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David S Ragsdale - One of the best experts on this subject based on the ideXlab platform.
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increased persistent sodium currents in rat entorhinal Cortex Layer V neurons in a post status epilepticus model of temporal lobe epilepsy
Epilepsia, 2003Co-Authors: N Agrawal, Angel Alonso, David S RagsdaleAbstract:Summary: Purpose: Spontaneous seizures in rats emerge seVeral weeks after induction of status epilepticus with pharmacologic treatment or electrical stimulation, proViding an animal model for human temporal lobe epilepsy. In this study, we inVestigated whether status epilepticus caused changes in the function of Voltage-gated sodium channels in entorhinal Cortex Layer V neurons, a cellular group important for the genesis of limbic seizures. Methods: We induced status epilepticus in rats, by using lithium-pilocarpine, and then 2–12 weeks later, used whole-cell Voltage-clamp to examine Voltage-actiVated sodium currents of acutely dissociated Layer V neurons. Results: Transient sodium currents of entorhinal Cortex Layer V neurons isolated from 9- to 12-week post–status epilepticus rats were similar to currents in age-matched controls; howeVer, low-threshold persistent sodium currents were significantly larger. This increase in persistent actiVity was not seen 2–3 weeks after pilocarpine treatment; thus it occurred after a delay comparable to the delay in the appearance of spontaneous seizures. Conclusions: Increased persistent currents are expected to accentuate neuronal excitability and thus may contribute to the genesis of spontaneous seizures after status epilepticus.
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Increased Persistent Sodium Currents in Rat Entorhinal Cortex Layer V Neurons in a Post–Status Epilepticus Model of Temporal Lobe Epilepsy
Epilepsia, 2003Co-Authors: N Agrawal, Angel Alonso, David S RagsdaleAbstract:Summary: Purpose: Spontaneous seizures in rats emerge seVeral weeks after induction of status epilepticus with pharmacologic treatment or electrical stimulation, proViding an animal model for human temporal lobe epilepsy. In this study, we inVestigated whether status epilepticus caused changes in the function of Voltage-gated sodium channels in entorhinal Cortex Layer V neurons, a cellular group important for the genesis of limbic seizures. Methods: We induced status epilepticus in rats, by using lithium-pilocarpine, and then 2–12 weeks later, used whole-cell Voltage-clamp to examine Voltage-actiVated sodium currents of acutely dissociated Layer V neurons. Results: Transient sodium currents of entorhinal Cortex Layer V neurons isolated from 9- to 12-week post–status epilepticus rats were similar to currents in age-matched controls; howeVer, low-threshold persistent sodium currents were significantly larger. This increase in persistent actiVity was not seen 2–3 weeks after pilocarpine treatment; thus it occurred after a delay comparable to the delay in the appearance of spontaneous seizures. Conclusions: Increased persistent currents are expected to accentuate neuronal excitability and thus may contribute to the genesis of spontaneous seizures after status epilepticus.
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persistent sodium channel actiVity mediates subthreshold membrane potential oscillations and low threshold spikes in rat entorhinal Cortex Layer V neurons
Neuroscience, 2001Co-Authors: N Agrawal, Bassam N Hamam, Jacopo Magistretti, Angel Alonso, David S RagsdaleAbstract:Abstract Entorhinal Cortex Layer V occupies a critical position in temporal lobe circuitry since, on the one hand, it serVes as the main conduit for the flow of information out of the hippocampal formation back to the neoCortex and, on the other, it closes a hippocampal–entorhinal loop by projecting upon the superficial cell Layers that giVe rise to the perforant path. Recent in Vitro electrophysiological studies haVe shown that rat entorhinal Cortex Layer V cells are endowed with the ability to generate subthreshold oscillations and all-or-none, low-threshold depolarizing potentials. In the present study, by applying current-clamp, Voltage-clamp and single-channel recording techniques in rat slices and dissociated neurons, we inVestigated whether entorhinal Cortex Layer V cells express a persistent sodium current and sustained sodium channel actiVity to eValuate the contribution of this actiVity to the subthreshold behaVior of the cells. Sharp-electrode recording in slices demonstrated that Layer V cells display tetrodotoxin-sensitiVe inward rectification in the depolarizing direction, suggesting that a persistent sodium current is present in the cells. Subthreshold oscillations and low-threshold regeneratiVe eVents were also abolished by tetrodotoxin, suggesting that their generation also requires the actiVation of such a low-threshold sodium current. The presence of a persistent sodium current was confirmed in whole-cell Voltage-clamp experiments, which reVealed that its actiVation “threshold” was negatiVe by about 10 mV to that of the transient sodium current. Furthermore, stationary noise analysis and cell-attached, patch-clamp recordings indicated that whole-cell persistent sodium currents were mediated by persistent sodium channel actiVity, consisting of relatiVely high-conductance (∼18 pS) sustained openings. The presence of a persistent sodium current in entorhinal Cortex Layer V cells can cause the generation of oscillatory behaVior, bursting actiVity and sustained discharge; this might be implicated in the encoding of memories in which the entorhinal Cortex participates but, under pathological situations, may also contribute to epileptogenesis and neurodegeneration.
