Microscopic study of the Halperin-Laughlin interface through matrix product states.

Interfaces between topologically distinct phases of matter reveal a remarkably rich phenomenology. We study the experimentally relevant interface between a Laughlin phase at filling factor ν = 1/3 and a Halperin 332 phase at filling factor ν = 2/5. Based on our recent construction of chiral topological interfaces (Nat. Commun. https://doi.org/10.1038/s41467-019-09168-z ; 2019), we study a family of model wavefunctions that captures both the bulk and interface properties. These model wavefunctions are built within the matrix product state framework. The validity of our approach is substantiated through extensive comparisons with exact diagonalization studies. We probe previously unreachable features of the low energy physics of the transition. We provide, amongst other things, the characterization of the interface gapless mode and the identification of the spin and charge excitations in the many-body spectrum. The methods and tools presented are applicable to a broad range of topological interfaces.

Model states for a class of chiral topological order interfaces.

Interfaces between topologically distinct phases of matter reveal a remarkably rich phenomenology. To go beyond effective field theories, we study the prototypical example of such an interface between two Abelian states, namely the Laughlin and Halperin states. Using matrix product states, we propose a family of model wavefunctions for the whole system including both bulks and the interface. We show through extensive numerical studies that it unveils both the universal properties of the system, such as the central charge of the gapless interface mode and its microscopic features. It also captures the low energy physics of experimentally relevant Hamiltonians. Our approach can be generalized to other phases described by tensor networks.

Anoxic LTP sheds light on the multiple facets of NMDA receptors.

Hippocampal neurones in the CA1 region have become a model system to study the mechanisms of long-term potentiation (LTP) and memory processes. The CA1 region is also highly vulnerable to ischaemic or anoxic episodes which induce a selective and delayed degeneration of pyramidal neurones. In CA1 neurones, anoxic episodes generate a novel form of LTP to which we refer as anoxic LTP. In common with tetanic LTP, the induction of anoxic LTP is voltage- and NMDA receptor-dependent. However, in contrast with tetanic LTP, the expression of anoxic LTP is mediated exclusively by NMDA receptors. These observations suggest that anoxic-ischaemic episodes trigger a switch in favour of NMDA receptor-operated synaptic transmission. We suggest that the multiple forms of NMDA receptor-dependent LTPs are determined by extracellular and intracellular modulatory sites of this receptor.

Cycloheximide Reduces the Effects of Anoxic Insult In Vivo and In Vitro.

In vivo and in vitro techniques were utilized to examine the influence of a protein synthesis blocker, cycloheximide (CHX), on the damaging effects of anoxia in the rat. CHX administered 1 h before transient (30 min) forebrain ischaemia increased the survival of animals, decreased body weight loss and reduced the occurrence of delayed degeneration in the CA1 pyramidal region. The same dose of CHX injected 1 h after ischaemia induced status epilepticus, a decrease in survival rate, and did not reduce weight loss or CA1 damage in any of the surviving rats. Electrophysiological techniques were then used to determine the effects of various periods of anoxia and aglycaemia (AA) on CA1 field excitatory postsynaptic potentials (EPSPs) in hippocampal slices incubated in the presence or absence of CHX. In CHX-treated slices, recuperation of EPSP amplitude (45 +/- 16%) was significantly greater than in control slices (9 +/- 9%) following an AA episode of 3 min 45 s. No difference was seen in the percent recuperation of EPSPs in the control and CHX-treated slices after shorter or longer episodes of AA. From these studies, it appears that CHX protects against the damaging effect of ischaemia in vivo or AA in vitro.

Developmental and regional differences in the vulnerability of rat hippocampal slices to lack of glucose.

