scholarly journals Surface charge impact in low-magnesium model of seizure in rat hippocampus

2012 ◽  
Vol 107 (1) ◽  
pp. 417-423 ◽  
Author(s):  
Dmytro Isaev ◽  
Gleb Ivanchick ◽  
Volodymyr Khmyz ◽  
Elena Isaeva ◽  
Alina Savrasova ◽  
...  
Keyword(s):  
Surface Charge ◽  
Pyramidal Neurons ◽  
Seizure Threshold ◽  
Neuronal Membrane ◽  
Voltage Sensitivity ◽  
Hippocampal Pyramidal Neurons ◽  
Low Magnesium ◽  
Initial Stage ◽  
Pyramidal Layer ◽  
Hippocampal Ca1

Putative mechanisms of induction and maintenance of seizure-like activity (SLA) in the low Mg2+ model of seizures are: facilitation of NMDA receptors and decreased surface charge screening near voltage-gated channels. We have estimated the role of such screening in the early stages of SLA development at both physiological and room temperatures. External Ca2+ and Mg2+ promote a depolarization shift of the sodium channel voltage sensitivity; when examined in hippocampal pyramidal neurons, the effect of Ca2+ was 1.4 times stronger than of Mg2+. Removing Mg2+ from the extracellular solution containing 2 mM Ca2+ induced recurrent SLA in hippocampal CA1 pyramidal layer in 67% of slices. Reduction of [Ca2+]o to 1 mM resulted in 100% appearance of recurrent SLA or continuous SLA. Both delay before seizure activity and the inter-SLA time were significantly reduced. Characteristics of seizures evoked in low Mg2+/1 mM Ca2+/3.5 K+ were similar to those obtained in low Mg2+/2 Ca2+/5mM K+, suggesting that reduction of [Ca2+]o to 1 mM is identical to the increase in [K+]o to 5 mM in terms of changes in cellular excitability and seizure threshold. An increase of [Ca2+]o to 3 mM completely abolished SLA generation even in the presence of 5 mM [K+]o. A large variation in the ability of [Ca2+]o to stop epileptic discharges in initial stage of SLA was found. Our results indicate that surface charge of the neuronal membrane plays a crucial role in the initiation of low Mg2+-induced seizures. Furthermore, our study suggests that Ca2+ and Mg2+, through screening of surface charge, have important anti-seizure and antiepileptic properties.

Cumulative Effects of Glutamate Microstimulation on Ca2+ Responses of CA1 Hippocampal Pyramidal Neurons in Slice

2000 ◽  
Vol 83 (1) ◽  
pp. 90-98 ◽  
Author(s):  
John A. Connor ◽  
Robert J. Cormier
Keyword(s):  
Time Course ◽  
Pyramidal Neurons ◽  
Stratum Radiatum ◽  
Neuron Death ◽  
Hippocampal Pyramidal Neurons ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
High Resolution Images ◽  
Stimulation Of

Glutamate stimulation of hippocampal CA1 neurons in slice was delivered via iontophoresis from a microelectrode. Five pulses (∼5 μA, 10 s duration, repeated at 1 min intervals) were applied with the electrode tip positioned in the stratum radiatum near the dendrites of a neuron filled with the Ca2+ indicator fura-2. A single stimulus set produced Ca2+ elevations that ranged from several hundred nM to several μM and that, in all but a few neurons, recovered within 1 min of stimulus termination. Subsequent identical stimulation produced Ca2+ elevations that outlasted the local glutamate elevations by several minutes as judged by response recoveries in neighboring cells or in other parts of the same neuron. These long responses ultimately recovered but persisted for up to 10 min and were most prominent in the mid and distal dendrites. Recovery was not observed for responses that spread to the soma. The elevated Ca2+ levels were accompanied by membrane depolarization but did not appear to depend on the depolarization. High-resolution images demonstrated responsive areas that involved only a few μm of dendrite. Our results confirm the previous general findings from isolated and cell culture neurons that glutamate stimulation, if carried beyond a certain range, results in long-lasting Ca2+ elevation. The response characterized here in mature in situ neurons was significantly different in terms of time course and reversibility. We suggest that the extended Ca2+ elevations might serve not only as a trigger for delayed neuron death but, where more spatially restricted, as a signal for local remodeling in dendrites.

