Loss of I A Expression and Increased Excitability in Postnatal Rat Cajal-Retzius Cells

1999 ◽  
Vol 82 (3) ◽  
pp. 1303-1310 ◽  
Author(s):  
Jean-Marc Mienville ◽  
Irina Maric ◽  
Dragan Maric ◽  
John R. Clay
Keyword(s):  
Cortical Neurons ◽  
Repetitive Firing ◽  
Na Channel ◽  
Cortical Function ◽  
Network Function ◽  
Rat Neocortex ◽  
K Current ◽  
Layer I ◽  
Retzius Cells

Although an important secretory function of Cajal-Retzius (CR) cells has been discovered recently, the precise electrical status of these cells among other layer I neurons in particular and in cortical function in general is still unclear. In this paper, early postnatal CR cells from rat neocortex were found to express an inactivating K current whose molecular substrate is likely to be the Kv1.4 channel. Both electrophysiological and immunocytochemical experiments revealed that expression of this A-type current is down-regulated in vivo and virtually disappears by the end of the second postnatal week. At this time, CR cells have become capable of evoked repetitive firing, and their action potentials are larger and faster, yet these electrical properties still appear incompatible with a role in cortical network function, as inferred from comparisons with other cortical neurons. Also at this time, a large proportion of CR cells display spontaneous spiking activity, which suggests the possibility of additional roles for these cells. We conclude that the loss of A channels along with an increase in Na channel density shape the changes in excitability of postnatal CR cells, in terms of both the patterns of evoked firing and the emergence of spontaneous spiking.

A calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons

1980 ◽  
Vol 43 (2) ◽  
pp. 409-419 ◽  
Author(s):  
J. R. Hotson ◽  
D. A. Prince
Keyword(s):  
Cortical Neurons ◽  
Hippocampal Neurons ◽  
Channel Blocker ◽  
Repetitive Firing ◽  
Na Channel ◽  
Molluscan Neurons ◽  
Potential Oscillations ◽  
Ca1 Neurons ◽  
K Current

1. A long-lasting afterhyperpolarization (AHP) follows current-induced repetitive firing in hippocampal CA1 neurons studied in vitro. A 10-25% increase in membrane slope conductance occurs during the AHP, suggesting that it may be mediated by an increased conductance to either K+ or Cl-. 2. Intracellular Cl- iontophoresis does not alter the AHP but does attenuate the IPSP. In contrast Ba2+, a cation that can decrease K+ conductance, eliminates the AHP but not the IPSP. These findings suggest the AHP is produced by a long-lasting increased conductance to K+, and is distinct from the IPSP. 3. Mn2+, a Ca2+-channel blocker, eliminates the AHP. In comparison, the AHP persists in the presence of the Na+-channel blocker, tetrodotoxin (TTX), and appears to be temporally associated with TTX-resistant "Ca2+ spikes." It is concluded that AHP is probably activated by Ca2+ influx. 4. These observations indicate that the AHP may be produced by a Ca2+ activated K+ current. A balance between cellular depolarization produced by Ca2+ entry and repolarization generated by a Ca2+-activated K+ current appears to operate to control excitability in some mammalian cortical neurons as it does in molluscan neurons. Disruption of this balance by Ba2+ produces spontaneous membrane-potential oscillations and recurrent burst firing in hippocampal neurons. Increases in the magnitude and duration of Ca2+ depolarization and/or decreases in the Ca2+-activated, K+-mediated repolarization may be mechanisms that lead to spontaneous, epileptiform bursting in mammalian cortical neurons.

scholarly journals Altered network properties in C9ORF72 repeat expansion cortical neurons are due to synaptic dysfunction

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Emma M. Perkins ◽  
Karen Burr ◽  
Poulomi Banerjee ◽  
Arpan R. Mehta ◽  
Owen Dando ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Vesicle ◽  
Cortical Neurons ◽  
Electrode Array ◽  
Repeat Expansion ◽  
Cortical Network ◽  
Synaptic Function ◽  
Network Activity ◽  
Cortical Function ◽  
Network Function