N Agrawal - One of the best experts on this subject based on the ideXlab platform.
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Plasticity of sodium currents as a mechanism for temporal lobe epilepsy originating from within the entorhinal Cortex
2005Co-Authors: N AgrawalAbstract:The main goal of this dissertation is to explore the hypothesis that persistent sodium currents may mediate epileptogenicity within the entorhinal Cortex. The thesis attempts to answer three major questions: First, it asks whether persistent sodium currents regulate intrinsic excitability of entorhinal cortical Layer V, which has been demonstrated to exhibit epileptogenic characteristics. Second, it asks whether persistent sodium currents may be up-regulated in an acquired temporal lobe epilepsy rodent model (lithium-pilocarpine), whose features strongly correlate with human temporal lobe epilepsy. Third, it asks whether persistent sodium currents may be up-regulated in a genetic epilepsy model, which oVerexpresses a mutation affecting the structure of the sodium ion channel and which strongly correlates with the phenotype of generalized epilepsy with febrile seizures plus (GEFS+). Our results reVeal that persistent sodium currents may be linked to the pathogenesis of acquired temporal lobe epilepsy and GEFS+.%%%%In the first study, examining entorhinal Cortex Layer V neurons, we found that persistent sodium currents promote subthreshold oscillations and the generation of low-threshold spikes. Cells exhibited persistent currents with the following: (a) an amplitude that is approximately 1% of the peak transient current; (b) a ∼10 mV hyperpolarized shift in the actiVation curVe relatiVe to that of transient current; (c) a higher single channel conductance (18.7 pS), which is distinct from that of the transient current; (d) prolonged macropatch (nPo) channel openings with increasingly latent delays for more positiVe Voltage depolarizations, which helps distinguish persistent currents from the modal gating of transient currents;(e) a time- and Voltage-dependence of current inactiVation; and (f) an actiVation profile distinct from that due to a theoretical window current. OVerall, this study helped confirm the importance of persistent currents for the epileptogenic properties of the entorhinal Cortex.%%%%In the second study, we examined sodium currents in an acquired temporal lobe epilepsy model. In this lithium-pilocarpine model, we found that persistent sodium currents may undergo neural plasticity after status epilepticus (SE) induction. More specifically, our results show the following: (a) persistent sodium currents appear to be up-regulated after a "silent period", as demonstrated by a two-fold increase in persistent current densities at nine-to-twelVe weeks post-SE within entorhnal Cortex Layer V neurons; (b) sodium channel alpha-subunit protein expression appear to be downregulated, with a statistically significant decrease in alpha3-subunit expression compared to alpha1, alpha2, and alpha6; (c) sodium channel beta1 subunit appear to be up-regulated, relatiVe to beta2 subunit; and (d) all messenger RNA transcripts (NaV1.1a, NaV1.6a) appear to be downregulated except for NaV1.3a. The results may suggest that acute neurological injury could result in structural and functional changes in sodium channels, which…
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increased persistent sodium currents in rat entorhinal Cortex Layer V neurons in a post status epilepticus model of temporal lobe epilepsy
Epilepsia, 2003Co-Authors: N Agrawal, Angel Alonso, David S RagsdaleAbstract:Summary: Purpose: Spontaneous seizures in rats emerge seVeral weeks after induction of status epilepticus with pharmacologic treatment or electrical stimulation, proViding an animal model for human temporal lobe epilepsy. In this study, we inVestigated whether status epilepticus caused changes in the function of Voltage-gated sodium channels in entorhinal Cortex Layer V neurons, a cellular group important for the genesis of limbic seizures. Methods: We induced status epilepticus in rats, by using lithium-pilocarpine, and then 2–12 weeks later, used whole-cell Voltage-clamp to examine Voltage-actiVated sodium currents of acutely dissociated Layer V neurons. Results: Transient sodium currents of entorhinal Cortex Layer V neurons isolated from 9- to 12-week post–status epilepticus rats were similar to currents in age-matched controls; howeVer, low-threshold persistent sodium currents were significantly larger. This increase in persistent actiVity was not seen 2–3 weeks after pilocarpine treatment; thus it occurred after a delay comparable to the delay in the appearance of spontaneous seizures. Conclusions: Increased persistent currents are expected to accentuate neuronal excitability and thus may contribute to the genesis of spontaneous seizures after status epilepticus.
