Dynamic Properties of Corticothalamic Neurons and Local Cortical Interneurons Generating Fast Rhythmic (30–40 Hz) Spike Bursts

1998 ◽  
Vol 79 (1) ◽  
pp. 483-490 ◽  
Author(s):  
Mircea Steriade ◽  
Igor Timofeev ◽  
Niklaus Dürmüller ◽  
François Grenier
Keyword(s):  
Cortical Neurons ◽  
Dynamic Properties ◽  
Synaptic Activity ◽  
Cortical Layers ◽  
Electrophysiological Properties ◽  
Cortical Interneurons ◽  
Cell Depolarization ◽  
Spike Bursts ◽  
40 Hz

Steriade, Mircea, Igor Timofeev, Niklaus Dürmüller, and François Grenier. Dynamic properties of corticothalamic neurons and local cortical interneurons generating fast rhythmic (30–40 Hz) spike-bursts. J. Neurophysiol. 79: 483–490, 1998. Fast spontaneous oscillations (mainly 30–40 Hz) characterize cortical and thalamic neuronal networks during behavioral states of increased vigilance and depend on cell depolarization under the influence of ascending activating systems. We investigated, by means of intracellular recording and staining in vivo, the properties of fast-oscillating cortical neurons from cat's motor and association areas, some projecting to the thalamus, others with locally arborizing axons. At a given level of depolarization, 28% of our neuronal sample discharged high-frequency spike bursts (300–600 Hz) that recurred rhythmically between 20 and 50 Hz. Such fast rhythmic bursting neurons have been found in both superficial and deep cortical layers. Slight changes in membrane potential as well as synaptic activity in thalamocortical networks dramatically altered the discharge patterns, from single spikes to rhythmic spike-bursts, and eventually to fast tonic firing without frequency adaptation. Thus our data challenge the conventional idea that sharply defined, invariant features and distinct locations in certain cortical layers characterize some neocortical cell-classes. We demonstrate that the distinctions between intrinsic electrophysiological properties of neocortical neurons are much more labile than conventionally thought. The present results, which indicate that corticothalamic neurons discharge fast rhythmic spike bursts mainly at 30–40 Hz, suggest that this activity results in integrated fast oscillations within corticothalamic networks.

Characterization of Synaptic Conductances and Integrative Properties During Electrically Induced EEG-Activated States in Neocortical Neurons In Vivo

2005 ◽  
Vol 94 (4) ◽  
pp. 2805-2821 ◽  
Author(s):  
Michael Rudolph ◽  
Joe Guillaume Pelletier ◽  
Denis Paré ◽  
Alain Destexhe
Keyword(s):  
Cortical Neurons ◽  
Computational Models ◽  
Input Resistance ◽  
Synaptic Activity ◽  
Intracellular Recordings ◽  
Neocortical Neurons ◽  
Up States ◽  
Conductance State ◽  
Stimulation Of

The activation of the electroencephalogram (EEG) is paralleled with an increase in the firing rate of cortical neurons, but little is known concerning the conductance state of their membrane and its impact on their integrative properties. Here, we combined in vivo intracellular recordings with computational models to investigate EEG-activated states induced by stimulation of the brain stem ascending arousal system. Electrical stimulation of the pedonculopontine tegmental (PPT) nucleus produced long-lasting (≈20 s) periods of desynchronized EEG activity similar to the EEG of awake animals. Intracellularly, PPT stimulation locked the membrane into a depolarized state, similar to the up-states seen during deep anesthesia. During these EEG-activated states, however, the input resistance was higher than that during up-states. Conductance measurements were performed using different methods, which all indicate that EEG-activated states were associated with a synaptic activity dominated by inhibitory conductances. These results were confirmed by computational models of reconstructed pyramidal neurons constrained by the corresponding intracellular recordings. These models indicate that, during EEG-activated states, neocortical neurons are in a high-conductance state consistent with a stochastic integrative mode. The amplitude and timing of somatic excitatory postsynaptic potentials were nearly independent of the position of the synapses in dendrites, suggesting that EEG-activated states are compatible with coding paradigms involving the precise timing of synaptic events.

scholarly journals Dopamine modulates the integrity of the perisynaptic extracellular matrix at excitatory synapses

2019 ◽  
Author(s):  
Jessica Mitlöhner ◽  
Rahul Kaushik ◽  
Hartmut Niekisch ◽  
Armand Blondiaux ◽  
Christine E. Gee ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cortical Neurons ◽  
Receptor Activation ◽  
Synaptic Activity ◽  
Excitatory Synapses ◽  
Intracellular Calcium Signaling ◽  
Rat Cortical Neurons ◽  
Synaptic Receptors

