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Jacopo Magistretti - One of the best experts on this subject based on the ideXlab platform.
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two distinct types of depolarizing afterpotentials are differentially expressed in stellate and pyramidal like neurons of entorhinal Cortex Layer II
Hippocampus, 2016Co-Authors: Camilla Alessi, Alessandra Raspanti, Jacopo MagistrettiAbstract:Two types of principal neurons, stellate cells and pyramidal-like cells, are found in medial entorhinal-Cortex (mEC) Layer II, and are believed to represent two distinct channels of information processing and transmission in the entorhinal Cortex–hippocampus network. In this study, we found that depolarizing afterpotentials (DAPs) that follow single action potentials (APs) evoked from various levels of holding membrane voltage (Vh) show distinct properties in the two cells types. In both, an evident DAP followed the AP at near-threshold Vh levels, and was accompanied by an enhancement of excitability and spike-timing precision. This DAP was sensitive to voltage-gated Na+-channel block with TTx, but not to partial removal of extracellular Ca2+. Application of 5-μM anandamide, which inhibited the resurgent and persistent Na+-current components in a relatively selective way, significantly reduced the amplitude of this particular DAP while exerting poor effects on the foregoing AP. In the presence of background hyperpolarization, DAPs showed an opposite behavior in the two cell types, as in stellate cells they became even more prominent, whereas in pyramidal-like cells their amplitude was markedly reduced. The DAP observed in stellate cells under this condition was strongly inhibited by partial extracellular-Ca2+ removal, and was sensitive to the low-voltage-activated Ca2+-channel blocker, NNC55-0396. This Ca2+ dependence was not observed in the residual DAP evoked in pyramidal-like cells from likewise negative Vh levels. These results demonstrate that two distinct mechanism of DAP generation operate in mEC Layer-II neurons, one Na+-dependent and active at near-threshold Vh levels in both stellate and-pyramidal-like cells, the other Ca2+-dependent and only expressed by stellate cells in the presence of background membrane hyperpolarization. © 2015 Wiley Periodicals, Inc.
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distinct developmental patterns in the expression of transient persistent and resurgent na currents in entorhinal Cortex Layer II neurons
Brain Research, 2012Co-Authors: Maximiliano Jose Nigro, Giulia Quattrocolo, Jacopo MagistrettiAbstract:Abstract Sub- and near-threshold voltage-dependent Na+ currents (VDSCs) are of major importance in determining the electrical properties of medial entorhinal Cortex (mEC) Layer-II neurons. Developmental changes in the ability of mEC Layer-II stellate cells (SCs) to generate Na+-dependent, subthreshold electrical events have been reported between P14 and P18. In this study we examined the modifications occurring in the various components of VDSCs during postnatal development of mEC SCs. The transient, resurgent, and persistent Na+ currents (INaT, INaR, and INaP, respectively) showed distinct patterns of developmental expression in the time window considered (P5 to P24–27). All three currents prominently and steeply increased in absolute amplitude and conductance from P5 to at least P16. However, capacitive charge accumulation, an index of membrane surface area, also markedly increased in the same time window, and in the case of INaT the specific conductance per unit of accumulated capacitive charge remained relatively constant. By contrast, specific INaR and INaP conductances showed a significant tendency to increase, especially from P5 to P18. Neither INaR nor INaP represented a constant fraction of the total Na+ current at all developmental ages. Indeed, detectable levels of INaR and INaP were present in only ~ 20% and ~ 70%, respectively, of the cells on P5, and were observed in all cells only from P10 onwards. Moreover, the average INaR-to-INaT conductance ratio increased steadily from ~ 0.004 (P5) up to a plateau level of ~ 0.05 (P22+), whereas the INaP-to-INaT conductance ratio increased only from ~ 0.009 on P5 to ~ 0.02 on P22+. The relative increase in conductance ratio from P5 to P22 was significantly greater for INaR than for INaP, indicating that INaR expression starts later than that of INaP. These findings show that in mEC Layer-II SCs the single functional components of the VDSC are regulated differentially from each other as far as their developmental expression is concerned.