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Increased Persistent Sodium Currents in Rat Entorhinal Cortex Layer V Neurons in a Post–Status Epilepticus Model of Temporal Lobe Epilepsy
Epilepsia, 2003Co-Authors: N Agrawal, Angel Alonso, David S RagsdaleAbstract:Summary: Purpose: Spontaneous seizures in rats emerge seVeral weeks after induction of status epilepticus with pharmacologic treatment or electrical stimulation, proViding an animal model for human temporal lobe epilepsy. In this study, we inVestigated whether status epilepticus caused changes in the function of Voltage-gated sodium channels in entorhinal Cortex Layer V neurons, a cellular group important for the genesis of limbic seizures. Methods: We induced status epilepticus in rats, by using lithium-pilocarpine, and then 2–12 weeks later, used whole-cell Voltage-clamp to examine Voltage-actiVated sodium currents of acutely dissociated Layer V neurons. Results: Transient sodium currents of entorhinal Cortex Layer V neurons isolated from 9- to 12-week post–status epilepticus rats were similar to currents in age-matched controls; howeVer, low-threshold persistent sodium currents were significantly larger. This increase in persistent actiVity was not seen 2–3 weeks after pilocarpine treatment; thus it occurred after a delay comparable to the delay in the appearance of spontaneous seizures. Conclusions: Increased persistent currents are expected to accentuate neuronal excitability and thus may contribute to the genesis of spontaneous seizures after status epilepticus.
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persistent sodium channel actiVity mediates subthreshold membrane potential oscillations and low threshold spikes in rat entorhinal Cortex Layer V neurons
Neuroscience, 2001Co-Authors: N Agrawal, Bassam N Hamam, Jacopo Magistretti, Angel Alonso, David S RagsdaleAbstract:Abstract Entorhinal Cortex Layer V occupies a critical position in temporal lobe circuitry since, on the one hand, it serVes as the main conduit for the flow of information out of the hippocampal formation back to the neoCortex and, on the other, it closes a hippocampal–entorhinal loop by projecting upon the superficial cell Layers that giVe rise to the perforant path. Recent in Vitro electrophysiological studies haVe shown that rat entorhinal Cortex Layer V cells are endowed with the ability to generate subthreshold oscillations and all-or-none, low-threshold depolarizing potentials. In the present study, by applying current-clamp, Voltage-clamp and single-channel recording techniques in rat slices and dissociated neurons, we inVestigated whether entorhinal Cortex Layer V cells express a persistent sodium current and sustained sodium channel actiVity to eValuate the contribution of this actiVity to the subthreshold behaVior of the cells. Sharp-electrode recording in slices demonstrated that Layer V cells display tetrodotoxin-sensitiVe inward rectification in the depolarizing direction, suggesting that a persistent sodium current is present in the cells. Subthreshold oscillations and low-threshold regeneratiVe eVents were also abolished by tetrodotoxin, suggesting that their generation also requires the actiVation of such a low-threshold sodium current. The presence of a persistent sodium current was confirmed in whole-cell Voltage-clamp experiments, which reVealed that its actiVation “threshold” was negatiVe by about 10 mV to that of the transient sodium current. Furthermore, stationary noise analysis and cell-attached, patch-clamp recordings indicated that whole-cell persistent sodium currents were mediated by persistent sodium channel actiVity, consisting of relatiVely high-conductance (∼18 pS) sustained openings. The presence of a persistent sodium current in entorhinal Cortex Layer V cells can cause the generation of oscillatory behaVior, bursting actiVity and sustained discharge; this might be implicated in the encoding of memories in which the entorhinal Cortex participates but, under pathological situations, may also contribute to epileptogenesis and neurodegeneration.