Field excitatory postsynaptic potentials were recorded in stratum radiatum of CA1 and CA3 in submerged hippocampal slices from adult or newborn (postnatal days 5-25) Wistar rats. In adult slices, excitatory postsynaptic potentials were depressed by glucose removal ("aglycemia") more rapidly and to a greater extent in CA1 than in CA3 [respective mean times to 50% reduction in peak amplitude were 7.5 +/- 0.83 (standard error) min and 12.5 +/- 0.27 (standard error) min]. Subsequent recovery of excitatory postsynaptic potentials in normoglycemic medium was correspondingly quicker in CA3 than in CA1. Transmission failure at the synapses was indicated by the preservation of the afferent volley, and sharp depression of synaptic input-output plots. In the early postnatal period, CA1 excitatory postsynaptic potentials were much more resistant to aglycemia, substantially persisting for as long as 75 min, with full subsequent recovery in normoglycemic medium. The higher resistance of slices from newborn rats progressively disappeared over the first two postnatal weeks.

Activators of ATP-sensitive K+ channels reduce anoxic depolarization in CA3 hippocampal neurons.

In CA3 hippocampal neurons of the rat, brief anoxic episodes produce a depolarization which is probably due to a synaptic release of glutamate. Diazoxide, an activator of ATP-sensitive K+ channels (K+ ATP), blocks the anoxic depolarization and has no effect in control oxygenated artificial cerebrospinal fluid. The hormone somatostatin which activates K+ ATP channels in the pancreas also reduces the anoxic depolarization in CA3 neurons. We suggest that drugs that open K+ ATP channels may constitute a novel approach to selectivity reducing the deleterious effects of excessive release of glutamate during anoxia without producing a generalized blockade of glutamatergic synaptic transmission.

Hippocampal damage induced by ischemia and intra-amygdaloid kainate injection: effect on N-methyl-D-aspartate, N-(1-[2-thienyl]cyclohexyl)piperidine and glycine binding sites.

The N-methyl-D-aspartate receptor channel-complex is widely distributed in the hippocampus, particularly in the CA1 region, in the terminal field of CA3 pyramidal axons and in the fascia dentata, in the terminal field of the perforant pathway. In the present study, we have examined, in the rat, the effect of specific lesions of various neuronal populations of the hippocampus on the distribution of several markers of the N-methyl-D-aspartate receptor-channel complex. Anoxic-ischemic treatment produced a destruction of CA1 pyramidal cells (postsynaptic element): this was associated with a 50% loss of N-methyl-D-aspartate, glycine and N-(1-phenylcyclohexyl)piperidine binding sites. In contrast, the destruction of CA3 pyramidal cells and their axons (presynaptic element) by kainate treatment did not induce significant changes in the density of binding sites. The present results therefore strongly support an exclusively postsynaptic localization of the N-methyl-D-aspartate receptor-channel complex in CA1; the possibility of a localization of the remaining binding sites on glial cells or interneurons is discussed. In the molecular layer of the fascia dentata, the anoxic-ischemic treatment produced a partial destruction of the median perforant pathway (presynaptic element) associated with a decrease in the density of N-methyl-D-aspartate, N-(1-[2-thienyl]cyclohexyl)piperidine and glycine binding sites; this suggests that, in contrast to CA1, in the molecular layer of the fascia dentata, N-methyl-D-aspartate receptor-binding sites are located both pre- and postsynaptically.

Transient cerebral ischemia induces changes in SRIF mRNA in the fascia dentata.

A transient cerebral ischemia produced in rats by 4-vessel occlusion, produces with a delay of 24 h a fall in the number of somatostatin-containing neurons. In the present study we show that this loss is preceded by a loss of somatostatin mRNA that starts as soon as 30 min after the anoxic episode. By 24 h of revascularization the surviving somatostatinergic hilar cells present a transient recovery of hybridization signal. This effect could be related to a previously reported increase in intracellular calcium.

A new method for the measurement of endogenous transmitter release in localized regions of hippocampal slices.

We describe here a method that allows measurement of the release of endogenous amino acids from localized regions of brain slices combined with conventional electrophysiological experiments. Hippocampal slices were placed in fully submerged chambers and a cannula was positioned just above the dendritic layers of CA1. The cannula was connected to a peristaltic pump and the content of amino acids in the perfusate was measured by HPLC. Extracellular field potentials were concomitantly recorded. Stable levels of aspartate and glutamate were found above the stratum radiatum of CA1. No detectable release was found when the cannula was located above the alveus, the fimbria or in the effluent of the slice. A pulse of K+ (50 mM) produced a brief 3-fold increase in glutamate, aspartate and a detectable release of GABA in CA1. Brief high frequency trains (10 Hz) also increased significantly the release. This method will be useful in determining alterations in transmitter release in the slice in relation to anoxia, epilepsy and long term potentiation.