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Distinct developmental patterns in the expression of transient, persistent, and resurgent Na+ currents in entorhinal Cortex Layer-II neurons
Brain Research, 2012Co-Authors: Maximiliano Jose Nigro, Giulia Quattrocolo, Jacopo MagistrettiAbstract:Abstract Sub- and near-threshold voltage-dependent Na+ currents (VDSCs) are of major importance in determining the electrical properties of medial entorhinal Cortex (mEC) Layer-II neurons. Developmental changes in the ability of mEC Layer-II stellate cells (SCs) to generate Na+-dependent, subthreshold electrical events have been reported between P14 and P18. In this study we examined the modifications occurring in the various components of VDSCs during postnatal development of mEC SCs. The transient, resurgent, and persistent Na+ currents (INaT, INaR, and INaP, respectively) showed distinct patterns of developmental expression in the time window considered (P5 to P24–27). All three currents prominently and steeply increased in absolute amplitude and conductance from P5 to at least P16. However, capacitive charge accumulation, an index of membrane surface area, also markedly increased in the same time window, and in the case of INaT the specific conductance per unit of accumulated capacitive charge remained relatively constant. By contrast, specific INaR and INaP conductances showed a significant tendency to increase, especially from P5 to P18. Neither INaR nor INaP represented a constant fraction of the total Na+ current at all developmental ages. Indeed, detectable levels of INaR and INaP were present in only ~ 20% and ~ 70%, respectively, of the cells on P5, and were observed in all cells only from P10 onwards. Moreover, the average INaR-to-INaT conductance ratio increased steadily from ~ 0.004 (P5) up to a plateau level of ~ 0.05 (P22+), whereas the INaP-to-INaT conductance ratio increased only from ~ 0.009 on P5 to ~ 0.02 on P22+. The relative increase in conductance ratio from P5 to P22 was significantly greater for INaR than for INaP, indicating that INaR expression starts later than that of INaP. These findings show that in mEC Layer-II SCs the single functional components of the VDSC are regulated differentially from each other as far as their developmental expression is concerned.
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high voltage activated ca2 currents show similar patterns of expression in stellate and pyramidal cells from rat entorhinal Cortex Layer II
Brain Research, 2006Co-Authors: Loretta Castelli, Jacopo MagistrettiAbstract:Abstract High-voltage-activated (HVA) Ca2+ currents were studied in acutely isolated neurons from rat entorhinal Cortex (EC) Layer II. Stellate and pyramidal cells, the two main neuronal types of this structure, were visually identified based on morphological criteria. HVA currents were recorded by applying the whole-cell, patch-clamp technique, using 5-mM Ba2+ as the charge carrier. In both neuronal types, the amplitude of total HVA Ba2+ currents (IBas) showed a significant tendency to increase with postnatal age in the time window considered [postnatal day 15 (P15) to P28–29]. At P20–P29, when IBa expression reached stable levels, IBa density per unit of membrane area was not different in stellate versus pyramidal cells. The same was also observed when Ca2+, instead of Ba2+, was used as the charge carrier. The pharmacological current subtypes composing total HVA currents were characterized using selective blockers. Again, no significant differences were found between stellate and pyramidal cells with respect to the total–current fractions attributable to specific pharmacological Ca2+ channel subtypes. In both cell types, ∼52–55% of total IBas was abolished by the L-type channel blocker, nifedipine (10 μM), ∼23–30% by the N-type channel blocker, ω-conotoxin GVIA (1 μM), ∼22–24% by the P/Q-type channel blocker, ω-agatoxin IVA (100 nM), and ∼11–13% remained unblocked (R-type current) after simultaneous application of L-, N-, and P/Q-type channel blockers. The Cav 2.3 (α1E) channel blocker, SNX-482 (100 nM), abolished ∼57–62% of total R-type current. We conclude that HVA Ca2+ currents are expressed according to similar patterns in the somata and proximal dendrites of stellate and pyramidal cells of rat EC Layer II.
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spike patterning by ca2 dependent regulation of a muscarinic cation current in entorhinal Cortex Layer II neurons
Journal of Neurophysiology, 2004Co-Authors: Jacopo Magistretti, Ruby Klink, Mark H Shalinsky, Angel AlonsoAbstract:In entorhinal Cortex Layer II neurons, muscarinic receptor activation promotes depolarization via activation of a nonspecific cation current (INCM). Under muscarinic influence, these neurons also d...
Angel Alonso - One of the best experts on this subject based on the ideXlab platform.