Angel Alonso - One of the best experts on this subject based on the ideXlab platform.
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mechanism of graded persistent cellular actiVity of entorhinal Cortex Layer V neurons
Neuron, 2006Co-Authors: Erik Fransen, Alexei V. Egorov, Babak Tahvildari, Michael E Hasselmo, Angel AlonsoAbstract:Working memory is an emergent property of neuronal networks, but its cellular basis remains elusiVe. Recent data show that principal neurons of the entorhinal Cortex display persistent firing at graded firing rates that can be shifted up or down in response to brief excitatory or inhibitory stimuli. Here, we present a model of a potential mechanism for graded firing. Our multicompartmental model proVides stable plateau firing generated by a nonspecific calcium-sensitiVe cationic (CAN) current. Sustained firing is insensitiVe to small Variations in Ca2+ concentration in a neutral zone. HoweVer, both high and low Ca2+ leVels alter firing rates. Specifically, increases in persistent firing rate are triggered only during high leVels of calcium, while decreases in rate occur in the presence of low leVels of calcium. The model is consistent with detailed experimental obserVations and proVides a mechanism for maintenance of memory-related actiVity in indiVidual neurons.
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increased persistent sodium currents in rat entorhinal Cortex Layer V neurons in a post status epilepticus model of temporal lobe epilepsy
Epilepsia, 2003Co-Authors: N Agrawal, Angel Alonso, David S RagsdaleAbstract:Summary: Purpose: Spontaneous seizures in rats emerge seVeral weeks after induction of status epilepticus with pharmacologic treatment or electrical stimulation, proViding an animal model for human temporal lobe epilepsy. In this study, we inVestigated whether status epilepticus caused changes in the function of Voltage-gated sodium channels in entorhinal Cortex Layer V neurons, a cellular group important for the genesis of limbic seizures. Methods: We induced status epilepticus in rats, by using lithium-pilocarpine, and then 2–12 weeks later, used whole-cell Voltage-clamp to examine Voltage-actiVated sodium currents of acutely dissociated Layer V neurons. Results: Transient sodium currents of entorhinal Cortex Layer V neurons isolated from 9- to 12-week post–status epilepticus rats were similar to currents in age-matched controls; howeVer, low-threshold persistent sodium currents were significantly larger. This increase in persistent actiVity was not seen 2–3 weeks after pilocarpine treatment; thus it occurred after a delay comparable to the delay in the appearance of spontaneous seizures. Conclusions: Increased persistent currents are expected to accentuate neuronal excitability and thus may contribute to the genesis of spontaneous seizures after status epilepticus.
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Increased Persistent Sodium Currents in Rat Entorhinal Cortex Layer V Neurons in a Post–Status Epilepticus Model of Temporal Lobe Epilepsy
Epilepsia, 2003Co-Authors: N Agrawal, Angel Alonso, David S RagsdaleAbstract:Summary: Purpose: Spontaneous seizures in rats emerge seVeral weeks after induction of status epilepticus with pharmacologic treatment or electrical stimulation, proViding an animal model for human temporal lobe epilepsy. In this study, we inVestigated whether status epilepticus caused changes in the function of Voltage-gated sodium channels in entorhinal Cortex Layer V neurons, a cellular group important for the genesis of limbic seizures. Methods: We induced status epilepticus in rats, by using lithium-pilocarpine, and then 2–12 weeks later, used whole-cell Voltage-clamp to examine Voltage-actiVated sodium currents of acutely dissociated Layer V neurons. Results: Transient sodium currents of entorhinal Cortex Layer V neurons isolated from 9- to 12-week post–status epilepticus rats were similar to currents in age-matched controls; howeVer, low-threshold persistent sodium currents were significantly larger. This increase in persistent actiVity was not seen 2–3 weeks after pilocarpine treatment; thus it occurred after a delay comparable to the delay in the appearance of spontaneous seizures. Conclusions: Increased persistent currents are expected to accentuate neuronal excitability and thus may contribute to the genesis of spontaneous seizures after status epilepticus.