Abstract Background Physiological disturbances in cortical network excitability and plasticity are established and widespread in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients, including those harbouring the C9ORF72 repeat expansion (C9ORF72RE) mutation – the most common genetic impairment causal to ALS and FTD. Noting that perturbations in cortical function are evidenced pre-symptomatically, and that the cortex is associated with widespread pathology, cortical dysfunction is thought to be an early driver of neurodegenerative disease progression. However, our understanding of how altered network function manifests at the cellular and molecular level is not clear. Methods To address this we have generated cortical neurons from patient-derived iPSCs harbouring C9ORF72RE mutations, as well as from their isogenic expansion-corrected controls. We have established a model of network activity in these neurons using multi-electrode array electrophysiology. We have then mechanistically examined the physiological processes underpinning network dysfunction using a combination of patch-clamp electrophysiology, immunocytochemistry, pharmacology and transcriptomic profiling. Results We find that C9ORF72RE causes elevated network burst activity, associated with enhanced synaptic input, yet lower burst duration, attributable to impaired pre-synaptic vesicle dynamics. We also show that the C9ORF72RE is associated with impaired synaptic plasticity. Moreover, RNA-seq analysis revealed dysregulated molecular pathways impacting on synaptic function. All molecular, cellular and network deficits are rescued by CRISPR/Cas9 correction of C9ORF72RE. Our study provides a mechanistic view of the early dysregulated processes that underpin cortical network dysfunction in ALS-FTD. Conclusion These findings suggest synaptic pathophysiology is widespread in ALS-FTD and has an early and fundamental role in driving altered network function that is thought to contribute to neurodegenerative processes in these patients. The overall importance is the identification of previously unidentified defects in pre and postsynaptic compartments affecting synaptic plasticity, synaptic vesicle stores, and network propagation, which directly impact upon cortical function.

Abstract 202: Aging Alters the Electrical and Mechanical properties of LV Myocytes

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Andrea Sorrentino ◽  
Sergio Signore ◽  
Mark Sundman ◽  
Ramaswamy Kannappan ◽  
Chiara Mangiaracina ◽  
...  
Keyword(s):  
Mechanical Performance ◽  
Na Channel ◽  
Relaxation Phase ◽  
Qt Intervals ◽  
K Current ◽  
Electrocardiographic Parameters ◽  
Perfused Hearts ◽  
Old Mice ◽  
Ionic Basis

Aging results in delays in the electrical recovery of the heart, enhancing the risk of malignant ventricular arrhythmias and sudden death. But whether altered electrical properties affect myocardial mechanical performance remains unclear. The aim of this study was to establish the ionic basis for the protracted repolarization of the senescent heart, and to determine whether these electrical changes impact on myocardial contractility. For this purpose, electrophysiological analyses were conducted in vivo and in isolated LV myocyte preparations from mice ranging from 3 to 30 months of age. Electrocardiographic parameters were preserved from 3 to 12 months of age, whereas animals 2 years or older presented prolonged PR, QRS and QT intervals. These in vivo results were confirmed in the isolated organ, using Langendorff perfused hearts. Myocytes from 30 months old mice showed longer early and late repolarization phases of the action potential (AP), in comparison with cells from animals at 3 months. By voltage-clamp, the density of the transient outward K+ current (Ito) was significantly reduced in old, whereas the late Na+ current (INaL) was increased, changes consistent with the prolonged AP of old cells. Additionally, by Western blotting, the SCN1B subunit, involved in Na+ channel gating, was reduced with age. Using field stimulation, old myocytes presented slower Ca2+ transient decay and relaxation, in comparison to young. Blockade of INaL with mexiletine in old myocytes shortened the AP duration, and fastened the decay of Ca2+ transients and relaxation. To assess the functional impact of INaL on the myocardium, papillary muscles were studied in an isometric system. Using tension-length protocols, old muscles presented elevated diastolic tension with respect to young. Importantly, inhibition of INaL in old muscles reduced diastolic tension, and attenuated the active developed force. Conversely, increasing INaL in the myocardium of young mice with anemonetoxin had opposite effects. Overall, these data indicate that aging results in a prolongation of the AP mediated, at least in part, by enhanced INaL. The prolonged repolarization of the AP contributes to the slower clearance of diastolic Ca2+ from the cytoplasm, resulting in protracted relaxation phase.