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Ca2+‐dependent K+ currents and spike‐frequency adaptation in medial entorhinal Cortex Layer II stellate cells
Hippocampus, 2020Co-Authors: Farhan A Khawaja, Angel Alonso, Charles W BourqueAbstract:The entorhinal Cortex (EC), located in the medial temporal lobe (MTL) of the brain, plays an important functional role in the MTL memory circuit. Medial EC (MEC) Layer II stellate cells (SCs) serve as one of the most prominent target cell types within the EC for inputs arising from higher cortical areas, and these same cells provide most of the output from the EC to the hippocampal region. We used the whole-cell patch clamp technique in a rat in vitro slice preparation to test whether SCs express afterhyperpolarization (AHP) currents and if these currents can be modulated. Our results revealed that SCs contain medium (mIK(Ca)) and slow (sIAHP) Ca2+-dependent K+ currents. Furthermore, we determined that an apamin-sensitive current does not underlie the mAHP in SCs. Our studies also showed that a cAMP-dependent modulation process significantly reduces mIK(Ca), sIAHP, and spike-frequency adaptation in MEC Layer II SCs. Modulation of the firing pattern of SCs resulting from this effect may play an important role in the encoding of information related to memory processes. © 2007 Wiley-Liss, Inc.
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ca2 dependent k currents and spike frequency adaptation in medial entorhinal Cortex Layer II stellate cells
Hippocampus, 2007Co-Authors: Farhan A Khawaja, Angel Alonso, Charles W BourqueAbstract:The entorhinal Cortex (EC), located in the medial temporal lobe (MTL) of the brain, plays an important functional role in the MTL memory circuit. Medial EC (MEC) Layer II stellate cells (SCs) serve as one of the most prominent target cell types within the EC for inputs arising from higher cortical areas, and these same cells provide most of the output from the EC to the hippocampal region. We used the whole-cell patch clamp technique in a rat in vitro slice preparation to test whether SCs express afterhyperpolarization (AHP) currents and if these currents can be modulated. Our results revealed that SCs contain medium (mIK(Ca)) and slow (sIAHP) Ca2+-dependent K+ currents. Furthermore, we determined that an apamin-sensitive current does not underlie the mAHP in SCs. Our studies also showed that a cAMP-dependent modulation process significantly reduces mIK(Ca), sIAHP, and spike-frequency adaptation in MEC Layer II SCs. Modulation of the firing pattern of SCs resulting from this effect may play an important role in the encoding of information related to memory processes. © 2007 Wiley-Liss, Inc.
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spike patterning by ca2 dependent regulation of a muscarinic cation current in entorhinal Cortex Layer II neurons
Journal of Neurophysiology, 2004Co-Authors: Jacopo Magistretti, Ruby Klink, Mark H Shalinsky, Angel AlonsoAbstract:In entorhinal Cortex Layer II neurons, muscarinic receptor activation promotes depolarization via activation of a nonspecific cation current (INCM). Under muscarinic influence, these neurons also d...
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Fine Gating Properties of Channels Responsible for Persistent Sodium Current Generation in Entorhinal Cortex Neurons
The Journal of General Physiology, 2002Co-Authors: Jacopo Magistretti, Angel AlonsoAbstract:The gating properties of channels responsible for the generation of persistent Na+ current (INaP) in entorhinal Cortex Layer II principal neurons were investigated by performing cell-attached, patch-clamp experiments in acutely isolated cells. Voltage-gated Na+-channel activity was routinely elicited by applying 500-ms depolarizing test pulses positive to −60 mV from a holding potential of −100 mV. The channel activity underlying INaP consisted of prolonged and frequently delayed bursts during which repetitive openings were separated by short closings. The mean duration of openings within bursts was strongly voltage dependent, and increased by e times per every ∼12 mV of depolarization. On the other hand, intraburst closed times showed no major voltage dependence. The mean duration of burst events was also relatively voltage insensitive. The analysis of burst-duration frequency distribution returned two major, relatively voltage-independent time constants of ∼28 and ∼190 ms. The probability of burst openings to occur also appeared largely voltage independent. Because of the above “persistent” Na+-channel properties, the voltage dependence of the conductance underlying whole-cell INaP turned out to be largely the consequence of the pronounced voltage dependence of intraburst open times. On the other hand, some kinetic properties of the macroscopic INaP, and in particular the fast and intermediate INaP-decay components observed during step depolarizations, were found to largely reflect mean burst duration of the underlying channel openings. A further INaP decay process, namely slow inactivation, was paralleled instead by a progressive increase of interburst closed times during the application of long-lasting (i.e., 20 s) depolarizing pulses. In addition, long-lasting depolarizations also promoted a channel gating modality characterized by shorter burst durations than normally seen using 500-ms test pulses, with a predominant burst-duration time constant of ∼5–6 ms. The above data, therefore, provide a detailed picture of the single-channel bases of INaP voltage-dependent and kinetic properties in entorhinal Cortex Layer II neurons.