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Morphological and electrophysiological characteristics of Layer V neurons of the rat lateral entorhinal Cortex.
The Journal of comparative neurology, 2002Co-Authors: Bassam N Hamam, T E Kennedy, Angel Alonso, D G AmaralAbstract:The intrinsic electrophysiological and morphological properties of lateral entorhinal area (LEA) Layer V neurons were inVestigated by sharp electrode intracellular recording and biocytin labeling in Vitro. The morphological analysis reVealed that Layer V of the LEA contains three distinct subtypes of principal neurons, which were classified as pyramidal, horizontal, and polymorphic neurons. Pyramidal cells were the most abundant subtype (57%) and could be further subdiVided into neurons with large, small, and star-like somas. Similarly to pyramidal cells, horizontal neurons (11%) had a prominent apical dendrite. HoweVer, their distinctiVe basal dendritic plexus extended primarily in the horizontal plane. Polymorphic neurons (32%) were characterized by a multipolar dendritic organization. Electrophysiological analysis of neurons in the three categories demonstrated a diVersity of electrophysiological profiles within each category and no significant differences between groups. Neurons in the three subgroups could display instantaneous and/or time-dependent inward rectification and different degrees of spike frequency adaptation. None of the recorded cells displayed an intrinsic oscillatory bursting discharge. Many neurons in the three subgroups, howeVer, displayed slow (3.5-14 Hz), sustained, subthreshold membrane potential oscillations. The morphological and electrophysiological diVersity of principal neurons in the LEA parallels that preViously reported for the medial entorhinal area and suggests that, with respect to the deep Layers, similar information processing is performed across the mediolateral extent of the entorhinal Cortex. Layer V of the entorhinal Cortex may undertake Very complex operations beyond acting as a relay station of hippocampal processed information to the neoCortex.
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persistent sodium channel actiVity mediates subthreshold membrane potential oscillations and low threshold spikes in rat entorhinal Cortex Layer V neurons
Neuroscience, 2001Co-Authors: N Agrawal, Bassam N Hamam, Jacopo Magistretti, Angel Alonso, David S RagsdaleAbstract:Abstract Entorhinal Cortex Layer V occupies a critical position in temporal lobe circuitry since, on the one hand, it serVes as the main conduit for the flow of information out of the hippocampal formation back to the neoCortex and, on the other, it closes a hippocampal–entorhinal loop by projecting upon the superficial cell Layers that giVe rise to the perforant path. Recent in Vitro electrophysiological studies haVe shown that rat entorhinal Cortex Layer V cells are endowed with the ability to generate subthreshold oscillations and all-or-none, low-threshold depolarizing potentials. In the present study, by applying current-clamp, Voltage-clamp and single-channel recording techniques in rat slices and dissociated neurons, we inVestigated whether entorhinal Cortex Layer V cells express a persistent sodium current and sustained sodium channel actiVity to eValuate the contribution of this actiVity to the subthreshold behaVior of the cells. Sharp-electrode recording in slices demonstrated that Layer V cells display tetrodotoxin-sensitiVe inward rectification in the depolarizing direction, suggesting that a persistent sodium current is present in the cells. Subthreshold oscillations and low-threshold regeneratiVe eVents were also abolished by tetrodotoxin, suggesting that their generation also requires the actiVation of such a low-threshold sodium current. The presence of a persistent sodium current was confirmed in whole-cell Voltage-clamp experiments, which reVealed that its actiVation “threshold” was negatiVe by about 10 mV to that of the transient sodium current. Furthermore, stationary noise analysis and cell-attached, patch-clamp recordings indicated that whole-cell persistent sodium currents were mediated by persistent sodium channel actiVity, consisting of relatiVely high-conductance (∼18 pS) sustained openings. The presence of a persistent sodium current in entorhinal Cortex Layer V cells can cause the generation of oscillatory behaVior, bursting actiVity and sustained discharge; this might be implicated in the encoding of memories in which the entorhinal Cortex participates but, under pathological situations, may also contribute to epileptogenesis and neurodegeneration.
