Intracellular Study of Excitability in the Seizure-Prone Neocortex In Vivo

1999 ◽  
Vol 82 (6) ◽  
pp. 3108-3122 ◽  
Author(s):  
Mircea Steriade ◽  
Florin Amzica
Keyword(s):  
Cortical Neurons ◽  
Control Period ◽  
Resting Membrane Potential ◽  
Postsynaptic Potentials ◽  
Inhibitory Postsynaptic Potentials ◽  
Neocortical Neurons ◽  
Slow Sleep ◽  
Intracellular Study ◽  
Spike Wave

The excitability of neocortical neurons from cat association areas 5–7 was investigated during spontaneously occurring seizures with spike-wave (SW) complexes at 2–3 Hz. We tested the antidromic and orthodromic responsiveness of neocortical neurons during the “spike” and “wave” components of SW complexes, and we placed emphasis on the dynamics of excitability changes from sleeplike patterns to seizures. At the resting membrane potential, an overwhelming majority of neurons displayed seizures over a depolarizing envelope. Cortical as well as thalamic stimuli triggered isolated paroxysmal depolarizing shifts (PDSs) that eventually developed into SW seizures. PDSs could also be elicited by cortical or thalamic volleys during the wave-related hyperpolarization of neurons, but not during the spike-related depolarization. The latencies of evoked excitatory postsynaptic potentials (EPSPs) progressively decreased, and their slope and depolarization surface increased, from the control period preceding the seizure to the climax of paroxysm. Before the occurrence of full-blown seizures, thalamic stimuli evoked PDSs arising from the postinhibitory rebound excitation, whereas cortical stimuli triggered PDSs immediately after the early EPSP. These data shed light on the differential excitability of cortical neurons during the spike and wave components of SW seizures, and on the differential effects of cortical and thalamic volleys leading to such paroxysms. We conclude that the wave-related hyperpolarization does not represent GABA-mediated inhibitory postsynaptic potentials (IPSPs), and we suggest that it is a mixture of disfacilitation and Ca2+-dependent K+ currents, similar to the prolonged hyperpolarization of the slow sleep oscillation.

Synaptic Interactions Between Thalamic and Cortical Inputs Onto Cortical Neurons In Vivo

2004 ◽  
Vol 91 (5) ◽  
pp. 1990-1998 ◽  
Author(s):  
Pablo Fuentealba ◽  
Sylvain Crochet ◽  
Igor Timofeev ◽  
Mircea Steriade
Keyword(s):  
Cortical Neurons ◽  
Time Course ◽  
Input Resistance ◽  
Maximal Effect ◽  
Time Intervals ◽  
Neocortical Neurons ◽  
Synaptic Interactions ◽  
Cortical Responses ◽  
Cortical Inputs

To study the interactions between thalamic and cortical inputs onto neocortical neurons, we used paired-pulse stimulation (PPS) of thalamic and cortical inputs as well as PPS of two cortical or two thalamic inputs that converged, at different time intervals, onto intracellularly recorded cortical and thalamocortical neurons in anesthetized cats. PPS of homosynaptic cortico-cortical pathways produced facilitation, depression, or no significant effects in cortical pathways, whereas cortical responses to thalamocortical inputs were mostly facilitated at both short and long intervals. By contrast, heterosynaptic interactions between either cortical and thalamic, or thalamic and cortical, inputs generally produced decreases in the peak amplitudes and depolarization area of evoked excitatory postsynaptic potentials (EPSPs), with maximal effect at ∼10 ms and lasting from 60 to 100 ms. All neurons tested with thalamic followed by cortical stimuli showed a decrease in the apparent input resistance ( Rin), the time course of which paralleled that of decreased responses, suggesting that shunting is the factor accounting for EPSP's decrease. Only half of neurons tested with cortical followed by thalamic stimuli displayed changes in Rin. Spike shunting in the thalamus may account for those cases in which decreased synaptic responsiveness of cortical neurons was not associated with decreased Rin because thalamocortical neurons showed decreased firing probability during cortical stimulation. These results suggest a short-lasting but strong shunting between thalamocortical and cortical inputs onto cortical neurons.