scholarly journals Slowly inactivating component of Na+ current in peri-somatic region of hippocampal CA1 pyramidal neurons

2013 ◽  
Vol 109 (5) ◽  
pp. 1378-1390 ◽  
Author(s):  
Yul Young Park ◽  
Daniel Johnston ◽  
Richard Gray
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Peak Amplitude ◽  
Neuronal Membrane ◽  
Inactivation Kinetics ◽  
Channel Blockers ◽  
Hippocampal Ca1 ◽  
Ramp Voltage ◽  
Dendritic Spikes ◽  
Voltage Gated Ion Channels

The properties of voltage-gated ion channels on the neuronal membrane shape electrical activity such as generation and backpropagation of action potentials, initiation of dendritic spikes, and integration of synaptic inputs. Subthreshold currents mediated by sodium channels are of interest because of their activation near rest, slow inactivation kinetics, and consequent effects on excitability. Modulation of these currents can also perturb physiological responses of a neuron that might underlie pathological states such as epilepsy. Using nucleated patches from the peri-somatic region of hippocampal CA1 neurons, we recorded a slowly inactivating component of the macroscopic Na+ current (which we have called INaS) that shared many biophysical properties with the persistent Na+ current, INaP, but showed distinctively faster inactivating kinetics. Ramp voltage commands with a velocity of 400 mV/s were found to elicit this component of Na+ current reliably. INaS also showed a more hyperpolarized I-V relationship and slower inactivation than those of the fast transient Na+ current ( INaT) recorded in the same patches. The peak amplitude of INaS was proportional to the peak amplitude of INaT but was much smaller in amplitude. Hexanol, riluzole, and ranolazine, known Na+ channel blockers, were tested to compare their effects on both INaS and INaT. The peak conductance of INaS was preferentially blocked by hexanol and riluzole, but the shift of half-inactivation voltage ( V1/2) was only observed in the presence of riluzole. Current-clamp measurements with hexanol suggested that INaS was involved in generation of an action potential and in upregulation of neuronal excitability.

scholarly journals Metformin Enhances Excitatory Synaptic Transmission onto Hippocampal CA1 Pyramidal Neurons

2020 ◽  
Vol 10 (10) ◽  
pp. 706
Author(s):  
Wen-Bing Chen ◽  
Jiang Chen ◽  
Zi-Yang Liu ◽  
Bin Luo ◽  
Tian Zhou ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Hippocampal Pyramidal Neurons ◽  
Beneficial Effects ◽  
Ca1 Pyramidal Neurons ◽  
Postsynaptic Currents ◽  
Hippocampal Ca1

Metformin (Met) is a first-line drug for type 2 diabetes mellitus (T2DM). Numerous studies have shown that Met exerts beneficial effects on a variety of neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). However, it is still largely unclear how Met acts on neurons. Here, by treating acute hippocampal slices with Met (1 μM and 10 μM) and recording synaptic transmission as well as neuronal excitability of CA1 pyramidal neurons, we found that Met treatments significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs), but not amplitude. Neither frequency nor amplitude of miniature inhibitory postsynaptic currents (mIPSCs) were changed with Met treatments. Analysis of paired-pulse ratios (PPR) demonstrates that enhanced presynaptic glutamate release from terminals innervating CA1 hippocampal pyramidal neurons, while excitability of CA1 pyramidal neurons was not altered. Our results suggest that Met preferentially increases glutamatergic rather than GABAergic transmission in hippocampal CA1, providing a new insight on how Met acts on neurons.

scholarly journals Kv4 Accessory Protein DPPX (DPP6) is a Critical Regulator of Membrane Excitability in Hippocampal CA1 Pyramidal Neurons