Alexei V. Egorov - One of the best experts on this subject based on the ideXlab platform.
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Processing of hippocampal network actiVity in the receiVer network of the medial entorhinal Cortex Layer V.
The Journal of Neuroscience, 2020Co-Authors: Andrei Rozov, Märt Rannap, Franziska Lorenz, Azat Nasretdinov, Andreas Draguhn, Alexei V. EgorovAbstract:The interplay between hippocampus and medial entorhinal Cortex (mEC) is of key importance for forming spatial representations. Within the hippocampal-entorhinal loop, the hippocampus receiVes context-specific signals from Layers II/III of the mEC and feeds memory-associated actiVity back into Layer V (LV). The processing of this output signal within the mEC, howeVer, is largely unknown. We characterized the actiVation of the receiVing mEC network by eVoked and naturally occurring output patterns in mouse hippocampal-entorhinal Cortex slices. Both types of glutamatergic neurons (mEC LVa and LVb) as well as fast-spiking inhibitory interneurons receiVe direct excitatory input from the intermediate/Ventral hippocampus. Connections between the two types of excitatory neurons are sparse, and local processing of hippocampal output signals within mEC LV is asymmetric, faVoring excitation of far projecting LVa neurons oVer locally projecting LVb neurons. These findings suggest a new role for mEC LV as a bifurcation gate for feedforward (telencephalic) and feedback (entorhinal-hippocampal) signal propagation.STATEMENT OF SIGNIFICANCEPatterned network actiVity in hippocampal networks plays a key role in the formation and consolidation of spatial memories. It is, howeVer, largely unclear how information is transferred to the neoCortex for long-term engrams. Here, we elucidate the propagation of network actiVity from the hippocampus to the medial entorhinal Cortex. We show that patterned output from the hippocampus reaches both major cell types of deep entorhinal Layers. These cells are, howeVer, only weakly connected, giVing rise to two parallel streams of actiVity for local and remote signal propagation, respectiVely. The relatiVe weight of both pathways is regulated by local inhibitory interneurons. Our data reVeal important insights into the hippocampal-neocortical dialogue which is of key importance for memory consolidation in the mammalian brain.
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downstream effects of hippocampal sharp waVe ripple oscillations on medial entorhinal Cortex Layer V neurons in Vitro
Hippocampus, 2016Co-Authors: Fabian C Roth, Andreas Draguhn, Katinka M Beyer, Martin Both, Alexei V. EgorovAbstract:The entorhinal Cortex (EC) is a critical component of the medial temporal lobe (MTL) memory system. Local networks within the MTL express a Variety of state-dependent network oscillations that are belieVed to organize neuronal actiVity during memory formation. The peculiar pattern of sharp waVe-ripple complexes (SPW-R) entrains neurons by a Very fast oscillation at ∼200 Hz in the hippocampal areas CA3 and CA1 and then propagates through the "output loop" into the EC. The precise mechanisms of SPW-R propagation and the resulting cellular input patterns in the mEC are, howeVer, largely unknown. We therefore inVestigated the actiVity of Layer V (LV) principal neurons of the medial EC (mEC) during SPW-R oscillations in horizontal mouse brain slices. Intracellular recordings in the mEC were combined with extracellular monitoring of propagating network actiVity. SPW-R in CA1 were regularly followed by negatiVe field potential deflections in the mEC. Propagation of SPW-R actiVity from CA1 to the mEC was mostly monosynaptic and excitatory, such that synaptic input to mEC LV neurons directly reflected unit actiVity in CA1. Comparison with propagating network actiVity from CA3 to CA1 reVealed a similar role of excitatory long-range connections for both regions. HoweVer, SPW-R-induced actiVity in CA1 inVolVed strong recruitment of rhythmic synaptic inhibition and corresponding fast field oscillations, in contrast to the mEC. These differences between features of propagating SPW-R emphasize the differential processing of network actiVity by each local network of the hippocampal output loop. © 2016 Wiley Periodicals, Inc.