Absence of a Prevalent Laminar Distribution of IPSPs in Association Cortical Neurons of Cat

1997 ◽  
Vol 78 (5) ◽  
pp. 2742-2753 ◽  
Author(s):  
Diego Contreras ◽  
Niklaus Dürmüller ◽  
Mircea Steriade
Keyword(s):  
Cortical Neurons ◽  
Feedback Inhibition ◽  
Anterior Part ◽  
Cortical Stimulation ◽  
Association Cortex ◽  
Postsynaptic Potentials ◽  
Thalamic Stimulation ◽  
Laminar Distribution ◽  
Deep Layers

Contreras, Diego, Niklaus Dürmüller, and Mircea Steriade. Absence of a prevalent laminar distribution of IPSPs in association cortical neurons of cat. J. Neurophysiol. 78: 2742–2753, 1997. The depth distribution of inhibitory postsynaptic potentials (IPSPs) was studied in cat suprasylvian (association) cortex in vivo. Single and dual simultaneous intracellular recordings from cortical neurons were performed in the anterior part of suprasylvian gyrus (area 5). Synaptic responses were obtained by stimulating the suprasylvian cortex, 2–3 mm anterior to the recording site, as well as the thalamic lateral posterior (LP) nucleus. Neurons were recorded from layers 2 to 6 and were classified as regular spiking (RS, n = 132), intrinsically bursting (IB, n = 24), and fast spiking (FS, n = 4). Most IB cells were located in deep layers (below 0.7 mm, n = 19), but we also found some IB cells more superficially (between 0.2 and 0.5 mm, n = 5). Deeply lying corticothalamic neurons were identified by their antidromic invasion on thalamic stimulation. Neurons responded with a combination of excitatory postsynaptic potentials (EPSPs) and IPSPs to both cortical and thalamic stimulation. No consistent relation was found between cell type or cell depth and the amplitude or duration of the IPSPs. In response to thalamic stimulation, RS cells had IPSPs of 7.9 ± 0.9 (SE) mV amplitude and 88.9 ± 6.4 ms duration. In IB cells, IPSPs elicited by thalamic stimulation had 7.4 ± 1.3 mV amplitude and 84.7 ± 14.3 ms duration. The differences between the two (RS and IB) groups were not statistically significant. Compared with thalamically elicited inhibitory responses, cortical stimulation evoked IPSPs with higher amplitude (12.3 ± 1.7 mV) and longer duration (117 ± 17.3 ms) at all depths. Both cortically and thalamically evoked IPSPs were predominantly monophasic. Injections of Cl− fully reversed thalamically as well as cortically evoked IPSPs and revealed additional late synaptic components in response to cortical stimulation. These data show that the amount of feed forward and feedback inhibition to cat's cortical association cells is not orderly distributed to distinct layers. Thus local cortical microcircuitry goes beyond the simplified structure determined by cortical layers.

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.

Monosynaptic inhibitory postsynaptic potentials of cortical neurons

1976 ◽  
Vol 7 (5) ◽  
pp. 351-358
Author(s):  
F. N. Serkov ◽  
E. Sh. Yanovskii ◽  
A. N. Tal'nov
Keyword(s):  
Cortical Neurons ◽  
Postsynaptic Potentials ◽  
Inhibitory Postsynaptic Potentials

Dynamics of the orientation tuning of postsynaptic potentials in the cat visual cortex

1995 ◽  
Vol 12 (4) ◽  
pp. 621-628 ◽  
Author(s):  
M. Volgushev ◽  
T.R. Vidyasagar ◽  
Xing Pei
Keyword(s):  
Cortical Neurons ◽  
Stimulus Presentation ◽  
Stimulus Onset ◽  
Temporal Coding ◽  
Orientation Tuning ◽  
Integration Time ◽  
Cortical Cells ◽  
Postsynaptic Potentials ◽  
Temporal Windows

AbstractWe evaluated the dynamic aspects of the orientation tuning of the input to cat visual cortical neurons by analyzing the postsynaptic potentials (PSPs) evoked by flashing bars of light. The PSPs were recorded using in vivo whole-cell technique, and we analyzed the orientation tuning during subsequent temporal windows after stimulus onset and offset. Our results show that the amplitudes of the postsynaptic potential are reliably tuned to orientation and matching that of the spike responses only during certain temporal windows. During the first 100 ms after stimulus presentation, orientation tuning of the membrane potential underwent regular changes. Within particular intervals, orientation tuning of the input was much sharper than that estimated according to the whole response. In most cells, optimal orientation was usually stable over the whole period. In several cells which had a second hump of EPSPs in the response, this second hump was tuned to the same orientation as the first one, but always showed sharper tuning. Estimation of the integration time revealed sufficient delay between the appearance of EPSPs and spikes, to let inhibition influence spike generation. These results show that orientation selectivity of the input to cortical cells is a dynamic function, and also indicate the possibility of temporal coding in the visual system.