The NMDA receptor contributes to anoxic aglycemic induced irreversible inhibition of synaptic transmission.

Percent recovery of CA1 field EPSP amplitude following various anoxic aglycemic (AA) periods was examined in rat hippocampal slices superfused with MK-801 (0.1 microM, 1 microM, 10 microM) or Mg(2+)-free artificial cerebrospinal fluid. Slices treated with 0.1 microM MK-801 showed greater percent recuperation of EPSP amplitude following 3 min 30 s of AA (36 +/- 12% vs 6 +/- 4% in controls). Higher concentrations of MK-801 resulted in a greater recovery of EPSP amplitudes in more than one time period of AA, with 10 microM MK-801 providing protection in up to 4 min 30 s AA. Percent recuperation of EPSP amplitude was smaller in Mg(2+)-free slices following 2 min (34 +/- 15% vs 81 +/- 11% in controls) and 2 min 30 (25 +/- 14% vs 77 +/- 10% in controls) of AA. These results suggest that the activation of the N-methyl-D-aspartate (NMDA) receptor channel may contribute to irreversible AA induced synaptic failure in CA1.

Effects of kainic acid-induced seizures and ischemia on c-fos-like proteins in rat brain.

We have analyzed the brain pattern and time-course of c-fos-like proteins expression in kainic acid-induced seizures in the rat. C-fos-like immunoreactivity increased initially in the hippocampus, notably in the dentate gyrus, at the time of the first limbic motor seizure (90 min after kainate). C-fos-like labelling progressively involved different structures of the limbic system when the rats manifested a permanent epileptic state (3-6 h). The labelling was still conspicuous 12 h after kainate treatment and progressively declined to reach control levels 48 h after kainate. This time-course is similar to that produced by kainic acid on 2-deoxyglucose consumption and correlates with the electrographic changes previously described, supporting the idea that c-fos-like immunostaining may provide a useful marker of neuronal activity, with a cellular resolution. Since anoxic-ischemic treatment produces a very slight and transient increase in c-fos-like immunostaining restricted to the fascia dentata, c-fos-like expression is seizure-related and not due to a local hypoxia or ischemia.

Intracellular injection of a Ca2+ chelator prevents generation of anoxic LTP.