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mechanism of graded persistent cellular actiVity of entorhinal Cortex Layer V neurons
Neuron, 2006Co-Authors: Erik Fransen, Alexei V. Egorov, Babak Tahvildari, Michael E Hasselmo, Angel AlonsoAbstract:Working memory is an emergent property of neuronal networks, but its cellular basis remains elusiVe. Recent data show that principal neurons of the entorhinal Cortex display persistent firing at graded firing rates that can be shifted up or down in response to brief excitatory or inhibitory stimuli. Here, we present a model of a potential mechanism for graded firing. Our multicompartmental model proVides stable plateau firing generated by a nonspecific calcium-sensitiVe cationic (CAN) current. Sustained firing is insensitiVe to small Variations in Ca2+ concentration in a neutral zone. HoweVer, both high and low Ca2+ leVels alter firing rates. Specifically, increases in persistent firing rate are triggered only during high leVels of calcium, while decreases in rate occur in the presence of low leVels of calcium. The model is consistent with detailed experimental obserVations and proVides a mechanism for maintenance of memory-related actiVity in indiVidual neurons.
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Ca2+-independent muscarinic excitation of rat medial entorhinal Cortex Layer V neurons.
The European journal of neuroscience, 2003Co-Authors: Alexei V. Egorov, Plamena R. Angelova, Uwe Heinemann, Wolfgang MüllerAbstract:Cholinergic actiVation of entorhinal Cortex (EC) Layer V neurons plays a crucial role in the medial temporal lobe memory system and in the pathophysiology of temporal lobe epilepsy. Here, we demonstrate that muscarinic actiVation by focal application of carbachol depolarizes EC Layer V neurons and induces epileptiform actiVity in rat brain slices. These seizure-like bursts are associated with a somatic [Ca 2 + ] i increase of 293 ′ 82 nM and are blocked by the glutamate receptor antagonists CNQX and APV Muscarinic actiVation did not directly eVoke a [Ca 2 + ] i increase, but subthreshold and suprathreshold depolarization did. Functional axon mapping reVealed local axon branching as well as axon collaterals ascending to Layers II and III. During blockade of ionotropic glutamatergic AMPA and NMDA receptors, carbachol depolarized Layer V neurons by +7.5 ′ 3.4 mV. This direct muscarinic depolarization was associated with a conductance increase of 35 ′ 10.3% (+4.3 ′ 1.25 nS). Intracellular buffering of [Ca 2 + ] i changes did not block this depolarization, but prolonged action potential duration and reduced adaptation of action potential firing. The muscarinic depolarization was neither blocked by combining intracellular Ca 2 + -buffering (EGTA or BAPTA) with non-specific Ca 2 + -channel inhibition by Ni + (1 mM), nor by Ba 2 + (1 mM) nor during inhibition of the h-current by 2 mM Cs + . In whole-cell patch-clamp recording, reVersal of the muscarinic current occurred at about -45 mV and -5 mV with complete substitution of intrapipette K + with Cs + . Thus, muscarinic depolarization of EC Layer V neurons appears to be primarily mediated by Ca 2 + -independent actiVation of non-specific cation channels that conduct K + about three times as well as Na + .
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Differential excitability and Voltage-dependent Ca2+ signalling in two types of medial entorhinal Cortex Layer V neurons.
The European journal of neuroscience, 2002Co-Authors: Alexei V. Egorov, Uwe Heinemann, Wolfgang MüllerAbstract:The entorhinal Cortex (EC) is a key structure in memory formation, relaying sensory information to the hippocampal formation and processed information to the neoCortex. EC neurons in the deep Layers modulate the transfer of sensory information by the superficial Layers and the dentate gyrus, and form the output to the neoCortex. Here we characterize two types of EC Layer V neurons by their fluorescence morphology, electrophysiology and intracellular Ca 2 + signalling using intracellular recording and Ca 2 + imaging. Pyramidal neurons show, in response to depolarizing current pulses, regular firing with strong adaptation and a fast and medium afterhyperpolarization (AHP) which are separated by a depolarizing notch and, with hyperpolarizing current injection, a transient sag. Multipolar cells respond to depolarization with delayed firing with Very weak adaptation and haVe no depolarizing notch between fast and medium AHP and no sag with hyperpolarization. The delayed firing was blocked by 30 μM 4-aminopyridine, indicating mediation by the D-type potassium current. Subthreshold depolarization eVoked membrane potential oscillations of 2-5 Hz in both cell types and an increase in [Ca 2 + ] i of 37 nM in pyramidal and 59 nM in multipolar neurons. RepetitiVe firing at 10 Hz for 30 s increased [Ca 2 + ] i in pyramidal and multipolar neurons by 194 and 295 nM, respectiVely. Differential temporal firing and Ca 2 + signalling suggest specific information processing and synaptic memory storage possibilities in these two Layer V cell types of the EC.