SummaryIn the brain, Hebbian-type and homeostatic forms of plasticity are affected by neuromodulators like dopamine (DA). Modifications of the perisynaptic extracellular matrix (ECM), controlling functions and mobility of synaptic receptors as well as diffusion of transmitters and neuromodulators in the extracellular space, are crucial for the manifestation of plasticity. Mechanistic links between synaptic activation and ECM modifications are largely unknown. Here, we report that neuromodulation via D1-type DA receptors can induce targeted ECM proteolysis specifically at excitatory synapses of rat cortical neurons via proteases ADAMTS-4 and -5. We show that receptor activation induces increased proteolysis of brevican (BC) and aggrecan, two major constituents of the adult ECM, in vivo and in vitro. ADAMTS immunoreactivity is detected near synapses, and shRNA-mediated knockdown reduced BC cleavage. We outline a molecular scenario how synaptic activity and neuromodulation are linked to ECM rearrangements via increased cAMP levels, NMDA receptor activation, and intracellular calcium signaling.

scholarly journals KCC2 overexpression prevents the paradoxical seizure-promoting action of somatic inhibition

2018 ◽  
Author(s):  
Vincent Magloire ◽  
Jonathan Cornford ◽  
Andreas Lieb ◽  
Dimitri M. Kullmann ◽  
Ivan Pavlov
Keyword(s):  
Potassium Chloride ◽  
Cortical Neurons ◽  
Closed Loop ◽  
Network Activity ◽  
Intracellular Chloride ◽  
Cortical Interneurons ◽  
The Face ◽  
Somatic Inhibition

AbstractAlthough cortical interneurons are apparently well-placed to suppress seizures, several recent reports have highlighted a paradoxical role of parvalbumin-positive perisomatic-targeting (PV+) interneurons in ictogenesis. Here, we use an acute in vivo model of focal cortical seizures in awake behaving mice, together with closed-loop optogenetic manipulation of PV+ interneurons, to investigate their function during seizures. We show that photo-depolarization of PV+ interneurons rapidly switches from an anti-ictal to a pro-ictal effect within a few seconds of seizure initiation. The pro-ictal effect of delayed photostimulation of PV+ interneurons was not shared with dendrite-targeting somatostatin-positive (SOM+) interneurons. We also show that this switch can be prevented by overexpression of the neuronal potassium-chloride co-transporter KCC2 in principal cortical neurons. These results suggest that strategies aimed at improving the ability of principal neurons to maintain intracellular chloride levels in the face of excessive network activity can prevent interneurons from contributing to seizure perpetuation.

scholarly journals 0017 Transmembrane TNF- Soluble TNF Receptor Reverse Signal to Induce a Wake-Like State in Vitro

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A7-A7
Author(s):  
C J Dykstra-Aiello ◽  
K Koh ◽  
J Nguyen ◽  
J M Krueger
Keyword(s):  
Cortical Neurons ◽  
Action Potentials ◽  
State Regulation ◽  
Electrode Arrays ◽  
Electrophysiological Properties ◽  
Reverse Signaling ◽  
Soluble Tnf Receptor ◽  
Induced Changes

Abstract Introduction Tumor necrosis factor (TNF) has sleep regulatory roles. Neuronal action potentials enhance TNF expression. Neuron/glia co-cultures exhibit more intense local sleep-like states after TNF administration in vitro. Both TNF and TNF receptors (Rs) are produced as transmembrane (tm) proteins that can subsequently be cleaved to produce soluble (s) forms. With immunocytes, sTNFR can bind tmTNF and induce reverse signaling within the cell expressing the tmTNF. This is opposite of conventional signaling induced by soluble ligands (e.g. sTNF) binding to transmembrane receptors. Having previously shown sleep inhibition after sTNFR administration in vivo, we hypothesized that tmTNF-sTNFR binding would induce wake-like states in vitro through reverse signaling. Methods Somatosensory cortical neurons/glia, from wildtype (WT) mice and mice lacking either TNF (TNF-KO) or both TNFRs (TNFR-KO), were co-cultured on multi-electrode arrays. Daily one-hour recordings were taken consecutively on incubation days 4 - 13 for development analyses. On day 14, a one-hour baseline was recorded prior to treatment with sTNFR (0.0 ng/μL-120 ng/μL). Immediately after treatment, recordings resumed for one hour. Synchronization of electrical activity (SYN), action potentials, slow wave power (SWP; 0.25–3.75 Hz), and burstiness index (measures used to define sleep in vivo) were used to characterize the ontological emergence of these electrophysiological properties and sTNFR-induced changes in vitro. Results Development rates were reduced in TNF-KO cells and increased in TNFR-KO cells relative to each other and to WT mice. Additionally, after sTNFR treatments, cells from TNFR-KO mice, which still express TNF, exhibited dose-dependent decreased SYN and SWP, indicative of a wake-like state. In contrast, cells from TNF-KO mice lacked a response to sTNFR treatment. Conclusion To our knowledge, this is the first demonstration of reverse TNF signaling with respect to sleep/wake states. As such, it provides a new way of viewing state regulation and associated potential clinical applications. Support This work was supported by grant NS096250 awarded to JK by NIH/NINDS.