scholarly journals Selective attenuation of Ether-a-go-go related K+ currents by endogenous acetylcholine reduces spike-frequency adaptation and network correlation

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Edward D Cui ◽  
Ben W Strowbridge
Keyword(s):  
Late Phase ◽  
Pyramidal Cells ◽  
Spike Frequency ◽  
Spike Frequency Adaptation ◽  
Firing Rates ◽  
Frequency Adaptation ◽  
Rat Neocortex ◽  
Persistent Firing ◽  
K Current

Most neurons do not simply convert inputs into firing rates. Instead, moment-to-moment firing rates reflect interactions between synaptic inputs and intrinsic currents. Few studies investigated how intrinsic currents function together to modulate output discharges and which of the currents attenuated by synthetic cholinergic ligands are actually modulated by endogenous acetylcholine (ACh). In this study we optogenetically stimulated cholinergic fibers in rat neocortex and find that ACh enhances excitability by reducing Ether-à-go-go Related Gene (ERG) K+ current. We find ERG mediates the late phase of spike-frequency adaptation in pyramidal cells and is recruited later than both SK and M currents. Attenuation of ERG during coincident depolarization and ACh release leads to reduced late phase spike-frequency adaptation and persistent firing. In neuronal ensembles, attenuating ERG enhanced signal-to-noise ratios and reduced signal correlation, suggesting that these two hallmarks of cholinergic function in vivo may result from modulation of intrinsic properties.

scholarly journals Network activity influences the subthreshold and spiking visual responses of pyramidal neurons in a three-layer cortex

2016 ◽  
Author(s):  
Nathaniel C. Wright ◽  
Ralf Wessel
Keyword(s):  
Membrane Potential ◽  
Cortical Neurons ◽  
Visual Stimulation ◽  
Ex Vivo ◽  
Network Activity ◽  
Visual Responses ◽  
Cortical Function ◽  
Sensory Evoked ◽  
High Conductance

A primary goal of systems neuroscience is to understand cortical function, which typically involves studying spontaneous and sensory-evoked cortical activity. Mounting evidence suggests a strong and complex relationship between the ongoing and evoked state. To date, most work in this area has been based on spiking in populations of neurons. While advantageous in many respects, this approach is limited in scope; it records the activities of a minority of neurons, and gives no direct indication of the underlying subthreshold dynamics. Membrane potential recordings can fill these gaps in our understanding, but are difficult to obtain in vivo. Here, we record subthreshold cortical visual responses in the ex vivo turtle eye-attached whole-brain preparation, which is ideally-suited to such a study. In the absence of visual stimulation, the network is “synchronous”; neurons display network-mediated transitions between low- and high-conductance membrane potential states. The prevalence of these slow-wave transitions varies across turtles and recording sessions. Visual stimulation evokes similar high-conductance states, which are on average larger and less reliable when the ongoing state is more synchronous. Responses are muted when immediately preceded by large, spontaneous high-conductance events. Evoked spiking is sparse, highly variable across trials, and mediated by concerted synaptic inputs that are in general only very weakly correlated with inputs to nearby neurons. Together, these results highlight the multiplexed influence of the cortical network on the spontaneous and sensory-evoked activity of individual cortical neurons.

Layer I neurons of rat neocortex. I. Action potential and repetitive firing properties

1996 ◽  
Vol 76 (2) ◽  
pp. 651-667 ◽  
Author(s):  
F. M. Zhou ◽  
J. J. Hablitz
Keyword(s):  
Membrane Potential ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Repetitive Firing ◽  
Bathing Solution ◽  
Maximal Amplitude ◽  
Frequency Adaptation ◽  
Rat Neocortex ◽  
Layer I ◽  
Firing Properties