2008 ◽  
Vol 100 (4) ◽  
pp. 1835-1847 ◽  
Author(s):  
Jinhyun Kim ◽  
Marcela S. Nadal ◽  
Ann M. Clemens ◽  
Matthew Baron ◽  
Sung-Cherl Jung ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Input Resistance ◽  
Physiological Effect ◽  
Membrane Excitability ◽  
Hippocampal Pyramidal Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 ◽  
Kv4 Channels ◽  
Steady State Inactivation ◽  
Heterologous Expression Systems

A-type K+ currents have unique kinetic and voltage-dependent properties that allow them to finely tune synaptic integration, action potential (AP) shape and firing patterns. In hippocampal CA1 pyramidal neurons, Kv4 channels make up the majority of the somatodendritic A-type current. Studies in heterologous expression systems have shown that Kv4 channels interact with transmembrane dipeptidyl-peptidase-like proteins (DPPLs) to regulate the surface trafficking and biophysical properties of Kv4 channels. To investigate the influence of DPPLs in a native system, we conducted voltage-clamp experiments in patches from CA1 pyramidal neurons expressing short-interfering RNA (siRNA) targeting the DPPL variant known to be expressed in hippocampal pyramidal neurons, DPPX (siDPPX). In accordance with heterologous studies, we found that DPPX downregulation in neurons resulted in depolarizing shifts of the steady-state inactivation and activation curves, a shallower conductance-voltage slope, slowed inactivation, and a delayed recovery from inactivation for A-type currents. We carried out current-clamp experiments to determine the physiological effect of the A-type current modifications by DPPX. Neurons expressing siDPPX exhibited a surprisingly large reduction in subthreshold excitability as measured by a decrease in input resistance, delayed time to AP onset, and an increased AP threshold. Suprathreshold DPPX downregulation resulted in slower AP rise and weaker repolarization. Computer simulations supported our experimental results and demonstrated how DPPX remodeling of A-channel properties can result in opposing sub- and suprathreshold effects on excitability. The Kv4 auxiliary subunit DPPX thus acts to increase neuronal responsiveness and enhance signal precision by advancing AP initiation and accelerating both the rise and repolarization of APs.

Ca2+ Channel Antagonist U-92032 Inhibits Both T-Type Ca2+ Channels and Na+ Channels in Hippocampal CA1 Pyramidal Neurons

1997 ◽  
Vol 77 (2) ◽  
pp. 1023-1028 ◽  
Author(s):  
Robert B. Avery ◽  
Daniel Johnston
Keyword(s):  
Pyramidal Neurons ◽  
Channel Blocker ◽  
Cell Voltage ◽  
Ionic Currents ◽  
Hippocampal Pyramidal Neurons ◽  
Voltage Gated ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 ◽  
Old Rats ◽  
Ca2 Channels

Avery, Robert B. and Daniel Johnston. Ca2+ channel antagonist U-92032 inhibits both T-type Ca2+ channels and Na+ channels in hippocampal CA1 pyramidal neurons. J. Neurophysiol. 77: 1023–1028, 1997. The effects of 7-[[4-[bis(4-fluoropheny l ) - m e t h y l ] - 1 - p i p e r a z i n y l ] m e t h y l ] - 2 - [ ( 2 - h y d r o x y e t h y l ) a m i n o ]4 -( 1 - m e t h y l e t h y l ) - 2 , 4 , 6 - c y c l o h e p t a t r i e n - 1 - o n e  ( U - 9 2 0 3 2 ) ,  anewly described Ca2+ channel blocker, on voltage-gated ionic currents were measured. Whole cell voltage-clamp records were obtained from acutely isolated CA1 hippocampal pyramidal neurons from 7- to 14-day-old rats. Dimethyl sulfoxide, at either 0.01% or 0.1%, partially inhibited T-type Ca2+ currents (∼20% inhibition) but not high-voltage-activated (HVA) Ca2+ currents. Ethanol (0.2%) did not affect Ca2+ currents. U-92032 selectively inhibited T-type Ca2+ currents (median inhibiting concentration ∼ 500 nM). HVA Ca2+ currents were less sensitive, with ∼75% of the current resistant at 10 μM. Inhibition of Ca2+ currents was reversible. U-92032 inhibited Na+ currents at concentrations similar to those required for T-type currents (>33% block at 1 μM). Block of Na+ currents took several minutes to develop and was irreversible. Voltage-gated K+ currents were insensitive to U-92032 (1 or 10 μM). These results indicate that U-92032 inhibits both T-type Ca2+ channels and Na+ channels, constraining its utility in certain studies. Among Ca2+ channels, however, U-92032 should prove a useful tool for distinguishing physiological contributions of T-type channels.

