scholarly journals Diazepam and ethanol differently modulate neuronal activity in organotypic cortical cultures

2019 ◽  
Author(s):  
Matthias Kreuzer ◽  
Paul S García ◽  
Verena Brucklacher-Waldert ◽  
Rebecca Claasen ◽  
Gerhard Schneider ◽  
...  
Keyword(s):  
Action Potential ◽  
Gabaa Receptors ◽  
Cortical Neurons ◽  
Spectral Power ◽  
Spectral Composition ◽  
Field Potential ◽  
Cortical Network ◽  
Ethanol Administration ◽  
Action Potential Firing ◽  
Experimental Conditions

Abstract Background: The pharmacodynamic results of diazepam and ethanol administration are similar, in that each can mediate amnestic, sedative-hypnotic effects. Although each of these molecules effectively reduce the activity of central neurons, diazepam does so through modulation of a more specific set of receptor targets (GABAA receptors containing a g-subunit), while alcohol is less selective in its receptor bioactivity. Our investigation focuses on divergent actions of diazepam and ethanol on the firing patterns of cultured cortical neurons. Method: We used electrophysiological recordings from organotypic slice cultures derived from Sprague-Dawley rat neocortex. We exposed these cultures to either diazepam (15 and 30 µM, n = 7) or ethanol (30 and 60 mM, n = 11) and recorded the electrical activity at baseline and experimental conditions. For analysis, we extracted the episodes of spontaneous activity, i.e., cortical up-states. After separation of action potential and local field potential (LFP) activity, we looked at differences in the number of action potentials, in the spectral power of the LFP, as well as in the coupling between action potential and LFP phase. Results: While both substances seem to decrease neocortical action potential firing in a not significantly different (p=0.659, Mann-Whitney U) fashion, diazepam increases the spectral power of the up-state without significantly impacting the spectral composition, whereas ethanol does not significantly change the spectral power but the oscillatory architecture of the up-state as revealed by the Friedman test with Bonferroni correction (p<0.05). Further, the action potential to LFP-phase coupling reveals a synchronizing effect of diazepam for a wide frequency range and a narrow-band de-synchronizing effect for ethanol (p<0.05, Kolmogorov-Smirnov test). Conclusion: Diazepam and ethanol, induce specific patterns of network depressant actions. Diazepam induces cortical network inhibition and increased synchronicity via gamma subunit containing GABAA receptors. Ethanol also induces cortical network inhibition, but without an increase in synchronicity via a wider span of molecular targets.

scholarly journals Diazepam and ethanol differently modulate neuronal activity in organotypic cortical cultures

2019 ◽  
Author(s):  
Matthias Kreuzer ◽  
Paul S García ◽  
Verena Brucklacher-Waldert ◽  
Rebecca Claasen ◽  
Gerhard Schneider ◽  
...  
Keyword(s):  
Action Potential ◽  
Gabaa Receptors ◽  
Cortical Neurons ◽  
Spectral Power ◽  
Spectral Composition ◽  
Field Potential ◽  
Cortical Network ◽  
Ethanol Administration ◽  
Action Potential Firing ◽  
Experimental Conditions

Abstract Background: The pharmacodynamic results of diazepam and ethanol administration are similar, in that each can mediate amnestic, sedative-hypnotic effects. Although each of these molecules effectively reduce the activity of central neurons, diazepam does so through modulation of a more specific set of receptor targets (GABAA receptors containing a g-subunit), while alcohol is less selective in its receptor bioactivity. Our investigation focuses on divergent actions of diazepam and ethanol on the firing patterns of cultured cortical neurons. Method: We used electrophysiological recordings from organotypic slice cultures derived from Sprague-Dawley rat neocortex. We exposed these cultures to either diazepam (15 and 30 µM, n = 7) or ethanol (30 and 60 mM, n = 11) and recorded the electrical activity at baseline and experimental conditions. For analysis, we extracted the episodes of spontaneous activity, i.e., cortical up-states. After separation of action potential and local field potential (LFP) activity, we looked at differences in the number of action potentials, in the spectral power of the LFP, as well as in the coupling between action potential and LFP phase. Results: While both substances seem to decrease neocortical action potential firing in a not significantly different (p=0.659, Mann-Whitney U) fashion, diazepam increases the spectral power of the up-state without significantly impacting the spectral composition, whereas ethanol does not significantly change the spectral power but the oscillatory architecture of the up-state as revealed by the Friedman test with Bonferroni correction (p<0.05). Further, the action potential to LFP-phase coupling reveals a synchronizing effect of diazepam for a wide frequency range and a narrow-band de-synchronizing effect for ethanol (p<0.05, Kolmogorov-Smirnov test). Conclusion: Diazepam and ethanol, induce specific patterns of network depressant actions. Diazepam induces cortical network inhibition and increased synchronicity via gamma subunit containing GABAA receptors. Ethanol also induces cortical network inhibition, but without an increase in synchronicity via a wider span of molecular targets.