1. Whole cell patch-clamp techniques, combined with direct visualization of neurons, were used to study action potential (AP) and repetitive firing properties of layer I neurons in slices of rat neocortex. 2. Layer I neurons had resting membrane potentials (RMP) of -59.8 +/- 4.7 mV (mean +/- SD) and input resistances (RN) of 592 +/- 284 M Omega. Layer II/III pyramidal neurons had RMPs and RNs of -61.5 +/- 5.6 mV and 320 +/- 113 M omega, respectively. A double exponential function was needed to describe the charging curves of both neuron types. In layer I neurons, tau(0) was 45 +/- 22 ms and tau(1) was 5 +/- 3.3 ms whereas in layer II/III pyramidal neurons, tau(0) was 41 +/- 11 ms and tau(1) was 3 +/- 2.6 ms. Estimates of specific membrane resistance (Rm) for layer I and layer II/III cells were 45 +/- 22 and 41 +/- 11 k omega cm2, respectively (Cm was assumed to be 1 microF/cm2). 3. AP threshold was -41 +/- 2 mV in layer I neurons. Spike amplitudes, measured from threshold to peak, were 90.6 +/- 7.7 mV. AP durations, measured both at the base and half maximal amplitude, were 2.5 +/- 0.4 and 1.1 +/- 0.2 ms, respectively. AP 10-90% rise and repolarization times were 0.6 +/- 0.1 and 1.1 +/- 0.2 ms, respectively. In layer II/III pyramidal neurons, AP threshold was -41 +/- 2.5 mV and spike amplitude was 97 +/- 9.7 mV. AP duration at base and half maximal amplitude was 5.4 +/- 1.1 ms and 1.8 +/- 0.2 ms, respectively. AP 10-90% rise and decay times were 0.6 +/- 0.1 ms and 2.8 +/- 0.6 ms, respectively. 4. Layer I neurons were fast spiking cells that showed little frequency adaptation, a large fast afterhyperpolarization (fAHP), and no slow afterhyperpolarization (sAHP). Some cells had a medium afterhyperpolarization (mAHP) and a slow afterdepolarization (sADP). All pyramidal cells in layer II/III and "atypical" pyramidal neurons in upper layer II showed regular spiking behavior, prominent frequency adaptation, and marked sAHPs. 5. In both layer I neurons and layer II/III pyramidal neurons, changes in membrane potential did not greatly alter AP properties. The duration of APs evoked from -50 to -60 mV was only slightly longer, from -80 to -90 mV. The latency to first spike also was not solely dependent on membrane potential. 6. During repetitive firing, APs broadened in both layer I neurons and layer II/III pyramidal neurons. This was most prominent in pyramidal cells. Broadening was dependent on spike frequency and appeared to result from partial inactivation of both outward potassium and inward sodium currents. 7. In layer I neurons, removing Ca2+ from the bathing solution slightly prolonged spike duration and modestly increased AP firing frequency. These results indicate minimal involvement of Ca2+-dependent K+ currents in AP repolarization. fAHPs were reduced whereas sADPs were abolished. In layer II/III pyramidal neurons, removing Ca2+ reduced or blocked mAHPs and sAHPs and decreased or abolished frequency adaptation. 8. Low concentrations (50 microM) of 4-aminopyridine (4-AP) prolonged APs and induced burst-like firing in layer I neurons. In the presence of 4-AP, the spiking behavior of layer I neurons resembled that of regular spiking layer II/III pyramidal cells. At high concentrations (4 mM), 4-AP could induce a delayed depolarization (DD) after each spike in layer I neurons and in a minority of pyramidal neurons. 9. All layer I neurons had a prominent fAHP that was absent or very small in layer II/III pyramidal neurons. fAHP amplitude was inversely related to AP duration. The reduction of fAHPs by 4-AP or during repetitive firing was accompanied by AP prolongation, suggesting that the current underlying fAHP played an essential role in AP repolarization. The fAHP of layer I neurons could be effectively blocked by 4-AP but only slightly reduced by removing Ca2+ from bathing solution, indicating that the fAHP was mediated primarily by a voltage-dependent transient outward current.(ABSTRACT TRUNCATED)

scholarly journals Up and Down States of Cortical Neurons in Focal Limbic Seizures