1. The effects of intracellular injection of Ca2+ chelator 1,2-bis (2-aminophenoxy) ethane N,N,N',N'-tetra-acetic acid (BAPTA, 50 mM) on anoxia-aglycemia-induced long-term potentiation (LTP) were investigated in the CA1 region of hippocampal slices with the use of extra- and intracellular recording techniques. Experiments were performed in artificial cerebrospinal fluid (ACSF) containing 10 microM bicuculline and 10 microM 6-cyano-7-nitroquinoxaline- 2,3-dione (CNQX) to pharmacologically isolate N-methyl-D-aspartate (NMDA)-receptor-mediated responses. NMDA-receptor-mediated excitatory postsynaptic potentials (EPSPs) and field potentials were evoked by stimulation of the Schaffer collateral/commissural pathway in the presence of 0.3 mM MgCl2 and 10 microM glycine to promote NMDA-receptor-mediated responses. Under these conditions, application of 50 microM D-2-amino-phosphono-valerate (D-APV) abolished EPSPs and field potentials. 2. Anoxic-aglycemic (AA) episodes (duration 2-2.5 min) potentiated the initial slope (measured within 3 ms from the onset of the synaptic responses) of EPSPs by 108 +/- 14.3% (mean +/- SE, P = 0.0012, n = 7). We refer to this LTP of NMDA-receptor-mediated synaptic responses as anoxic LTP. 3. Intracellular injection of the Ca2+ chelator BAPTA (with the intracellular recording electrode filled with 50 mM BAPTA in 3 M KCl) prevented anoxic LTP. Thirty to 40 min after the AA episode, in BAPTA-loaded cells, the initial slope of the EPSPs was not significantly changed (+7.12 +/- 5%, P = 0.35, n = 5). In contrast, the initial slope of the field potentials, measured at the same time in the same slices, was persistently increased (+49 +/- 2.8%, P = 0.0022, n = 5). 4. High-frequency tetanic stimulation (100 Hz for 500 ms, 2 times, 30 s apart) of the Schaffer collateral/commissural pathway, applied > 0.5 h after the AA episode, induced an additional significant and persistent increase in the initial slope of the field potential (tetanic LTP, +35.4 +/- 9.8%, P = 0.012, n = 5). In BAPTA-loaded cells, there was no further change in the initial slope of the EPSP (+3.9 +/- 3.4%, P = 0.205, n = 5) after the tetanic stimulation. 5. We also report that AA episodes or tetanic stimulation induced a persistent increase in a late synaptic component that was blocked by 50 microM D-APV. This late component was mediated polysynaptically, because its time to peak decreased with increasing stimulation intensities and it was strongly reduced by high-divalent-cation superfusate (ACSF containing 7 mM Ca2+). This component, which had a delay of approximately 8-30 ms, contaminated mainly the peak amplitude and the decay of the monosynaptic response without affecting its initial slope. Thus the measure of the initial slope takes into account only the early phase of the monosynaptic response. 6. We conclude that 1) a rise in intracellular Ca2+ is necessary to generate anoxic LTP of NMDA-receptor-mediated responses, as is the case for tetanic LTP; and 2) in the presence of bicuculline and low extracellular Mg2+, AA episodes and tetanic stimulations induced a long-lasting enhancement of a polysynaptic component mediated or controlled by NMDA receptors.

Glutamate metabotropic receptors increase a Ca(2+)-activated nonspecific cationic current in CA1 hippocampal neurons.

1. We studied the currents evoked in CA1 pyramidal neurons by the selective metabotropic glutamate receptor (mGluR) agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD; 100 microM, 2.30-5 min) with the single-electrode voltage-clamp technique in the continuous presence of tetrodotoxin (1 microM), bicuculline (10 microM), 6-cyano-7-nitroquinoxaline-2,3-dione (15 microM), and D-2-amino-5-phosphonovaleric acid (50 microM) to depress action potentials and synaptic activity. Microelectrodes were filled with 3M CsCl or 2 M Cs2SO4. 2. With CsCl-filled microelectrodes, bath application of 1S,3R-ACPD induced an inward current of -308 +/p 50 (SE) pA amplitude [holding potential (VH -60 mV, n = 12)] associated with a conductance decrease (26.5 +/- 5.6%, P < or = 0.0022, n = 12). The current-voltage (I-V) relation of the 1S,3R-ACPD-induced (difference) current investigated using ramp voltage commands from -130 to +10 mV had a V shape with two reversal potentials: -99.6 +/- 3.4 and -17.5 +/- 3.0 mV (n = 12). 3. In contrast, in the presence of external K+ channel blockers (2 mM Ba2+ and 6 mM Cs+ or 25 mM tetraethylammonium, 6 mM Cs+, and 3 mM 4-aminopyridine), 1S,3R-ACPD also generated an inward current, albeit of smaller amplitude (-114.2 +/- 27.5 pA, P < or = 0.003, VH -60 mV, n = 8). This current was associated with a conductance increase (20.7 +/- 3.1%, P < or = 0.0117, n = 8), decreased linearly with depolarization (from -130 to -60 mV), and reversed polarity at an estimated potential of -20.7 +/- 3.6 mV (n = 8). We refer to this current recorded in the presence of K+ channel blockers as IACPD. 4. In the presence of Cd2+ (200 microM, to block voltage-dependent Ca2+ channels that are readily activated in the presence of K+ channel blockers) and a low Ca2+ concentration (100 microM), IACPD decreased linearly from -130 to +10 mV and reversed polarity at -15.8 +/- 8.5 mV (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Sulphonylureas reduce the slowly inactivating D-type outward current in rat hippocampal neurons.

