Action potentials and relations to the theta rhythm of medial septal neurons in vivo

1999 ◽  
Vol 127 (3) ◽  
pp. 244-258 ◽  
Author(s):  
E. S. Brazhnik ◽  
S. E. Fox
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Celinda M. Kofron ◽  
Tae Yun Kim ◽  
Fabiola Munarin ◽  
Arvin H. Soepriatna ◽  
Rajeev J. Kant ◽  
...  

AbstractCardiotoxicity of pharmaceutical drugs, industrial chemicals, and environmental toxicants can be severe, even life threatening, which necessitates a thorough evaluation of the human response to chemical compounds. Predicting risks for arrhythmia and sudden cardiac death accurately is critical for defining safety profiles. Currently available approaches have limitations including a focus on single select ion channels, the use of non-human species in vitro and in vivo, and limited direct physiological translation. We have advanced the robustness and reproducibility of in vitro platforms for assessing pro-arrhythmic cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts in 3-dimensional microtissues. Using automated algorithms and statistical analyses of eight comprehensive evaluation metrics of cardiac action potentials, we demonstrate that tissue-engineered human cardiac microtissues respond appropriately to physiological stimuli and effectively differentiate between high-risk and low-risk compounds exhibiting blockade of the hERG channel (E4031 and ranolazine, respectively). Further, we show that the environmental endocrine disrupting chemical bisphenol-A (BPA) causes acute and sensitive disruption of human action potentials in the nanomolar range. Thus, this novel human 3D in vitro pro-arrhythmic risk assessment platform addresses critical needs in cardiotoxicity testing for both environmental and pharmaceutical compounds and can be leveraged to establish safe human exposure levels.


2001 ◽  
Vol 18 (4) ◽  
pp. 549-558 ◽  
Author(s):  
A. KURAS ◽  
N. GUTMANIENĖ

Nicotinic acetylcholine receptors are localized on retinotectal axons' terminals in lower vertebrates. The effects of activation of these receptors by endogenous acetylcholine were observed under stimulation of mass optic fibers. This study was designed to determine whether endogenous acetylcholine facilitates frog retinotectal transmission, provided only the synapses of an individual optic axon are activated, and to evaluate the feasible extent of nicotinic facilitation in these synapses by applied agonist. To this end, the effects of cholinergic drugs on the extracellular action and synaptic potentials recorded from the terminal arborization of a separate retinotectal fiber (in layer F of the tectum) were investigated in vivo. Glutamatergic nature of retinotectal synapses was reexamined by treatment with kynurenic acid. Both kynurenic acid (0.25–1 mM) and d-tubocurarine chloride (10–15 μM) significantly depressed the synaptic potentials. Carbamylcholine chloride (50–150 μM) evoked a large augmentation of the synaptic potentials and a slight but statistically significant decrease of the action potentials. D-tubocurarine reduced the effect of carbamylcholine. Pilocarpine hydrochloride (50 μM) had only a weak effect. The paired-pulse facilitation of the synaptic potentials changed significantly under the action of carbamylcholine and d-tubocurarine. The obtained results suggest that the glutamate release from activated synapses of individual retinotectal axons is facilitated by endogenous acetylcholine via presynaptic nicotinic receptors. Under used stimulation conditions, this modulation mechanism was employed only partially since its activation by applied carbamylcholine could enhance synaptic transmission up to 2.8 times.


2001 ◽  
Vol 85 (5) ◽  
pp. 2088-2099 ◽  
Author(s):  
John S. Fitzpatrick ◽  
Garnik Akopian ◽  
John P. Walsh

Two forms of short-term plasticity at inhibitory synapses were investigated in adult rat striatal brain slices using intracellular recordings. Intrastriatal stimulation in the presence of the ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (20 μM) andd,l-2-amino-5-phosphonovaleric acid (50 μM) produced an inhibitory postsynaptic potential (IPSP) that reversed polarity at −76 ± 1 (SE) mV and was sensitive to bicuculline (30 μM). The IPSP rectified at hyperpolarized membrane potentials due in part to activation of K+ channels. The IPSP exhibited two forms of short-term plasticity, paired-pulse depression (PPD) and synaptic augmentation. PPD lasted for several seconds and was greatest at interstimulus intervals (ISIs) of several hundred milliseconds, reducing the IPSP to 80 ± 2% of its control amplitude at an ISI of 200 ms. Augmentation of the IPSP, elicited by a conditioning train of 15 stimuli applied at 20 Hz, was 119 ± 1% of control when sampled 2 s after the conditioning train. Augmentation decayed with a time constant of 10 s. We tested if PPD and augmentation modify the ability of the IPSP to prevent the generation of action potentials. A train of action potentials triggered by a depolarizing current injection of constant amplitude could be interrupted by stimulation of an IPSP. If this IPSP was the second in a pair of IPSPs, it was less effective in blocking spikes due to PPD. By contrast, augmented IPSPs were more effective in blocking spikes. The same results were achieved when action potentials were triggered by a depolarizing current injection of varying amplitude, a manipulation that produces nearly identical spike times from trial to trial and approximates the in vivo behavior of these neurons. These results demonstrate that short-term plasticity of inhibition can modify the output of the striatum and thus may be an important component of information processing during behaviors that involve the striatum.


eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Angus Chadwick ◽  
Mark CW van Rossum ◽  
Matthew F Nolan

Hippocampal place cells encode an animal's past, current, and future location through sequences of action potentials generated within each cycle of the network theta rhythm. These sequential representations have been suggested to result from temporally coordinated synaptic interactions within and between cell assemblies. Instead, we find through simulations and analysis of experimental data that rate and phase coding in independent neurons is sufficient to explain the organization of CA1 population activity during theta states. We show that CA1 population activity can be described as an evolving traveling wave that exhibits phase coding, rate coding, spike sequences and that generates an emergent population theta rhythm. We identify measures of global remapping and intracellular theta dynamics as critical for distinguishing mechanisms for pacemaking and coordination of sequential population activity. Our analysis suggests that, unlike synaptically coupled assemblies, independent neurons flexibly generate sequential population activity within the duration of a single theta cycle.


Author(s):  
H. R. Olpe ◽  
H. Jutzeler ◽  
E. Kueng ◽  
P. Campiche ◽  
K. Klebs ◽  
...  

1988 ◽  
Vol 59 (5) ◽  
pp. 1476-1496 ◽  
Author(s):  
R. S. Jones ◽  
U. Heinemann

1. Extracellular recordings were made from slices of hippocampus plus parahippocampal regions maintained in vitro. Field potentials, recorded in the entorhinal cortex after stimulation in the subiculum, resembled those observed in vivo. 2. Washout of magnesium from the slices resulted in paroxysmal events which resembled those occurring during sustained seizures in vivo. These events were greatest in amplitude and duration in layers IV/V of the medial entorhinal cortex and could occur both spontaneously and in response to subicular stimulation. Spontaneous seizure-like events were not prevented by severing the connections between the hippocampus and entorhinal cortex, but much smaller and shorter events occurring in the dentate gyrus were stopped by this manipulation. Both spontaneous and evoked paroxysmal events were blocked by perfusion with the N-methyl-D-aspartate (NMDA) receptor antagonist, DL-2-amino-5-phosphonovalerate (2-AP5). 3. Neurons in layers IV/V were characterized by intracellular recording. Injection of depolarizing current in most cells evoked a train of nondecrementing action potentials with only weak spike frequency accommodation and little or no posttrain after hyperpolarization. 4. A small number of cells displayed burst response when depolarized by positive current. The burst consisted of a slow depolarization with superimposed action potentials which decreased in amplitude and increased in duration during the discharge. The burst was terminated by a strong after hyperpolarization and thereafter, during prolonged current pulses a train of nondecrementing spikes occurred. The burst response remained if the cell was held at hyperpolarized levels but was inactivated by holding the cell at a depolarized level. 5. Depolarizing synaptic potentials could be evoked by stimulation in the subiculum. A delayed and prolonged depolarization clearly decremented with membrane hyperpolarization and, occasionally, increased with depolarization. 6. Washout of magnesium from the slices resulted in an enhancement of the late depolarization and a reversal of its voltage dependence. Eventually a single shock to the subiculum evoked a large all-or-none paroxysmal depolarization associated with a massive increase in membrane conductance. Similar events occurred spontaneously in all cells tested. The paroxysmal depolarizations, both spontaneous and evoked, were rapidly blocked by 2-AP5. 7. It is concluded that medial entorhinal cortical cells possess several intrinsic and synaptic properties which confer an extreme susceptibility to generation of sustained seizure activity.(ABSTRACT TRUNCATED AT 400 WORDS)


1997 ◽  
Vol 77 (4) ◽  
pp. 1697-1715 ◽  
Author(s):  
Edward A. Stern ◽  
Anthony E. Kincaid ◽  
Charles J. Wilson