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muscarinic activation of a cation current and associated current noise in entorhinal Cortex Layer II neurons
Journal of Neurophysiology, 2002Co-Authors: Mark H Shalinsky, Jacopo Magistretti, Angel AlonsoAbstract:The effects of muscarinic stimulation on the membrane potential and current of in situ rat entorhinal-Cortex Layer-II principal neurons were analyzed using the whole cell, patch-clamp technique. In current-clamp experiments, application of carbachol (CCh) induced a slowly developing, prolonged depolarization initially accompanied by a slight decrease or no significant change in input resistance. By contrast, in a later phase of the depolarization input resistance appeared consistently increased. To elucidate the ionic bases of these effects, voltage-clamp experiments were then carried out. In recordings performed in nearly physiological ionic conditions at the holding potential of −60 mV, CCh application promoted the slow development of an inward current deflection consistently associated with a prominent increase in current noise. Similarly to voltage responses to CCh, this inward-current induction was abolished by the muscarinic antagonist, atropine. Current-voltage relationships derived by applying ramp voltage protocols during the different phases of the CCh-induced inward-current deflection revealed the early induction of an inward current that manifested a linear current/voltage relationship in the subthreshold range and the longer-lasting block of an outward K+ current. The latter current could be blocked by 1 mM extracellular Ba2+, which allowed us to study the CCh-induced inward current ( I CCh) in isolation. The extrapolated reversal potential of the isolated I CCh was ≈0 mV and was not modified by complete substitution of intrapipette K+ with Cs+. Moreover, the extrapolated I CCh reversal shifted to approximately −20 mV on removal of 50% extracellular Na+. These results are consistent with I CChbeing a nonspecific cation current. Finally, noise analysis of I CCh returned an estimated conductance of the underlying channels of ∼13.5 pS. We conclude that the depolarizing effect of muscarinic stimuli on entorhinal-Cortex Layer-II principal neurons depends on both the block of a K+ conductance and the activation of a “noisy” nonspecific cation current. We suggest that the membrane current fluctuations brought about by I CCh channel noise may facilitate the “theta” oscillatory dynamics of these neurons and enhance firing reliability and synchronization.
Maximiliano Jose Nigro - One of the best experts on this subject based on the ideXlab platform.
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physiological roles of kv2 channels in entorhinal Cortex Layer II stellate cells revealed by guangxitoxin 1e
The Journal of Physiology, 2017Co-Authors: Christoph Honigsperger, Maximiliano Jose Nigro, Johan F StormAbstract:Key points Kv2 channels underlie delayed-rectifier potassium currents in various neurons, although their physiological roles often remain elusive. Almost nothing is known about Kv2 channel functions in medial entorhinal Cortex (mEC) neurons, which are involved in representing space, memory formation, epilepsy and dementia. Stellate cells in Layer II of the mEC project to the hippocampus and are considered to be space-representing grid cells. We used the new Kv2 blocker Guangxitoxin-1E (GTx) to study Kv2 functions in these neurons. Voltage clamp recordings from mEC stellate cells in rat brain slices showed that GTx inhibited delayed-rectifier K+ current but not transient A-type current. In current clamp, GTx had multiple effects: (i) increasing excitability and bursting at moderate spike rates but reducing firing at high rates; (II) enhancing after-depolarizations; (IIi) reducing the fast and medium after-hyperpolarizations; (iv) broadening action potentials; and (v) reducing spike clustering. GTx is a useful tool for studying Kv2 channels and their functions in neurons. Abstract The medial entorhinal Cortex (mEC) is strongly involved in spatial navigation, memory, dementia and epilepsy. Although potassium channels shape neuronal activity, their roles in mEC are largely unknown. We used the new Kv2 blocker Guangxitoxin-1E (GTx; 10–100 nm) in rat brain slices to investigate Kv2 channel functions in mEC Layer II stellate cells (SCs). These neurons project to the hippocampus and are considered to be grid cells representing space. Voltage clamp recordings from SCs nucleated patches showed that GTx inhibited a delayed rectifier K+ current activating beyond –30 mV but not transient A-type current. In current clamp, GTx (i) had almost no effect on the first action potential but markedly slowed repolarization of late spikes during repetitive firing; (II) enhanced the after-depolarization (ADP); (IIi) reduced fast and medium after-hyperpolarizations (AHPs); (iv) strongly enhanced burst firing and increased excitability at moderate spike rates but reduced spiking at high rates; and (v) reduced spike clustering and rebound potentials. The changes in bursting and excitability were related to the altered ADPs and AHPs. Kv2 channels strongly shape the activity of mEC SCs by affecting spike repolarization, after-potentials, excitability and spike patterns. GTx is a useful tool and may serve to further clarify Kv2 channel functions in neurons. We conclude that Kv2 channels in mEC SCs are important determinants of intrinsic properties that allow these neurons to produce spatial representation. The results of the present study may also be important for the accurate modelling of grid cells.