scholarly journals Diazepam and ethanol differently modulate neuronal activity in organotypic cortical cultures

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Matthias Kreuzer ◽  
Paul S. García ◽  
Verena Brucklacher-Waldert ◽  
Rebecca Claassen ◽  
Gerhard Schneider ◽  
...  
Keyword(s):  
Action Potential ◽  
Cortical Neurons ◽  
Spectral Power ◽  
Spectral Composition ◽  
Field Potential ◽  
Cortical Network ◽  
Ethanol Administration ◽  
Sprague Dawley ◽  
Action Potential Firing ◽  
Experimental Conditions

Abstract Background The pharmacodynamic results of diazepam and ethanol administration are similar, in that each can mediate amnestic and sedative-hypnotic effects. Although each of these molecules effectively reduce the activity of central neurons, diazepam does so through modulation of a more specific set of receptor targets (GABAA receptors containing a γ-subunit), while alcohol is less selective in its receptor bioactivity. Our investigation focuses on divergent actions of diazepam and ethanol on the firing patterns of cultured cortical neurons. Method We used electrophysiological recordings from organotypic slice cultures derived from Sprague–Dawley rat neocortex. We exposed these cultures to either diazepam (15 and 30 µM, n = 7) or ethanol (30 and 60 mM, n = 11) and recorded the electrical activity at baseline and experimental conditions. For analysis, we extracted the episodes of spontaneous activity, i.e., cortical up-states. After separation of action potential and local field potential (LFP) activity, we looked at differences in the number of action potentials, in the spectral power of the LFP, as well as in the coupling between action potential and LFP phase. Results While both substances seem to decrease neocortical action potential firing in a not significantly different (p = 0.659, Mann–Whitney U) fashion, diazepam increases the spectral power of the up-state without significantly impacting the spectral composition, whereas ethanol does not significantly change the spectral power but the oscillatory architecture of the up-state as revealed by the Friedman test with Bonferroni correction (p < 0.05). Further, the action potential to LFP-phase coupling reveals a synchronizing effect of diazepam for a wide frequency range and a narrow-band de-synchronizing effect for ethanol (p < 0.05, Kolmogorov–Smirnov test). Conclusion Diazepam and ethanol, induce specific patterns of network depressant actions. Diazepam induces cortical network inhibition and increased synchronicity via gamma subunit containing GABAA receptors. Ethanol also induces cortical network inhibition, but without an increase in synchronicity via a wider span of molecular targets.

scholarly journals Diazepam and ethanol differently modulate neuronal activity in organotypic cortical cultures

2019 ◽  
Author(s):  
Matthias Kreuzer ◽  
Paul S García ◽  
Verena Brucklacher-Waldert ◽  
Rebecca Claasen ◽  
Gerhard Schneider ◽  
...  
Keyword(s):  
Action Potential ◽  
Cortical Neurons ◽  
Spectral Power ◽  
Spectral Composition ◽  
Field Potential ◽  
Cortical Network ◽  
Ethanol Administration ◽  
Sprague Dawley ◽  
Action Potential Firing ◽  
Experimental Conditions