Stern, Edward A., Anthony E. Kincaid, and Charles J. Wilson. Spontaneous subthreshold membrane potential fluctuations and action potential variability of rat corticostriatal and striatal neurons in vivo. J. Neurophysiol. 77: 1697–1715, 1997. We measured the timing of spontaneous membrane potential fluctuations and action potentials of medial and lateral agranular corticostriatal and striatal neurons with the use of in vivo intracellular recordings in urethan-anesthetized rats. All neurons showed spontaneous subthreshold membrane potential shifts from 7 to 32 mV in amplitude, fluctuating between a hyperpolarized down state and depolarized up state. Action potentials arose only during the up state. The membrane potential state transitions showed a weak periodicity with a peak frequency near 1 Hz. The peak of the frequency spectra was broad in all neurons, indicating that the membrane potential fluctuations were not dominated by a single periodic function. At frequencies >1 Hz, the log of magnitude decreased linearly with the log of frequency in all neurons. No serial dependence was found for up and down state durations, or for the time between successive up or down state transitions, showing that the up and down state transitions are not due to superimposition of noisy inputs onto a single frequency. Monte Carlo simulations of stochastic synaptic inputs to a uniform finite cylinder showed that the Fourier spectra obtained for corticostriatal and striatal neurons are inconsistent with a Poisson-like synaptic input, demonstrating that the up state is not due to an increase in the strength of an unpatterned synaptic input. Frequency components arising from state transitions were separated from those arising from the smaller membrane potential fluctuations within each state. A larger proportion of the total signal was represented by the fluctuations within states, especially in the up state, than was predicted by the simulations. The individual state spectra did not correspond to those of random synaptic inputs, but reproduced the spectra of the up and down state transitions. This suggests that the process causing the state transitions and the process responsible for synaptic input may be the same. A high-frequency periodic component in the up states was found in the majority of the corticostriatal cells in the sample. The average size of the component was not different between neurons injected with QX-314 and control neurons. The high-frequency component was not seen in any of our sample of striatal cells. Corticostriatal and striatal neurons' coefficients of variation of interspike intervals ranged from 1.0 to 1.9. When interspike intervals including a down state were subtracted from the calculation, the coefficient of variation ranged from 0.4 to 1.1, indicating that a substantial proportion of spike interval variance was due to the subthreshold membrane potential fluctuations.


1981 ◽  
Vol 241 (5) ◽  
pp. H700-H707 ◽  
Author(s):  
D. W. Snyder ◽  
W. A. Crafford ◽  
J. L. Glashow ◽  
D. Rankin ◽  
B. E. Sobel ◽  
...  

Lysophosphoglycerides accumulate in ischemic myocardium. To determine whether lysophosphatidylcholine (LPC) concentrations increase in extracellular fluid and may be arrhythmogenic, the anterior descending coronary artery of the open-chest cat (n = 12) was perfused with a Krebs-albumin solution after 10 min of ischemia and the effluent assayed for LPC. A twofold increase in LPC (0.097 +/- 0.02 to 0.170 +/- 0.03 mM) was observed. Microelectrode intracellular recordings from from normal feline endocardium at pH 7.4 in vitro revealed little change in action potentials when superfused with feline plasma despite augmented LPC to twice normal levels (0.74 mM). However, at pH 6.7, marked changes were elicited by LPC-enriched plasma including diminished resting membrane potential (-96 +/- 1 to -35 +/- 7 mV), amplitude (102 +/- 3 to 36 +/- 8 mV), maximum rate of rise (Vmax) of phase 0 (178 +/- 24 to 26 +/- 11 V/s), and conduction velocity with fractionation of the action potential. Acidified control plasma decreased only Vmax (from 161 to 57 V/s). Thus LPC increases twofold in effluents from cat myocardium in vivo after 10 min of ischemia and, coupled with ischemia-induced acidosis, is sufficient to induce marked electrophysiological derangements in vitro.


2019 ◽  
Vol 12 (01) ◽  
pp. 1850040
Author(s):  
Muqun Yang ◽  
Tian Guan ◽  
Yonghong He

Infrared neuron stimulation is regarded as an innovative approach for stimulating cochleae in animals while the exact mechanism still remains unknown. In this paper, we studied compound action potentials of guinea pig cochleae with chronic or acute deafness. We recorded optical compound action potentials and analyzed stretched cochlear preparations by fluorescence microscopy. Photoacoustic signals were measured by hydrophone and microphone, respectively. In our experiment, we observed a switch response effect in vitro and in vivo experiments. Therefore, we proposed photoacoustic effect could invoke auditory response in infrared neuron stimulation.


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