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expression and functional roles of kv7 kcnq m channels in rat medial entorhinal Cortex Layer II stellate cells
The Journal of Neuroscience, 2014Co-Authors: Maximiliano Jose Nigro, Pedro Mateosaparicio, Johan F StormAbstract:The medial entorhinal Cortex (MEC) is important for spatial navigation and memory. Stellate cells (SCs) of MEC Layer II provide major input to the hippocampus, and are thought to be the neuronal correlate of the grid cells. Their electrophysiological properties have been used to explain grid field formation. However, little is known about the functional roles of potassium channels in SCs. M-current is a slowly activating potassium current, active at subthreshold potentials. Although some studies have suggested that Kv7/M-channels may affect subthreshold resonance in SCs, others have found no Kv7/M-current in these cells, so the expression and roles of Kv7/M-channels in SCs are still debated. Using whole-cell voltage-clamp, we have identified a typical M-current with pharmacological properties characteristic of Kv7/M-channels in rat MEC SCs. Current-clamp experiments showed that the specific Kv7/M-channel blocker XE991 increased SCs excitability, and reduced spike frequency adaptation. Our results demonstrate that Kv7/M-channels are expressed in SCs and contribute substantially to regulation of excitability in these cells.
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Expression and Functional Roles of Kv7/KCNQ/M-Channels in Rat Medial Entorhinal Cortex Layer II Stellate Cells
The Journal of Neuroscience, 2014Co-Authors: Maximiliano Jose Nigro, Pedro Mateos-aparicio, Johan F StormAbstract:The medial entorhinal Cortex (MEC) is important for spatial navigation and memory. Stellate cells (SCs) of MEC Layer II provide major input to the hippocampus, and are thought to be the neuronal correlate of the grid cells. Their electrophysiological properties have been used to explain grid field formation. However, little is known about the functional roles of potassium channels in SCs. M-current is a slowly activating potassium current, active at subthreshold potentials. Although some studies have suggested that Kv7/M-channels may affect subthreshold resonance in SCs, others have found no Kv7/M-current in these cells, so the expression and roles of Kv7/M-channels in SCs are still debated. Using whole-cell voltage-clamp, we have identified a typical M-current with pharmacological properties characteristic of Kv7/M-channels in rat MEC SCs. Current-clamp experiments showed that the specific Kv7/M-channel blocker XE991 increased SCs excitability, and reduced spike frequency adaptation. Our results demonstrate that Kv7/M-channels are expressed in SCs and contribute substantially to regulation of excitability in these cells.
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distinct developmental patterns in the expression of transient persistent and resurgent na currents in entorhinal Cortex Layer II neurons
Brain Research, 2012Co-Authors: Maximiliano Jose Nigro, Giulia Quattrocolo, Jacopo MagistrettiAbstract:Abstract Sub- and near-threshold voltage-dependent Na+ currents (VDSCs) are of major importance in determining the electrical properties of medial entorhinal Cortex (mEC) Layer-II neurons. Developmental changes in the ability of mEC Layer-II stellate cells (SCs) to generate Na+-dependent, subthreshold electrical events have been reported between P14 and P18. In this study we examined the modifications occurring in the various components of VDSCs during postnatal development of mEC SCs. The transient, resurgent, and persistent Na+ currents (INaT, INaR, and INaP, respectively) showed distinct patterns of developmental expression in the time window considered (P5 to P24–27). All three currents prominently and steeply increased in absolute amplitude and conductance from P5 to at least P16. However, capacitive charge accumulation, an index of membrane surface area, also markedly increased in the same time window, and in the case of INaT the specific conductance per unit of accumulated capacitive charge remained relatively constant. By contrast, specific INaR and INaP conductances showed a significant tendency to increase, especially from P5 to P18. Neither INaR nor INaP represented a constant fraction of the total Na+ current at all developmental ages. Indeed, detectable levels of INaR and INaP were present in only ~ 20% and ~ 70%, respectively, of the cells on P5, and were observed in all cells only from P10 onwards. Moreover, the average INaR-to-INaT conductance ratio increased steadily from ~ 0.004 (P5) up to a plateau level of ~ 0.05 (P22+), whereas the INaP-to-INaT conductance ratio increased only from ~ 0.009 on P5 to ~ 0.02 on P22+. The relative increase in conductance ratio from P5 to P22 was significantly greater for INaR than for INaP, indicating that INaR expression starts later than that of INaP. These findings show that in mEC Layer-II SCs the single functional components of the VDSC are regulated differentially from each other as far as their developmental expression is concerned.