scholarly journals Dynamic Interactions Determine Partial Thalamic Quiescence in a Computer Network Model of Spike-and-Wave Seizures

1997 ◽  
Vol 77 (4) ◽  
pp. 1679-1696 ◽  
Author(s):  
William W. Lytton ◽  
Diego Contreras ◽  
Alain Destexhe ◽  
Mircea Steriade
Keyword(s):  
Network Model ◽  
Cortical Neurons ◽  
Computer Network ◽  
Spatial Inhomogeneity ◽  
Neuron Activity ◽  
Inhibitory Input ◽  
Dynamic Interactions ◽  
Low Threshold ◽  
Spike Wave

Lytton, William W., Diego Contreras, Alain Destexhe, and Mircea Steriade. Dynamic interactions determine partial thalamic quiescence in a computer network model of spike-and-wave seizures. J. Neurophysiol. 77: 1679–1696, 1997. In vivo intracellular recording from cat thalamus and cortex was performed during spontaneous spike-wave seizures characterized by synchronously firing cortical neurons correlated with the electroencephalogram. During these seizures, thalamic reticular (RE) neurons discharged with long spike bursts riding on a depolarization, whereas thalamocortical (TC) neurons were either entrained into the seizures (40%) or were quiescent (60%). During quiescence, TC neurons showed phasic inhibitory postsynaptic potentials (IPSPs) that coincided with paroxysmal depolarizing shifts in the simultaneously recorded cortical neuron. Computer simulations of a reciprocally connected TC-RE pair showed two major modes of TC-RE interaction. In one mode, a mutual oscillation involved direct TC neuron excitation of the RE neuron leading to a burst that fed back an IPSP into the TC neuron, producing a low-threshold spike. In the other, quiescent mode, the TC neuron was subject to stronger coalescing IPSPs. Simulated cortical stimulation could trigger a transition between the two modes. This transition could go in either direction and was dependent on the precise timing of the input. The transition did not always follow the stimulation immediately. A larger, multicolumnar simulation was set up to assess the role of the TC-RE pair in the context of extensive divergence and convergence. The amount of TC neuron spiking generally correlated with the strength of total inhibitory input, but large variations in the amount of spiking could be seen. Evidence for mutual oscillation could be demonstrated by comparing TC neuron firing with that in reciprocally connected RE neurons. An additional mechanism for TC neuron quiescence was assessed with the use of a cooperative model of γ-aminobutyric acid-B (GABAB)-mediated responses. With this model, RE neurons receiving repeated strong excitatory input produced TC neuron quiescence due to burst-duration-associated augmentation of GABAB current. We predict the existence of spatial inhomogeneity in apparently generalized spike-wave seizures, involving a center-surround pattern. In the center, intense cortical and RE neuron activity would be associated with TC neuron quiescence. In the surround, less intense hyperpolarization of TC neurons would allow low-threshold spikes to occur. This surround, an “epileptic penumbra,” would be the forefront of the expanding epileptic wave during the process of initial seizure generalization. Therapeutically, we would then predict that agents that reduce TC neuron activity would have a greater effect on seizure onset than on ongoing spike-wave seizures or other thalamic oscillations.

scholarly journals Fast Rhythmic Bursting Can Be Induced in Layer 2/3 Cortical Neurons by Enhancing Persistent Na+ Conductance or by Blocking BK Channels

2003 ◽  
Vol 89 (2) ◽  
pp. 909-921 ◽  
Author(s):  
Roger D. Traub ◽  
Eberhard H. Buhl ◽  
Tengis Gloveli ◽  
Miles A. Whittington
Keyword(s):  
Cortical Neurons ◽  
Firing Pattern ◽  
Critical Role ◽  
Sensory Stimulation ◽  
Bk Channels ◽  
Bk Channel ◽  
Neocortical Neurons ◽  
Layer 2