scholarly journals Impact of Network Activities on Neuronal Properties in Corticothalamic Systems

2001 ◽  
Vol 86 (1) ◽  
pp. 1-39 ◽  
Author(s):  
M. Steriade
Keyword(s):  
Membrane Potential ◽  
Cortical Neurons ◽  
Cortical Cell ◽  
Input Resistance ◽  
Synaptic Activity ◽  
Brain Functions ◽  
Intact Brain ◽  
Intact Cortex

Data from in vivo and in vitro experiments are discussed to emphasize that synaptic activities in neocortex and thalamus have a decisive impact on intrinsic neuronal properties in intact-brain preparations under anesthesia and even more so during natural states of vigilance. Thus the firing patterns of cortical neuronal types are not inflexible but may change with the level of membrane potential and during periods rich in synaptic activity. The incidences of some cortical cell classes (defined by their responses to depolarizing current pulses) are different in isolated cortical slabs in vivo or in slices maintained in vitro compared with the intact cortex of naturally awake animals. Network activities, which include the actions of generalized modulatory systems, have a profound influence on the membrane potential, apparent input resistance, and backpropagation of action potentials. The analysis of various oscillatory types leads to the conclusion that in the intact brain, there are no “pure” rhythms, generated in simple circuits, but complex wave sequences (consisting of different, low- and fast-frequency oscillations) that result from synaptic interactions in corticocortical and corticothalamic neuronal loops under the control of activating systems arising in the brain stem core or forebrain structures. As an illustration, it is shown that the neocortex governs the synchronization of network or intrinsically generated oscillations in the thalamus. The rhythmic recurrence of spike bursts and spike trains fired by thalamic and cortical neurons during states of decreased vigilance may lead to plasticity processes in neocortical neurons. If these phenomena, which may contribute to the consolidation of memory traces, are not constrained by inhibitory processes, they induce seizures in which the neocortex initiates the paroxysms and controls their thalamic reflection. The results indicate that intact-brain preparations are necessary to investigate global brain functions such as behavioral states of vigilance and paroxysmal activities.

Cellular Mechanisms Underlying Intrathalamic Augmenting Responses of Reticular and Relay Neurons

1998 ◽  
Vol 79 (5) ◽  
pp. 2716-2729 ◽  
Author(s):  
Igor Timofeev ◽  
Mircea Steriade
Keyword(s):  
Cortical Neurons ◽  
Oscillatory Activity ◽  
High Threshold ◽  
Intracellular Recordings ◽  
Thalamic Nuclei ◽  
Cellular Mechanisms ◽  
Discharge Patterns ◽  
Spike Bursts ◽  
Relay Neurons

Timofeev, Igor and Mircea Steriade. Cellular mechanisms underlying intrathalamic augmenting responses of reticular and relay neurons. J. Neurophysiol. 79: 2716–2729, 1998. Augmenting (or incremental) responses are progressively growing potentials elicited by 5- to 15-Hz stimulation within the thalamus, cerebral cortex, or by setting into action reciprocal thalamocortical neuronal loops. These responses are associated with short-term plasticity processes in thalamic and cortical neurons. In the present study, in vivo intracellular recordings of thalamic reticular (RE) and thalamocortical (TC), as well as dual intracellular recordings, were used to explore the mechanisms of two types of intrathalamic augmenting responses elicited by thalamic stimuli at 10 Hz in decorticated cats. As recently described, after decortication, TC cells display incremental burst responses to thalamic stimuli that occur through either progressive depolarization (high threshold, HT) or progressive hyperpolarization leading to deinactivation of low-threshold (LT) spike bursts. Here, low-intensity stimuli (10 Hz) to dorsal thalamic nuclei elicited decremental responses in GABAergic RE cells, consisting of a progressive diminution in the number of action potentials in successive spike bursts, whereas higher stimulation (>50% of maximal strength) induced augmentation characterized by an increased number of spikes in repetitive responses. These opposing discharge patterns occurred in the absence of changes in the membrane potential of RE cells. In TC cells, augmentation depended on the thalamic site where testing volleys were applied. With stimuli applied closer to the site of impalement, augmenting resulted from a transformation from LT spike bursts into HT responses. Augmenting responses were followed by self-sustained oscillatory activity, within the frequency of spindles (7–14 Hz) or clock-like delta oscillation (1–4 Hz). As LT augmentation in TC cells results from their progressive hyperpolarization, we tested the effects exerted by the activating depolarizing system arising in the mesopontine cholinergic nuclei and found that such conditioning pulse-trains prevented the hyperpolarizing-rebound sequences as well as the LT augmenting in TC cells. We propose that the depolarization-dependent (HT) augmenting responses in TC cells result from decremental responses in RE neurons that are due to intra-RE inhibitory processes leading to disinhibition in target TC neurons, whereas LT-type augmenting in TC cells is produced mainly by incremental responses in GABAergic RE neurons.