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Distinct developmental patterns in the expression of transient, persistent, and resurgent Na+ currents in entorhinal Cortex Layer-II neurons
Brain Research, 2012Co-Authors: Maximiliano Jose Nigro, Giulia Quattrocolo, Jacopo MagistrettiAbstract:Abstract Sub- and near-threshold voltage-dependent Na+ currents (VDSCs) are of major importance in determining the electrical properties of medial entorhinal Cortex (mEC) Layer-II neurons. Developmental changes in the ability of mEC Layer-II stellate cells (SCs) to generate Na+-dependent, subthreshold electrical events have been reported between P14 and P18. In this study we examined the modifications occurring in the various components of VDSCs during postnatal development of mEC SCs. The transient, resurgent, and persistent Na+ currents (INaT, INaR, and INaP, respectively) showed distinct patterns of developmental expression in the time window considered (P5 to P24–27). All three currents prominently and steeply increased in absolute amplitude and conductance from P5 to at least P16. However, capacitive charge accumulation, an index of membrane surface area, also markedly increased in the same time window, and in the case of INaT the specific conductance per unit of accumulated capacitive charge remained relatively constant. By contrast, specific INaR and INaP conductances showed a significant tendency to increase, especially from P5 to P18. Neither INaR nor INaP represented a constant fraction of the total Na+ current at all developmental ages. Indeed, detectable levels of INaR and INaP were present in only ~ 20% and ~ 70%, respectively, of the cells on P5, and were observed in all cells only from P10 onwards. Moreover, the average INaR-to-INaT conductance ratio increased steadily from ~ 0.004 (P5) up to a plateau level of ~ 0.05 (P22+), whereas the INaP-to-INaT conductance ratio increased only from ~ 0.009 on P5 to ~ 0.02 on P22+. The relative increase in conductance ratio from P5 to P22 was significantly greater for INaR than for INaP, indicating that INaR expression starts later than that of INaP. These findings show that in mEC Layer-II SCs the single functional components of the VDSC are regulated differentially from each other as far as their developmental expression is concerned.
A Alonso - One of the best experts on this subject based on the ideXlab platform.
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Direct demonstration of persistent Na+ channel activity in dendritic processes of mammalian cortical neurones.
The Journal of physiology, 1999Co-Authors: J Magistretti, D S Ragsdale, A AlonsoAbstract:1. Single Na+ channel activity was recorded in patch-clamp, cell-attached experiments performed on dendritic processes of acutely isolated principal neurones from rat entorhinal-Cortex Layer II. The distances of the recording sites from the soma ranged from approximately 20 to approximately 100 microm. 2. Step depolarisations from holding potentials of -120 to -100 mV to test potentials of -60 to +10 mV elicited Na+ channel openings in all of the recorded patches (n = 16). 3. In 10 patches, besides transient Na+ channel openings clustered within the first few milliseconds of the depolarising pulses, prolonged and/or late Na+ channel openings were also regularly observed. This 'persistent' Na+ channel activity produced net inward, persistent currents in ensemble-average traces, and remained stable over the entire duration of the experiments ( approximately 9 to 30 min). 4. Two of these patches contained < or = 3 channels. In these cases, persistent Na+ channel openings could be attributed to the activity of one single channel. 5. The voltage dependence of persistent-current amplitude in ensemble-average traces closely resembled that of whole-cell, persistent Na+ current expressed by the same neurones, and displayed the same characteristic low threshold of activation. 6. Dendritic, persistent Na+ channel openings had relatively high single-channel conductance ( approximately 20 pS), similar to what is observed for somatic, persistent Na+ channels. 7. We conclude that a stable, persistent Na+ channel activity is expressed by proximal dendrites of entorhinal-Cortex Layer II principal neurones, and can contribute a significant low-threshold, persistent Na+ current to the dendritic processing of excitatory synaptic inputs.