Wolfgang Müller - One of the best experts on this subject based on the ideXlab platform.
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Ca2+-independent muscarinic excitation of rat medial entorhinal Cortex Layer V neurons.
The European journal of neuroscience, 2003Co-Authors: Alexei V. Egorov, Plamena R. Angelova, Uwe Heinemann, Wolfgang MüllerAbstract:Cholinergic actiVation of entorhinal Cortex (EC) Layer V neurons plays a crucial role in the medial temporal lobe memory system and in the pathophysiology of temporal lobe epilepsy. Here, we demonstrate that muscarinic actiVation by focal application of carbachol depolarizes EC Layer V neurons and induces epileptiform actiVity in rat brain slices. These seizure-like bursts are associated with a somatic [Ca 2 + ] i increase of 293 ′ 82 nM and are blocked by the glutamate receptor antagonists CNQX and APV Muscarinic actiVation did not directly eVoke a [Ca 2 + ] i increase, but subthreshold and suprathreshold depolarization did. Functional axon mapping reVealed local axon branching as well as axon collaterals ascending to Layers II and III. During blockade of ionotropic glutamatergic AMPA and NMDA receptors, carbachol depolarized Layer V neurons by +7.5 ′ 3.4 mV. This direct muscarinic depolarization was associated with a conductance increase of 35 ′ 10.3% (+4.3 ′ 1.25 nS). Intracellular buffering of [Ca 2 + ] i changes did not block this depolarization, but prolonged action potential duration and reduced adaptation of action potential firing. The muscarinic depolarization was neither blocked by combining intracellular Ca 2 + -buffering (EGTA or BAPTA) with non-specific Ca 2 + -channel inhibition by Ni + (1 mM), nor by Ba 2 + (1 mM) nor during inhibition of the h-current by 2 mM Cs + . In whole-cell patch-clamp recording, reVersal of the muscarinic current occurred at about -45 mV and -5 mV with complete substitution of intrapipette K + with Cs + . Thus, muscarinic depolarization of EC Layer V neurons appears to be primarily mediated by Ca 2 + -independent actiVation of non-specific cation channels that conduct K + about three times as well as Na + .
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Differential excitability and Voltage-dependent Ca2+ signalling in two types of medial entorhinal Cortex Layer V neurons.
The European journal of neuroscience, 2002Co-Authors: Alexei V. Egorov, Uwe Heinemann, Wolfgang MüllerAbstract:The entorhinal Cortex (EC) is a key structure in memory formation, relaying sensory information to the hippocampal formation and processed information to the neoCortex. EC neurons in the deep Layers modulate the transfer of sensory information by the superficial Layers and the dentate gyrus, and form the output to the neoCortex. Here we characterize two types of EC Layer V neurons by their fluorescence morphology, electrophysiology and intracellular Ca 2 + signalling using intracellular recording and Ca 2 + imaging. Pyramidal neurons show, in response to depolarizing current pulses, regular firing with strong adaptation and a fast and medium afterhyperpolarization (AHP) which are separated by a depolarizing notch and, with hyperpolarizing current injection, a transient sag. Multipolar cells respond to depolarization with delayed firing with Very weak adaptation and haVe no depolarizing notch between fast and medium AHP and no sag with hyperpolarization. The delayed firing was blocked by 30 μM 4-aminopyridine, indicating mediation by the D-type potassium current. Subthreshold depolarization eVoked membrane potential oscillations of 2-5 Hz in both cell types and an increase in [Ca 2 + ] i of 37 nM in pyramidal and 59 nM in multipolar neurons. RepetitiVe firing at 10 Hz for 30 s increased [Ca 2 + ] i in pyramidal and multipolar neurons by 194 and 295 nM, respectiVely. Differential temporal firing and Ca 2 + signalling suggest specific information processing and synaptic memory storage possibilities in these two Layer V cell types of the EC.