Abstract Background: The pharmacodynamic results of diazepam and ethanol administration are similar, in that each can mediate amnestic, sedative-hypnotic effects. Although each of these molecules effectively reduces the activity of central neurons, diazepam does so through modulation of a more specific set of receptor targets (GABAA receptors containing a γ-subunit), while alcohol is less selective in its receptor bioactivity. Our investigation focuses on divergent actions of diazepam and ethanol on the firing patterns of cultured cortical neurons. Method: We used electrophysiological recordings from organotypic slice cultures derived from Sprague-Dawley rat neocortex. We exposed these cultures to either diazepam (15 and 30 µM) or ethanol (30 and 60 mM) and recorded the electrical activity at baseline and experimental conditions. For analysis, we extracted the episodes of spontaneous activity, i.e., cortical up-states. After separation of action potential and local field potential (LFP) activity, we looked at differences in the number of action potentials, in the spectral power of the LFP, as well as in the coupling between action potential and LFP phase. Results: While both substances seem to decrease neocortical action potential firing in a similar fashion, diazepam seems to increase the spectral power of the up-state without impacting the spectral composition, whereas ethanol does not change the spectral power but the oscillatory architecture of the up-state. Further, the action potential to LFP-phase coupling reveals a synchronizing effect of diazepam and a (rather weak) de-synchronizing effect for ethanol. Conclusion: Diazepam and ethanol, induce specific patterns of network depressant actions. Diazepam, via gamma subunit containing GABAA receptors, induces cortical network inhibition and increased synchronicity. Ethanol, via a wider span of molecular targets, also induces cortical network inhibition, but without an increase in synchronicity.

Spike-Wave Complexes and Fast Components of Cortically Generated Seizures. IV. Paroxysmal Fast Runs in Cortical and Thalamic Neurons

1998 ◽  
Vol 80 (3) ◽  
pp. 1495-1513 ◽  
Author(s):  
Igor Timofeev ◽  
François Grenier ◽  
Mircea Steriade
Keyword(s):  
Electrical Stimulation ◽  
High Frequency ◽  
Cortical Neurons ◽  
Field Potential ◽  
Thalamic Nuclei ◽  
Experimental Conditions ◽  
Thalamic Neurons ◽  
Single Action ◽  
Spike Bursts ◽  
Spike Wave

Timofeev, Igor, François Grenier, and Mircea Steriade. Spike-wave complexes and fast components of cortically generated seizures. IV. Paroxysmal fast runs in cortical and thalamic neurons. J. Neurophysiol. 80: 1495–1513, 1998. In the preceding papers of this series, we have analyzed the cellular patterns and synchronization of neocortical seizures occurring spontaneously or induced by electrical stimulation or cortical infusion of bicuculline under a variety of experimental conditions, including natural states of vigilance in behaving animals and acute preparations under different anesthetics. The seizures consisted of two distinct components: spike-wave (SW) or polyspike-wave (PSW) at 2–3 Hz and fast runs at 10–15 Hz. Because the thalamus is an input source and target of cortical neurons, we investigated here the seizure behavior of thalamic reticular (RE) and thalamocortical (TC) neurons, two major cellular classes that have often been implicated in the generation of paroxysmal episodes. We performed single and dual simultaneous intracellular recordings, in conjunction with multisite field potential and extracellular unit recordings, from neocortical areas and RE and/or dorsal thalamic nuclei under ketamine-xylazine and barbiturate anesthesia. Both components of seizures were analyzed, but emphasis was placed on the fast runs because of their recent investigation at the cellular level. 1) The fast runs occurred at slightly different frequencies and, therefore, were asynchronous in various cortical neuronal pools. Consequently, dorsal thalamic nuclei, although receiving convergent inputs from different neocortical areas involved in seizure, did not express strongly synchronized fast runs. 2) Both RE and TC cells were hyperpolarized during seizure episodes with SW/PSW complexes and relatively depolarized during the fast runs. As known, hyperpolarization of thalamic neurons deinactivates a low-threshold conductance that generates high-frequency spike bursts. Accordingly, RE neurons discharged prolonged high-frequency spike bursts in close time relation with the spiky component of cortical SW/PSW complexes, whereas they fired single action potentials, spike doublets, or triplets during the fast runs. In TC cells, the cortical fast runs were reflected as excitatory postsynaptic potentials appearing after short latencies that were compatible with monosynaptic activation through corticothalamic pathways. 3) The above data suggested the cortical origin of these seizures. To further test this hypothesis, we performed experiments on completely isolated cortical slabs from suprasylvian areas 5 or 7 and demonstrated that electrical stimulation within the slab induces seizures with fast runs and SW/PSW complexes, virtually identical to those elicited in intact-brain animals. The conclusion of all papers in this series is that complex seizure patterns, resembling those described at the electroencephalogram level in different forms of clinical seizures with SW/PSW complexes and, particularly, in the Lennox-Gastaut syndrome of humans, are generated in neocortex. Thalamic neurons reflect cortical events as a function of membrane potential in RE/TC cells and degree of synchronization in cortical neuronal networks.