Fast rhythmic bursting (or “chattering”) is a firing pattern exhibited by selected neocortical neurons in cats in vivo and in slices of adult ferret and cat brain. Fast rhythmic bursting (FRB) has been recorded in certain superficial and deep principal neurons and in aspiny presumed local circuit neurons; it can be evoked by depolarizing currents or by sensory stimulation and has been proposed to depend on a persistent g Na that causes spike depolarizing afterpotentials. We constructed a multicompartment 11-conductance model of a layer 2/3 pyramidal neuron, containing apical dendritic calcium-mediated electrogenesis; the model can switch between rhythmic spiking (RS) and FRB modes of firing, with various parameter changes. FRB in this model is favored by enhancing persistent g Na and also by measures that reduce [Ca2+]i or that reduce the conductance of g K(C) (a fast voltage- and Ca2+-dependent conductance). Axonal excitability plays a critical role in generating fast bursts in the model. In vitro experiments in rat layer 2/3 neurons confirmed (as shown previously by others) that RS firing could be switched to fast rhythmic bursting, either by buffering [Ca2+]i or by enhancing persistent g Na. In addition, our experiments confirmed the model prediction that reducing g KC (with iberiotoxin) would favor FRB. During the bursts, fast prepotentials (spikelets) could occur that did not originate in apical dendrites and that appear to derive from the axon. We suggest that modulator-induced regulation of [Ca2+] dynamics or of BK channel conductance, for example via protein kinase A, could play a role in determining the firing pattern of neocortical neurons; specifically, such modulation could play a role in regulating whether neurons respond to strong stimulation with fast rhythmic bursts.

Voltage dependence of excitatory postsynaptic potentials of rat neocortical neurons

1991 ◽  
Vol 65 (2) ◽  
pp. 371-382 ◽  
Author(s):  
R. A. Deisz ◽  
G. Fortin ◽  
W. Zieglgansberger
Keyword(s):  
Action Potentials ◽  
Inward Rectification ◽  
Resting Membrane Potential ◽  
Excitatory Postsynaptic Potentials ◽  
Postsynaptic Potentials ◽  
Electrode Current ◽  
Time Integral ◽  
Neocortical Neurons ◽  
Voltage Dependent

1. The properties of excitatory postsynaptic potentials (EPSPs) of rat neocortical neurons were investigated with a fast single-electrode current-voltage clamp in vitro. Typically, apparently pure EPSPs were obtained by selection of electric stimuli of low intensity. 2. The amplitude and time integral of the EPSP increased when the neuron was depolarized. At threshold for generation of action potentials, the amplitude of EPSPs was increased by approximately 30% [from 5.0 +/- 2.1 to 6.3 +/- 1.0 (SD) mV, n = 12]. The integral of EPSPs was maximally about fourfold (3.7 +/- 1.5, n = 16) larger than at resting membrane potential (Em). The mechanisms involved in this augmentation of EPSPs were further investigated. 3. The amplitude and the time integral of excitatory postsynaptic currents (EPSCs) decreased linearly with shifts in command potential from -100 to -60 mV. The decrease of the EPSC integral with depolarization indicates that the enhancement of the EPSP may be brought about by recruitment of a voltage-dependent inward current. 4. Evoking EPSPs at various delays after the onset of small depolarizing current pulses (0.3-0.6 nA, 600 ms) revealed that augmentation decays with time. The integral of EPSPs evoked approximately 80 ms after the onset of the current pulse was 3.7 (+/- 1.5, n = 16) times larger than at Em. The integral of EPSPs evoked at 480 ms. however, were only twofold (+/- 0.7, n = 16) larger. Hence EPSPs evoked after a delay of 80 ms were 1.7-fold (+/- 0.4, n = 24) larger than EPSPs evoked after 480 ms. EPSCs were independent of the delay of stimulation at all potentials. 5. Intracellular application of the lidocaine derivative N-(2,6-dimethyl-phenylcarbamoylmethyl) triethylammonium bromide (QX 314) at 100 mM from pipettes rapidly abolished fast action potentials and inward rectification. During comparable depolarizations the increase in EPSP integrals was much smaller in QX 314-treated neurons than in controls. On average, the integral of EPSPs evoked at 70-90 ms was 1.7 times (+/- 1.0) larger than at Em, and the integral of EPSPs evoked with larger delays was close to the value obtained at resting Em (0.9 +/- 0.3, n = 8). The ratio of EPSP integrals early versus late (1.8 +/- 0.5) is comparable to controls, suggesting that QX 314-sensitive currents are unlikely to be involved in the time-dependent enhancement. 6. Mimicking EPSPs by brief depolarizations atop long depolarizations revealed a time- and voltage-dependent enhancement comparable to that of EPSPs.(ABSTRACT TRUNCATED AT 400 WORDS)

Membrane Properties and Firing Patterns of Inferior Colliculus Neurons: An In Vivo Patch-Clamp Study in Rodents

2007 ◽  
Vol 98 (1) ◽  
pp. 443-453 ◽  
Author(s):  
M. L. Tan ◽  
H. P. Theeuwes ◽  
L. Feenstra ◽  
J.G.G. Borst
Keyword(s):  
Patch Clamp ◽  
Inferior Colliculus ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Firing Patterns ◽  
Postsynaptic Potentials ◽  
Whole Cell Patch Clamp ◽  
Auditory Nucleus ◽  
Clamp Study