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.

Membrane Capacitance of Cortical Neurons and Glia During Sleep Oscillations and Spike-Wave Seizures

1999 ◽  
Vol 82 (5) ◽  
pp. 2731-2746 ◽  
Author(s):  
Florin Amzica ◽  
Dag Neckelmann
Keyword(s):  
Glial Cells ◽  
Cortical Neurons ◽  
Membrane Surface ◽  
Cell Types ◽  
Membrane Capacitance ◽  
Synaptic Activity ◽  
Neuronal Membrane ◽  
Membrane Potential Oscillation ◽  
Spike Wave

Dual intracellular recordings in vivo were used to disclose relationships between cortical neurons and glia during spontaneous slow (<1 Hz) sleep oscillations and spike-wave (SW) seizures in cat. Glial cells displayed a slow membrane potential oscillation (<1 Hz), in close synchrony with cortical neurons. In glia, each cycle of this oscillation was made of a round depolarizing potential of 1.5–3 mV. The depolarizing slope corresponded to a steady depolarization and sustained synaptic activity in neurons (duration, 0.5–0.8 s). The repolarization of the glial membrane (duration, 0.5–0.8 s) coincided with neuronal hyperpolarization, associated with disfacilitation, and suppressed synaptic activity in cortical networks. SW seizures in glial cells displayed phasic events, synchronized with neuronal paroxysmal potentials, superimposed on a plateau of depolarization, that lasted for the duration of the seizure. Measurements of the neuronal membrane capacitance during slow oscillating patterns showed small fluctuations around the resting values in relation to the phases of the slow oscillation. In contrast, the glial capacitance displayed a small-amplitude oscillation of 1–2 Hz, independent of phasic sleep and seizure activity. Additionally, in both cell types, SW seizures were associated with a modulatory, slower oscillation (≈0.2 Hz) and a persistent increase of capacitance, developing in parallel with the progression of the seizure. These capacitance variations were dependent on the severity of the seizure and the distance between the presumed seizure focus and the recording site. We suggest that the capacitance variations may reflect changes in the membrane surface area (swelling) and/or of the interglial communication via gap junctions, which may affect the synchronization and propagation of paroxysmal activities.

Impact of Spontaneous Synaptic Activity on the Resting Properties of Cat Neocortical Pyramidal Neurons In Vivo

1998 ◽  
Vol 79 (3) ◽  
pp. 1450-1460 ◽  
Author(s):  
Denis Paré ◽  
Eric Shink ◽  
Hélène Gaudreau ◽  
Alain Destexhe ◽  
Eric J. Lang
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Synaptic Activity ◽  
Intact Brain ◽  
Lower Temperature ◽  
The Impact ◽  
Neocortical Pyramidal Neurons

Paré, Denis, Eric Shink, Hélène Gaudreau, Alain Destexhe, and Eric J. Lang. Impact of spontaneous synaptic activity on the resting properties of cat neocortical pyramidal neurons in vivo. J. Neurophysiol. 79: 1450–1460, 1998. The frequency of spontaneous synaptic events in vitro is probably lower than in vivo because of the reduced synaptic connectivity present in cortical slices and the lower temperature used during in vitro experiments. Because this reduction in background synaptic activity could modify the integrative properties of cortical neurons, we compared the impact of spontaneous synaptic events on the resting properties of intracellularly recorded pyramidal neurons in vivo and in vitro by blocking synaptic transmission with tetrodotoxin (TTX). The amount of synaptic activity was much lower in brain slices (at 34°C), as the standard deviation of the intracellular signal was 10–17 times lower in vitro than in vivo. Input resistances ( R ins) measured in vivo during relatively quiescent epochs (“control R ins”) could be reduced by up to 70% during periods of intense spontaneous activity. Further, the control R ins were increased by ∼30–70% after TTX application in vivo, approaching in vitro values. In contrast, TTX produced negligible R in changes in vitro (∼4%). These results indicate that, compared with the in vitro situation, the background synaptic activity present in intact networks dramatically reduces the electrical compactness of cortical neurons and modifies their integrative properties. The impact of the spontaneous synaptic bombardment should be taken into account when extrapolating in vitro findings to the intact brain.

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