Development of hypersynchrony in the cortical network during chemoconvulsant-induced epileptic seizures in vivo

2012 ◽  
Vol 107 (6) ◽  
pp. 1718-1730 ◽  
Author(s):  
Adi Cymerblit-Sabba ◽  
Yitzhak Schiller
Keyword(s):  
Action Potential ◽  
Early Phase ◽  
Epileptic Seizures ◽  
Firing Frequency ◽  
Cortical Network ◽  
Small Subset ◽  
Action Potential Firing ◽  
Neuronal Synchronization ◽  
Potential Firing

The prevailing view of epileptic seizures is that they are caused by increased hypersynchronous activity in the cortical network. However, this view is based mostly on electroencephalography (EEG) recordings that do not directly monitor neuronal synchronization of action potential firing. In this study, we used multielectrode single-unit recordings from the hippocampus to investigate firing of individual CA1 neurons and directly monitor synchronization of action potential firing between neurons during the different ictal phases of chemoconvulsant-induced epileptic seizures in vivo. During the early phase of seizures manifesting as low-amplitude rhythmic β-electrocorticography (ECoG) activity, the firing frequency of most neurons markedly increased. To our surprise, the average overall neuronal synchronization as measured by the cross-correlation function was reduced compared with control conditions with ∼60% of neuronal pairs showing no significant correlated firing. However, correlated firing was not uniform and a minority of neuronal pairs showed a high degree of correlated firing. Moreover, during the early phase of seizures, correlated firing between 9.8 ± 5.1% of all stably recorded pairs increased compared with control conditions. As seizures progressed and high-frequency ECoG polyspikes developed, the firing frequency of neurons further increased and enhanced correlated firing was observed between virtually all neuronal pairs. These findings indicated that epileptic seizures represented a hyperactive state with widespread increase in action potential firing. Hypersynchrony also characterized seizures. However, it initially developed in a small subset of neurons and gradually spread to involve the entire cortical network only in the later more intense ictal phases.

scholarly journals Temporal coupling of field potentials and action potentials in the neocortex

2017 ◽  
Author(s):  
Brendon O. Watson ◽  
Mingxin Ding ◽  
György Buzsáki
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Field Potential ◽  
Electromyographic Activity ◽  
Action Potential Firing ◽  
Firing Rates ◽  
Potential Firing ◽  
Temporal Coupling ◽  
Potential Activity ◽  
The Relationship

AbstractThe local field potential (LFP) is an aggregate measure of group neuronal activity and is often correlated with the action potentials of single neurons. In recent years investigators have found that action potential firing rates increase during elevations in power high-frequency band oscillations (50-200 Hz range). However action potentials also contribute to the LFP signal itself, making the spike–LFP relationship complex. Here we examine the relationship between spike rates and LFPs in varying frequency bands in rat neocortical recordings. We find that 50-180Hz oscillations correlate most consistently with high firing rates, but that other LFPs bands also carry information relating to spiking, including in some cases anti-correlations. Relatedly, we find that spiking itself and electromyographic activity contribute to LFP power in these bands. The relationship between spike rates and LFP power varies between brain states and between individual cells. Finally, we create an improved oscillation-based predictor of action potential activity by specifically utilizing information from across the entire recorded frequency spectrum of LFP. The findings illustrate both caveats and improvements to be taken into account in attempts to infer spiking activity from LFP.

