneuronal GDPs) recorded in whole-cell mode. 3. Interneuronal GDPs revealed typical features of polysynaptic neuronal network-driven events: they were blocked by TTX and by high divalent cation medium and they could be evoked in an all-or-none manner by electrical stimulation in different regions of the hippocampus. The network elements required for the generation of GDPs are present in local CA3 circuits since spontaneous GDPs were present in the isolated CA3 subfield of the hippocampal slice. 4. Interneuronal GDPs were mediated by GABAA and glutamate receptors, since: (i) their reversal potential strongly depended on [Cl-]i; (ii) at the reversal potential of GABAA postsynaptic currents an inward component of GDPs was composed of events with the same kinetics as alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-mediated EPSCs; and (iii) once GABAA receptors were blocked intracellularly by dialysis with F(-)-MgATP-free solution, the remaining component of interneuronal GDPs reversed near 0 mV and rectified at membrane potentials more negative than -20 mV, suggesting an important contribution of NMDA receptors in addition to AMPA receptors. 5. In cell-attached recordings from interneurons, electrical stimulation in the stratum radiatum evoked a burst of spikes that corresponded to evoked GDPs. Pharmacological study of this response revealed that excitation of SR-CA3 interneurons during GDPs is determined by the co-operative depolarizing actions mediated by GABAA and glutamate (AMPA and NMDA) receptors. Interestingly, after blockade of AMPA receptors, GABAA receptor-mediated depolarization enabled the activation of NMDA receptors presumably via attenuation of their voltage-dependent magnesium block. 6. It is concluded that synchronous activation of SR-CA3 interneurons during generation of GDPs is mediated synaptically and is determined by the co-operation of (i) excitatory GABAergic connections between interneurons and (ii) glutamatergic connections to interneurons originating presumably from the pyramidal cells.