1. Using intracellular recording in hippocampal slices, we have examined, in CA3 pyramidal neurons, the effects of sulphonylureas (blockers of ATP-sensitive K+ channels) on the slowly inactivating D-type K+ current (ID). 2. In the presence of TTX (1 microM) to block Na+ currents, ID had the following characteristics: activation by large depolarizing pulses from membrane potentials negative to -75 mV, slow inactivation kinetics, high sensitivity to 4-aminopyridine (4-AP, 3-40 microM), insensitivity to tetraethylammonium (TEA, 10 mM), Cs+ (3 mM) and carbachol (50 microM). 3. Applications of glibenclamide (10 microM) did not modify the input conductance of the cell, but reduced the amplitude of ID by 31.2 +/- 5.6% (n = 16), without altering its voltage dependence and inactivation kinetics. The effects were usually reversible. 4. Glibenclamide also reduced ID in the presence of TEA (10 mM), Cs+ (3 mM) and carbachol (50 microM), to block several K+ currents (IK, IC, IQ, IM), as well as kynurenate (1 mM) and bicuculline (10 microM) to block on-going synaptic currents mediated by activation of non-NMDA (N-methyl-D-aspartate) and GABA (gamma-aminobutyrate)-A receptors, respectively. 5. Comparable depressions of ID were produced by two other sulphonylureas: gliquidone (10 microM), 42.6 +/- 7.9% (n = 13) and tolbutamide (500 microM), 39.1 +/- 12.8 (n = 8). 6. It is concluded that, in the central nervous system, sulphonylureas can modulate K+ currents which are not generated by ATP-sensitive K+ channels.

Glibenclamide depresses the slowly inactivating outward current (ID) in hippocampal neurons.

Sulphonylurea drugs, such as glibenclamide and tolbutamide, are widely used as selective blockers of adenosine triphosphate-sensitive K channels. In experiments on hippocampal slices (from Wistar rats) glibenclamide (and possibly gliquidone and tolbutamide) significantly reduced the highly voltage-dependent, 4-aminopyridine-sensitive D-type outward current of CA3 neurons. Judging by these observations, the sulphonylureas may not be as selective as generally believed.

The K+ channel opener diazoxide enhances glutamatergic currents and reduces GABAergic currents in hippocampal neurons.

1. The effect of diazoxide, an opener of ATP-sensitive K+ channels (KATP channels) has been investigated in the rat hippocampal slices by the use of extracellular and intracellular recording techniques. 2. In control solution, diazoxide enhanced the CA1 and CA3 field excitatory postsynaptic potentials (EPSPs) and produced interictal activities in CA3. These effects were neither prevented by KATP blockers, including glibenclamide (3-30 microM) or tolbutamide (500 microM), nor mimicked by another KATP opener such as galanine (1 microM); thus these effects are probably not mediated by KATP channels. 3. Using intracellular recording, we then studied, in CA3 pyramidal neurons, the effect of diazoxide on the EPSPs and the fast and slow inhibitory postsynaptic potentials (IPSPs). 4. In presence of bicuculline (10 microM) and phaclofen (50 microM), to block, respectively, fast and slow IPSPs, diazoxide reversibly enhanced the EPSPs. 5. In presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM), to block EPSPs, diazoxide reversibly decreased both fast and slow IPSPs. 6. These effects of diazoxide on the EPSPs and fast and slow IPSPs were associated neither with a change of the reversal potential of the EPSPs or the fast and slow IPSPs nor with a change of the input resistance and membrane potential. 7. Using single electrode voltage-clamp technique, we then tested the effects of diazoxide on the currents generated by applications of glutamate or gamma-aminobutyric acid (GABA) -A and -B analogues. 8. In presence of tetrodotoxin (TTX; 1 microM), diazoxide reversibly enhanced the peak currents evoked by alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA; 3-5 microM), quisqualate (5-10 microM) and N-methyl-D-aspartate (NMDA; 10 microM), but not those evoked by kainate (1-3 microM). 9. In presence of TTX (1 microM), diazoxide reversibly decreased the GABA- (1-5 mM), isoguvacine- (30-60 microM), and baclofen- (10-30 microM) mediated peak currents. 10. It is concluded that, in the hippocampus, diazoxide enhances the excitatory glutamatergic currents and reduces the GABAergic inhibition, thus generating paroxystic activities. We suggest that these effects are mediated by second messenger cascades.