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differential electroresponsiveness of stellate and pyramidal like cells of medial entorhinal Cortex Layer II
Journal of Neurophysiology, 1993Co-Authors: A Alonso, R KlinkAbstract:1. The electroresponsive properties of neurons from Layer II of the rat medial entorhinal Cortex (MEC) were studied by intracellular recording under current clamp in an in vitro brain slice prepara...
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ionic mechanisms for the subthreshold oscillations and differential electroresponsiveness of medial entorhinal Cortex Layer II neurons
Journal of Neurophysiology, 1993Co-Authors: R Klink, A AlonsoAbstract:1. Layer II of the medial entorhinal Cortex is composed of two electrophysiologically and morphologically distinct types of projection neurons: stellate cells (SCs), which are distinguished by rhythmic subthreshold oscillatory activity, and non-SCs. The ionic mechanisms underlying their differential electroresponsiveness, particularly in the subthreshold range of membrane potentials, were investigated in an "in vitro" slice preparation. 2. In both SCs and non-SCs, the apparent membrane input resistance was markedly voltage dependent, respectively decreasing or increasing at hyperpolarized or subthreshold depolarized potential levels. Thus the neurons displayed inward rectification in the hyperpolarizing and depolarizing range. 3. In the depolarizing range, inward rectification was blocked by tetrodotoxin (TTX, 1 microM) in both types of neurons and thus shown to depend on the presence of a persistent low-threshold Na+ conductance (gNap). However, in the presence of TTX, pronounced outward rectification became manifest in the subthreshold depolarizing range of membrane potentials (positive to -60 mV) in the SCs but not in the non-SCs. 4. The rhythmic subthreshold membrane potential oscillations that were present only in the SCs were abolished by TTX and not by Ca2+ conductance block with Cd2+ or Co2+. Subthreshold oscillations thus rely on the activation of voltage-gated Na+, and not Ca2+, conductances. The Ca2+ conductance block also had no effect on the subthreshold outward rectification. 5. Prominent time-dependent inward rectification in the hyperpolarizing range in the SCs persisted after Na(+)- and Ca2+ conductance block. This rectification was not affected by Ba2+ (1 mM), but was blocked by Cs+ (1-4 mM). Therefore, it is most probably generated by a hyperpolarization-activated cationic current (Q-like current). However, the Q-like current appears to play no major role in the generation of subthreshold rhythmic membrane potential oscillations, because these persisted in the presence of Cs+. 6. On the other hand, in the SCs, the fast, sustained, outward rectification that strongly developed (after Na+ conductance block) at the oscillatory voltage level was not affected by Cs+ but was blocked by Ba2+ (1 mM). Barium was also effective in blocking the subthreshold membrane potential oscillations. 7. In the non-SCs, which do not generate subthreshold rhythmic membrane potential oscillations or manifest subthreshold outward rectification in TTX, Ca2+ conductance block abolished spike repolarization and caused the development of long-lasting Na(+)-dependent plateau potentials at a high suprathreshold voltage level. At this level, where prominent delayed rectification is present, the Na+ plateaus sustained rhythmic membrane potential oscillations.(ABSTRACT TRUNCATED AT 400 WORDS)
Uwe Heinemann - One of the best experts on this subject based on the ideXlab platform.
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contribution of near threshold currents to intrinsic oscillatory activity in rat medial entorhinal Cortex Layer II stellate cells
Journal of Neurophysiology, 2013Co-Authors: Anne Boehlen, Uwe Heinemann, Christian Henneberger, Irina ErchovaAbstract:The temporal lobe is well known for its oscillatory activity associated with exploration, navigation, and learning. Intrinsic membrane potential oscillations (MPOs) and resonance of stellate cells ...