2019 ◽  
Vol 30 (5) ◽  
pp. 3074-3086 ◽  
Author(s):  
Zongwei Yue ◽  
Isaac G Freedman ◽  
Peter Vincent ◽  
John P Andrews ◽  
Christopher Micek ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Firing Rate ◽  
Cortical Neurons ◽  
Input Resistance ◽  
Loss Of Consciousness ◽  
Cortical Function ◽  
Limbic Seizures ◽  
Electrophysiological Properties ◽  
Up And Down States

Abstract Recent work suggests an important role for cortical–subcortical networks in seizure-related loss of consciousness. Temporal lobe seizures disrupt subcortical arousal systems, which may lead to depressed cortical function and loss of consciousness. Extracellular recordings show ictal neocortical slow waves at about 1 Hz, but it is not known whether these simply represent seizure propagation or alternatively deep sleep-like activity, which should include cortical neuronal Up and Down states. In this study, using in vivo whole-cell recordings in a rat model of focal limbic seizures, we directly examine the electrophysiological properties of cortical neurons during seizures and deep anesthesia. We found that during seizures, the membrane potential of frontal cortical secondary motor cortex layer 5 neurons fluctuates between Up and Down states, with decreased input resistance and increased firing rate in Up states when compared to Down states. Importantly, Up and Down states in seizures are not significantly different from those in deep anesthesia, in terms of membrane potential, oscillation frequency, firing rate, and input resistance. By demonstrating these fundamental similarities in cortical electrophysiology between deep anesthesia and seizures, our results support the idea that a state of decreased cortical arousal may contribute to mechanisms of loss of consciousness during seizures.

scholarly journals Visual experience regulates the intrinsic excitability of visual cortical neurons to maintain sensory function

2018 ◽  
Author(s):  
Alexander P.Y. Brown ◽  
Lee Cossell ◽  
Troy W. Margrie
Keyword(s):  
Cortical Neurons ◽  
Sensory Function ◽  
Intrinsic Excitability ◽  
Dependent Manner ◽  
Cortical Cells ◽  
Network Function ◽  
Sensory Evoked ◽  
Visual Cortical ◽  
Mouse Visual Cortex

This in vivo study shows that both intrinsic and sensory-evoked synaptic properties of layer 2/3 neurons in mouse visual cortex are modified by ongoing visual input. Following visual deprivation, intrinsic properties are significantly altered, although orientation selectivity across the population remains unchanged. We therefore suggest that cortical cells adjust their intrinsic excitability in an activity-dependent manner to compensate for changes in synaptic drive and maintain sensory network function.

Cellular Actions of Urethane on Rat Visual Cortical Neurons In Vitro

2006 ◽  
Vol 95 (6) ◽  
pp. 3865-3874 ◽  
Author(s):  
Michael P. Sceniak ◽  
M. Bruce MacIver
Keyword(s):  
Cortical Neurons ◽  
Signal Transmission ◽  
Membrane Resistance ◽  
Model Systems ◽  
Cortical Function ◽  
Selective Activation ◽  
Postsynaptic Currents ◽  
Visual Cortical

Urethane is widely used in neurophysiological experiments to anesthetize animals, yet little is known about its actions at the cellular and synaptic levels. This limits our ability to model systems-level cortical function using results from urethane-anesthetized preparations. The present study found that action potential discharge of cortical neurons in vitro, in response to depolarizing current, was strongly depressed by urethane and this was accompanied by a significant decrease in membrane resistance. Voltage-clamp experiments suggest that the mechanism of this depression involves selective activation of a Ba2+-sensitive K+ leak conductance. Urethane did not alter excitatory glutamate-mediated or inhibitory (GABAA- or GABAB-mediated) synaptic transmission. Neither the amplitude nor decay time constant of GABAA- or GABAB-mediated monosynaptic inhibitory postsynaptic currents (IPSCs) were altered by urethane, nor was the frequency of spontaneous IPSCs. These results are consistent with observations seen in vivo during urethane anesthesia where urethane produced minimal disruption of signal transmission in the neocortex.

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