Propofol and Sevoflurane Depress Spinal Neurons In Vitro via  Different Molecular Targets

2004 ◽  
Vol 101 (5) ◽  
pp. 1167-1176 ◽  
Author(s):  
Christian Grasshoff ◽  
Bernd Antkowiak
Keyword(s):  
Spinal Cord ◽  
Action Potential ◽  
Gabaa Receptors ◽  
Molecular Targets ◽  
Glycine Receptors ◽  
Spinal Neurons ◽  
Action Potential Firing ◽  
Spontaneous Action Potential ◽  
Potential Firing ◽  
Spontaneous Action

Background The capacity of general anesthetics to produce immobility is primarily spinally mediated. Recently, compelling evidence has been provided that the spinal actions of propofol involve gamma-aminobutyric acid type A (GABAA) receptors, whereas the contribution of glycine receptors remains uncertain. The relevant molecular targets of the commonly used volatile anesthetic sevoflurane in the spinal cord are largely unknown, but indirect evidence suggests a mechanism of action distinct from propofol. Methods The effects of sevoflurane and propofol on spontaneous action potential firing were investigated by extracellular voltage recordings from ventral horn interneurons in cultured spinal cord tissue slices obtained from embryonic rats (embryonic days 14-15). Results Propofol and sevoflurane reduced spontaneous action potential firing of neurons. Concentrations causing half-maximal effects (0.11 microm propofol, 0.11 mm sevoflurane) were lower than the median effective concentration immobility (1-1.5 microm propofol, 0.35 mm sevoflurane). At higher concentrations, complete inhibition of action potential activity was observed with sevoflurane but not with propofol. Effects of sevoflurane were mediated predominantly by glycine receptors (45%) and GABAA receptors (38%), whereas propofol acted almost exclusively via GABAA receptors (96%). Conclusions The authors' results suggest that glycine and GABAA receptors are the most important molecular targets mediating depressant effects of sevoflurane in the spinal cord. They provide evidence that sevoflurane causes immobility by a mechanism distinct from the actions of the intravenous anesthetic propofol. The finding that propofol acts exclusively via GABAA receptors can explain its limited capacity to depress spinal neurons in the authors' study.

CA3 neuron excitation and epileptiform discharge are sensitive to osmolality

1993 ◽  
Vol 69 (6) ◽  
pp. 2200-2208 ◽  
Author(s):  
V. Saly ◽  
R. D. Andrew
Keyword(s):  
Action Potential ◽  
Cortical Neurons ◽  
Hippocampal Slices ◽  
Clinical Signs ◽  
Field Potential ◽  
Mossy Fibers ◽  
Excitatory Postsynaptic Potential ◽  
Epsp Amplitude ◽  
Postsynaptic Potential ◽  
Ca3 Neurons

1. The clinical signs of rapidly developing overhydration commonly include generalized tonic-clonic seizure, which can be combatted by raising plasma osmolality. How cortical neurons respond to osmotic imbalance has been addressed only recently. In the CA3 cell region of hippocampal slices, lowered osmolality (-40 mOsm) rapidly swelled cells, increasing field potential amplitude over a period of 8 min and thereby elevating field effects and associated neuronal synchronization. 2. Over a longer time course (10-30 min), spontaneous excitatory postsynaptic potential (EPSP) amplitude gradually increased in 7 of 10 CA3 neurons recorded intracellularly. In nine additional CA3 cells, hyposmolality gradually induced combinations of action potential discharge, endogenous bursting, and increased synchronized synaptic input. All of these effects reversed in normosmotic ACSF. 3. Hyperosmotic artificial cerebrospinal fluid (ACSF) using mannitol reduced field potentials and dramatically lowered CA3 excitability by reducing spontaneous EPSP amplitude and associated bursting. Again, the gradual onset (10-30 min) of changes in spontaneous EPSP amplitude appeared independent of field potential changes, which were already maximal by 8 min. 4. Cutting mossy fibers did not affect the excitability changes induced by osmotic stress noted above. The EPSP/inhibitory postsynaptic potential (IPSP) sequence evoked from mossy fibers or stratum oriens was unaltered by osmotic change and so did not represent osmosensitive afferent input to CA3 neurons. Furthermore, as measured at the soma, resting membrane potential, cell input resistance, and the action potential threshold were unchanged in all cells. It followed that, because the CA3 neurons themselves were not responsive, a recurrent excitatory pathway could not represent the osmosensitive input.(ABSTRACT TRUNCATED AT 250 WORDS)

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