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.

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.

scholarly journals A Method to Estimate Synaptic Conductances From Membrane Potential Fluctuations

2004 ◽  
Vol 91 (6) ◽  
pp. 2884-2896 ◽  
Author(s):  
Michael Rudolph ◽  
Zuzanna Piwkowska ◽  
Mathilde Badoual ◽  
Thierry Bal ◽  
Alain Destexhe
Keyword(s):  
Membrane Potential ◽  
Computational Models ◽  
Network Activity ◽  
Intracellular Recordings ◽  
Neocortical Neurons ◽  
Underlying Network ◽  
Analytic Expression ◽  
Synaptic Conductances

In neocortical neurons, network activity can activate a large number of synaptic inputs, resulting in highly irregular subthreshold membrane potential ( Vm) fluctuations, commonly called “synaptic noise.” This activity contains information about the underlying network dynamics, but it is not easy to extract network properties from such complex and irregular activity. Here, we propose a method to estimate properties of network activity from intracellular recordings and test this method using theoretical and experimental approaches. The method is based on the analytic expression of the subthreshold Vm distribution at steady state in conductance-based models. Fitting this analytic expression to Vm distributions obtained from intracellular recordings provides estimates of the mean and variance of excitatory and inhibitory conductances. We test the accuracy of these estimates against computational models of increasing complexity. We also test the method using dynamic-clamp recordings of neocortical neurons in vitro. By using an on-line analysis procedure, we show that the measured conductances from spontaneous network activity can be used to re-create artificial states equivalent to real network activity. This approach should be applicable to intracellular recordings during different network states in vivo, providing a characterization of the global properties of synaptic conductances and possible insight into the underlying network mechanisms.

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.

Estimation of synaptic conductances and their variances from intracellular recordings of neocortical neurons in vivo

2004 ◽  
Vol 58-60 ◽  
pp. 387-392 ◽  
Author(s):  
Michael Rudolph ◽  
J. Guillaume Pelletier ◽  
Denis Paré ◽  
Alain Destexhe
Keyword(s):  
Intracellular Recordings ◽  
Neocortical Neurons ◽  
Synaptic Conductances

Properties of Action-Potential Initiation in Neocortical Pyramidal Cells: Evidence From Whole Cell Axon Recordings

2007 ◽  
Vol 97 (1) ◽  
pp. 746-760 ◽  
Author(s):  
Yousheng Shu ◽  
Alvaro Duque ◽  
Yuguo Yu ◽  
Bilal Haider ◽  
David A. McCormick
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Initial Segment ◽  
Pyramidal Cells ◽  
Synaptic Activity ◽  
Up States ◽  
Action Potential Initiation ◽  
Potential Initiation

Cortical pyramidal cells are constantly bombarded by synaptic activity, much of which arises from other cortical neurons, both in normal conditions and during epileptic seizures. The action potentials generated by barrages of synaptic activity may exhibit a variable site of origin. Here we performed simultaneous whole cell recordings from the soma and axon or soma and apical dendrite of layer 5 pyramidal neurons during normal recurrent network activity (up states), the intrasomatic or intradendritic injection of artificial synaptic barrages, and during epileptiform discharges in vitro. We demonstrate that under all of these conditions, the real or artificial synaptic bombardments propagate through the dendrosomatic-axonal arbor and consistently initiate action potentials in the axon initial segment that then propagate to other parts of the cell. Action potentials recorded intracellularly in vivo during up states and in response to visual stimulation exhibit properties indicating that they are typically initiated in the axon. Intracortical axons were particularly well suited to faithfully follow the generation of action potentials by the axon initial segment. Action-potential generation was more reliable in the distal axon than at the soma during epileptiform activity. These results indicate that the axon is the preferred site of action-potential initiation in cortical pyramidal cells, both in vivo and in vitro, with state-dependent back propagation through the somatic and dendritic compartments.

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.

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.

The high-conductance state of neocortical neurons in vivo

2003 ◽  
Vol 4 (9) ◽  
pp. 739-751 ◽  
Author(s):  
Alain Destexhe ◽  
Michael Rudolph ◽  
Denis Paré
Keyword(s):  
Neocortical Neurons ◽  
High Conductance State ◽  
Conductance State ◽  
High Conductance

Synaptic and intrinsic control of membrane excitability of neostriatal neurons. I. An in vivo analysis

1990 ◽  
Vol 63 (4) ◽  
pp. 651-662 ◽  
Author(s):  
P. Calabresi ◽  
N. B. Mercuri ◽  
A. Stefani ◽  
G. Bernardi
Keyword(s):  
Substantia Nigra ◽  
Firing Rate ◽  
Action Potentials ◽  
Input Resistance ◽  
Membrane Properties ◽  
Strong Increase ◽  
Synaptic Potential ◽  
Membrane Excitability ◽  
Stimulation Of

1. The relationship between membrane properties of neostriatal neurons and spontaneous and evoked synaptic potentials was studied with the use of intracellular recordings from anesthetized rats. Most of these neurons showed regular or irregular spontaneous depolarizing potentials that only in a few cases triggered action potentials at resting level. 2. The stimulation of the ipsilateral substantia nigra or of the sensorimotor cortex produced a relatively fast depolarizing post-synaptic potential (EPSP). In some cells this potential was followed by an inhibitory period that appeared as an hyperpolarization when the cell was depolarized from the resting level (inhibitory postsynaptic potential, IPSP). A late and long-lasting depolarization (LD) followed the EPSP or the EPSP-IPSP sequence. 3. Repetitive discharge with little adaptation was observed during direct depolarization. Most of the neurons tested for current-voltage (I-V) relationship showed nonlinearity of the input resistance in the hyperpolarizing direction. Spontaneous and evoked EPSPs were decreased in their amplitude and duration when the membrane potential was held at levels more hyperpolarized than -85 mV because of the strong rectification at these levels of hyperpolarization. 4. Local microiontophoretic application of bicuculline (BIC) or systemic administration of BIC and pentylenetetrazole (PTZ) produced a reduction of the IPSPs. The reduction of the inhibitory transmission caused a strong increase of the LD. The current-evoked firing pattern was not greatly altered. 5. The intracellular application of cesium increased the amplitude and the duration of the spontaneous depolarizations that triggered bursts of action potentials under this condition. Spikes were broadened and the rectification in the hyperpolarization direction was reduced. 6. Iontophoretically applied cadmium strongly depressed the amplitude of the spontaneous and evoked postsynaptic potentials. During cadmium application, nigral stimulation produced constant latency, all-or-none spikes in the absence of any synaptic potential. 7. Repetitive stimulation of the ipsilateral substantia nigra by electrical shocks (5 Hz, 25 s) produced a progressive and reversible decrease of the spontaneous depolarizing potentials (SDPs) and a decrease of the firing rate. In the same cells, when the train of stimulation was delivered in the ipsilateral cortex, a membrane depolarization coupled with an increase of the firing rate was observed. 8. We conclude that although synaptic circuits mediate a phasic inhibition in neostriatum, the low level of spontaneous firing of most neostriatal neurons is mainly because of the effects that membrane properties exert on the spontaneous and the evoked synaptic depolarizations in the striatum.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

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