A long-lasting calcium-activated nonselective cationic current is generated by synaptic stimulation or exogenous activation of group I metabotropic glutamate receptors in CA1 pyramidal neurons.

We have shown previously that a selective metabotropic glutamate receptor (mGluR) agonist, 1S,3R-1-aminocyclo-pentane-1, 3-dicarboxylate (1S,3R-ACPD), evokes an inward current in CA1 pyramidal neurons of rat hippocampal slices in the presence of K+ channel blockers (). This current has been characterized as a Ca2+-activated nonselective cationic (CAN) current. Using whole-cell patch-clamp recordings and intracellular dialysis, we now have identified the mGluR subtype and the mechanisms underlying the CAN current (ICAN) and report for the first time the presence of a synaptic ICAN in the mammalian CNS. First, we have shown pharmacologically that activation of ICAN by 1S,3R-ACPD involves the group I mGluRs (and not the groups II and III) and a G-protein-dependent process. We also report that ICAN is modulated by the divalent cations (Mg2+, Cd2+, and Zn2+). Second, we have isolated a slow synaptic inward current evoked by a high-frequency stimulation in the presence of K+ channel blockers, ionotropic glutamate, and GABAA receptor antagonists. This current shows similar properties to the exogenously evoked ICAN: its reversal potential is close to the reversal potential of the 1S, 3R-ACPD-evoked ICAN, and it is G-protein- and Ca2+-dependent. Because the amplitude and duration of ICAN increased in the presence of a glutamate uptake blocker, we suggest that this synaptic current is generated via the activation of mGluRs. We propose that the synaptic ICAN, activated by a brief tetanic stimulation and leading to a long-lasting inward current, may be involved in neuronal plasticity and synchronized network-driven oscillations.

Blocking GABA(A) inhibition reveals AMPA- and NMDA-receptor-mediated polysynaptic responses in the CA1 region of the rat hippocampus.

We have investigated the conditions required to evoke polysynaptic responses in the isolated CA1 region of hippocampal slices from Wistar adult rats. Experiments were performed with extracellular and whole cell recording techniques. In the presence of bicuculline (10 microM), 6-cyano-7-nitroquinoxaline-2-3-dione (10 microM), glycine (10 microM), and a low external concentration of Mg2+ (0.3 mM), electrical stimulation of the Schaffer collaterals/commissural pathway evoked graded N-methyl-D-aspartate (NMDA)-receptor-mediated late field potentials in the stratum radiatum of the CA1 region. These responses were generated via polysynaptic connections because their latency varied strongly and inversely with the stimulation intensity and they were abolished by a high concentration of divalent cations (7 mM Ca2+). These responses likely were driven by local collateral branches of CA1 pyramidal cell axons because focal application of tetrodotoxin (30 microM) in the stratum oriens strongly reduced the late synaptic component and antidromic stimulation of CA1 pyramidal cells could evoke the polysynaptic response. Current-source density analysis suggested that the polysynaptic response was generated along the proximal part of the apical dendrites of CA1 pyramidal cells (50-150 microm below the pyramidal cell layer in the stratum radiatum). In physiological concentration of Mg2+ (1.3 mM), the pharmacologically isolated NMDA-receptor-mediated polysynaptic response was abolished. In control artificial cerebrospinal fluid (with physiological concentration of Mg2+), bicuculline ( 10 microM) generated a graded polysynaptic response. Under these conditions, this response was mediated both by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/NMDA receptors. In the presence of D-2-amino-5-phosphonovalerate (50 microM), the polysynaptic response could be mediated by AMPA receptors, although less efficiently. In conclusion, suppression of gamma-aminobutyric acid-A inhibition reveals glutamate receptor-mediated network-driven events in the isolated CA1 region. These polysynaptic responses are mediated by AMPA and/or NMDA receptors depending on the pharmacological conditions and the external concentration of Mg2+ used. We suggest that these responses are driven by local recurrent collaterals of CA1 pyramidal cells.