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dynamics of rat entorhinal Cortex Layer II and IIi cells characteristics of membrane potential resonance at rest predict oscillation properties near threshold
The Journal of Physiology, 2004Co-Authors: Irina Erchova, Uwe Heinemann, G Kreck, Andreas V M HerzAbstract:Neurones generate intrinsic subthreshold membrane potential oscillations (MPOs) under various physiological and behavioural conditions. These oscillations influence neural responses and coding properties on many levels. On the single-cell level, MPOs modulate the temporal precision of action potentials; they also have a pronounced impact on large-scale cortical activity. Recent studies have described a close association between the MPOs of a given neurone and its electrical resonance properties. Using intracellular sharp microelectrode recordings we examine both dynamical characteristics in Layers II and III of the entorhinal Cortex (EC). Our data from EC Layer II stellate cells show strong membrane potential resonances and oscillations, both in the range of 5–15 Hz. At the resonance maximum, the membrane impedance can be more than twice as large as the input resistance. In EC Layer III cells, MPOs could not be elicited, and frequency-resolved impedances decay monotonically with increasing frequency or has only a small peak followed by a subsequent decay. To quantify and compare the resonance and oscillation properties, we use a simple mathematical model that includes stochastic components to capture channel noise. Based on this model we demonstrate that electrical resonance is closely related though not equivalent to the occurrence of sag-potentials and MPOs. MPO frequencies can be predicted from the membrane impedance curve for stellate cells. The model also explains the broad-band nature of the observed MPOs. This underscores the importance of intrinsic noise sources for subthreshold phenomena and rules out a deterministic description of MPOs. In addition, our results show that the two identified cell classes in the superficial EC Layers, which are known to target different areas in the hippocampus, also have different preferred frequency ranges and dynamic characteristics. Intrinsic cell properties may thus play a major role for the frequency-dependent information flow in the hippocampal formation.
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calcium currents in rat entorhinal Cortex Layer II stellate and Layer IIi pyramidal neurons in acute brain slice
Neuroscience Letters, 2002Co-Authors: Violeta Visan, Uwe Heinemann, Andriy Volynets, Wolfgang MullerAbstract:Abstract The entorhinal Cortex (EC) is an essential relay station in neocortical – hippocampal information transfer and memory functions. Layer II stellate and Layer III pyramidal neurons show specific damage in Alzheimer's disease and epilepsy, respectively. Using whole cell patch clamp recording in rat brain slices we here demonstrate that high voltage activated Ca 2+ -currents ( I Ca 2+ ) are about 1.6-fold bigger in stellate cells than in pyramidal neurons while current density is equal in both cell types. In stellate cells I Ca 2+ shows stronger inactivation with depolarization, block of I Ca 2+ by Ni 2+ (300 and 600 μM) is more effective, and this block decreases more for currents evoked from a less negative holding potential than in Layer III pyramidal neurons. These data indicate distinct molecular composition of Ca 2+ -channels and can partially explain stronger increases of [Ca 2+ ] i during 10 Hz firing activity in EC pyramidal versus stellate neurons.
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Subthreshold membrane potential oscillations in neurons of deep Layers of the entorhinal Cortex
Neuroscience, 1998Co-Authors: Dietmar Schmitz, Tengis Gloveli, Joachim Behr, Tamar Dugladze, Uwe HeinemannAbstract:Abstract Neuronal oscillations are important for information processing.6,17 The entorhinal Cortex is one of the structures which is involved in generation of theta rhythm.1,16 The major role of the entorhinal Cortex is to feed diverse sources of information both to and from the hippocampus.3,8,13 Far from simply being a funnel for this information it becomes clear that the entorhinal Cortex has its own active properties that contribute to signal processing.7,10 Interestingly, stellate cells in Layer II of the entorhinal Cortex can intrinsically generate subthreshold, Na+-dependent membrane potential oscillations.4,12 Here, using intracellular and patch-clamp recordings, we report a similar phenomenon from neurons of the deep Layers of the entorhinal Cortex. In our in vitro slice preparation about two-thirds of recorded neurons were able to generate voltage-sensitive subthreshold membrane potential oscillations. At a membrane potential of about −50 mV the mean frequency of the voltage-oscillations was 8.1 Hz, whereby at slightly more positive potentials (−44 mV) the frequency of the membrane potential oscillations was 20 Hz and the oscillations became interrupted by clusters of non-adapting trains of spikes. Pharmacological experiments revealed that the oscillations were not affected by Cs+, but could be blocked by the fast Na+-channel blocker tetrodotoxin. We therefore conclude that voltage- and Na+-dependent subthreshold membrane potential oscillations are not only present in stellate cells of entorhinal Cortex-Layer II, but are also typical for neurons of the deep Layers of the entorhinal Cortex.