The inferior colliculus (IC) is a large auditory nucleus in the midbrain, which is a nearly obligatory relay center for ascending auditory projections. We made in vivo whole cell patch-clamp recordings of IC cells in young-adult anesthetized C57/Bl6 mice and Wistar rats to characterize their membrane properties and spontaneous inputs. We observed spikelets in both rat (18%) and mouse (13%) IC neurons, suggesting that IC neurons may be connected by electrical synapses. In many cells, spontaneous postsynaptic potentials were sufficiently large to contribute to spike irregularity. Cells differed considerably in the number of simultaneous spontaneous postsynaptic potentials that would be needed to trigger an action potential. Depolarizing and hyperpolarizing current injections showed six different types of firing patterns: buildup, accelerating, burst-onset, burst-sustained, sustained, and accommodating. Their relative frequencies were similar in both species. In mice, about half of the cells showed a clear depolarizing sag, suggesting that they have the hyperpolarization-activated current Ih. This sag was observed more often in burst and in accommodating cells than in buildup, accelerating, or sustained neurons. Cells with Ih had a significantly more depolarized resting membrane potential. They were more likely to fire rebound spikes and generally showed long-lasting afterhyperpolarizations following long depolarizations. We therefore suggest a separate functional role for Ih.

Electrophysiology of cat association cortical cells in vivo: intrinsic properties and synaptic responses

1993 ◽  
Vol 70 (1) ◽  
pp. 418-430 ◽  
Author(s):  
A. Nunez ◽  
F. Amzica ◽  
M. Steriade
Keyword(s):  
Action Potential ◽  
Cortical Neurons ◽  
Secondary Component ◽  
Intrinsic Properties ◽  
Postsynaptic Potentials ◽  
Current Pulses ◽  
Contralateral Cortex ◽  
Stimulation Of ◽  
Synaptic Responses

1. The intrinsic properties and synaptic responses of association cortical neurons (n = 179) recorded from cat's areas 5 and 7 were studied in vivo. Intracellular recordings were performed under urethane anesthesia. Resting membrane potential (Vm) was -71.7 +/- 1.2 (SE) mV, amplitude of action potential was 83.7 +/- 2.3 mV, and input resistance was 18.4 +/- 1.8 M omega. Cells were identified ortho- and antidromically from lateroposterior and centrolateral thalamic nuclei and from homotopic foci in the contralateral cortex. Physiologically identified neurons were intracellularly stained with Lucifer yellow (LY) and found to be pyramidal-shaped elements (n = 21). 2. We classified the neurons as regular-spiking and intrinsically bursting cells. Regular-spiking cells were further classified as slow- and fast-adapting according to the adaptation of spike frequency during long-lasting depolarizing current pulses. 3. Regular-spiking, slow-adapting neurons had a monophasic afterhyperpolarization (AHP) or a biphasic AHP with fast and medium components (FAHP, mAHP). Slow-adapting behavior was observed in 84% (n = 119) of the regular-spiking cells. 4. Regular-spiking, fast-adapting cells only fired a train of spikes at the beginning of the pulse. Thereafter, the Vm remained as a depolarizing plateau, occasionally triggering some spikes. These neurons had a monophasic AHP and represented 16% (n = 23) of the regular-spiking neurons. 5. Intrinsically bursting neurons (n = 37) were observed in 20% of neocortical cells at depolarized Vm. Their action potential was followed by a marked depolarizing afterpotential (DAP). Rhythmic (4-10 Hz) bursts occurred during long-lasting depolarizing current pulses. 6. Small (3-10 mV), fast (1.5-4 ms), all-or-none depolarizing potentials were triggered by depolarizing current pulses. They are tentatively regarded as dendritic spikes recorded from the soma because their rate of occurrence changed as a function of the Vm and they were eventually blocked by hyperpolarization. 7. Synaptic stimulation of either thalamic or homotopic contralateral cortical areas elicited a sequence of excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs). Two components of the EPSP were revealed. At a hyperpolarized Vm, the initial component of the EPSP increased in amplitude, whereas the secondary component was blocked. Repetitive (10 Hz) stimulation of the thalamus or contralateral cortex elicited incremental responses. The augmentation phenomenon was due to an increase in the secondary component of the EPSP. The cortically elicited augmenting responses survived extensive thalamic lesions. A short IPSP and a long-lasting IPSP were evoked by thalamic or cortical stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

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