Watermaze Learning Enhances Excitability of CA1 Pyramidal Neurons

2003 ◽  
Vol 90 (4) ◽  
pp. 2171-2179 ◽  
Author(s):  
M. Matthew Oh ◽  
Amy G. Kuo ◽  
Wendy W. Wu ◽  
Evgeny A. Sametsky ◽  
John F. Disterhoft
Keyword(s):  
Pyramidal Neurons ◽  
Dorsal Hippocampus ◽  
Eyeblink Conditioning ◽  
Hippocampal Pyramidal Neurons ◽  
Ca1 Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Platform Location ◽  
Dorsal Hippocampal ◽  
Hippocampal Ca1 ◽  
Trace Eyeblink Conditioning

The dorsal hippocampus is crucial for learning the hidden-platform location in the hippocampus-dependent, spatial watermaze task. We have previously demonstrated that the postburst afterhyperpolarization (AHP) of hippocampal pyramidal neurons is reduced after acquisition of the hippocampus-dependent, temporal trace eyeblink conditioning task. We report here that the AHP and one or more of its associated currents ( IAHP and/or s IAHP) are reduced in dorsal hippocampal CA1 pyramidal neurons from rats that learned the watermaze task as compared with neurons from control rats. This reduction was a learning-induced phenomenon as the AHP of CA1 neurons from rats that failed to learn the hidden-platform location was similar to that of neurons from control rats. We propose that reduction of the AHP in pyramidal neurons in regions crucial for learning is a cellular mechanism of learning that is conserved across species and tasks.

Subthreshold synaptic activation of voltage-gated Ca2+ channels mediates a localized Ca2+ influx into the dendrites of hippocampal pyramidal neurons

1995 ◽  
Vol 74 (3) ◽  
pp. 1335-1342 ◽  
Author(s):  
J. C. Magee ◽  
G. Christofi ◽  
H. Miyakawa ◽  
B. Christie ◽  
N. Lasser-Ross ◽  
...  
Keyword(s):  
High Speed ◽  
Pyramidal Neurons ◽  
Low Voltage ◽  
Synaptic Activity ◽  
Hippocampal Pyramidal Neurons ◽  
Low Concentrations ◽  
Hippocampal Ca1 ◽  
Apical Dendrites ◽  
Whole Cell Recordings ◽  
Ca2 Channels

1. Whole cell recordings and high-speed fluorescence imaging were used to investigate the spatial and temporal characteristics of Ca2+ influx during synaptic activity in hippocampal CA1 pyramidal neurons. Brief, subthreshold trains of synaptic potentials elicited by Schaffer collateral stimulation produced transient increases in [Ca2+]i in the apical dendrites near the site of synaptic input. The rises in [Ca2+]i were not due to Ca2+ entry through N-methyl-D-aspartate (NMDA)-activated or non-NMDA-activated glutamate channels, but were reduced by low concentrations of Ni2+. Hyperpolarizing prepulses caused an increase in the synaptically evoked Ca2+ transients, whereas strong hyperpolarization during the train prevented the rise in [Ca2+]i. The data suggest that subthreshold synaptic activity can open low-voltage-activated (T-type) Ca2+ channels and produce a local increase in intradendritic [Ca2+]. Such local increases in [Ca2+]i may be important for modulating the strength of synaptic connections.

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