Personne :
Timofeev, Igor

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Timofeev
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Igor
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Université Laval. Département de psychiatrie et de neurosciences
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  • Publication
    Accès libre
    A wireless electro-optic platform for multimodal electrophysiology and optogenetics in freely moving rodents
    (Frontiers Media S.A., 2021-08-16) Bilodeau, Guillaume; Gagnon-Turcotte, Gabriel; L. Gagnon, Léonard; Keramidis, Iason; De Koninck, Yves; Ethier, Christian; Gosselin, Benoit; Timofeev, Igor
    This paper presents the design and the utilization of a wireless electro-optic platform to perform simultaneous multimodal electrophysiological recordings and optogenetic stimulation in freely moving rodents. The developed system can capture neural action potentials (AP), local field potentials (LFP) and electromyography (EMG) signals with up to 32 channels in parallel while providing four optical stimulation channels. The platform is using commercial off-the-shelf components (COTS) and a low-power digital field-programmable gate array (FPGA), to perform digital signal processing to digitally separate in real time the AP, LFP and EMG while performing signal detection and compression for mitigating wireless bandwidth and power consumption limitations. The different signal modalities collected on the 32 channels are time-multiplexed into a single data stream to decrease power consumption and optimize resource utilization. The data reduction strategy is based on signal processing and real-time data compression. Digital filtering, signal detection, and wavelet data compression are used inside the platform to separate the different electrophysiological signal modalities, namely the local field potentials (1–500 Hz), EMG (30–500 Hz), and the action potentials (300–5,000 Hz) and perform data reduction before transmitting the data. The platform achieves a measured data reduction ratio of 7.77 (for a firing rate of 50 AP/second) and weights 4.7 g with a 100-mAh battery, an on/off switch and a protective plastic enclosure. To validate the performance of the platform, we measured distinct electrophysiology signals and performed optogenetics stimulation in vivo in freely moving rondents. We recorded AP and LFP signals with the platform using a 16-microelectrode array implanted in the primary motor cortex of a Long Evans rat, both in anesthetized and freely moving conditions. EMG responses to optogenetic Channelrhodopsin-2 induced activation of motor cortex via optical fiber were also recorded in freely moving rodents.
  • Publication
    Accès libre
    Age dependency of trauma-induced neocortical epileptogenesis
    (Frontiers Research Foundation, 2013-09-18) Grand, Laszlo B.; Sejnowski, Terrence J.; Timofeev, Igor; Bazhenov, Maxim; Chauvette, Sylvain
    Trauma and brain infection are the primary sources of acquired epilepsy, which can occur at any age and may account for a high incidence of epilepsy in developing countries. We have explored the hypothesis that penetrating cortical wounds cause deafferentation of the neocortex, which triggers homeostatic plasticity and lead to epileptogenesis (Houweling et al., 2005). In partial deafferentation experiments of adult cats, acute seizures occurred in most preparations and chronic seizures occurred weeks to months after the operation in 65% of the animals (Nita et al., 2006, 2007; Nita and Timofeev, 2007). Similar deafferentation of young cats (age 8–12 months) led to some acute seizures, but we never observed chronic seizure activity even though there was enhanced slow-wave activity in the partially deafferented hemisphere during quiet wakefulness. This suggests that despite a major trauma, the homeostatic plasticity in young animals was able to restore normal levels of cortical excitability, but in fully adult cats the mechanisms underlying homeostatic plasticity may lead to an unstable cortical state. To test this hypothesis we made an undercut in the cortex of an elderly cat. After several weeks this animal developed seizure activity. These observations may lead to an intervention after brain trauma that prevents epileptogenesis from occurring in adults.
  • Publication
    Restreint
    Modulation of synaptic transmission in neocortex by network activities
    (European Neuroscience Association by Oxford University Press, 2005-03-09) Crochet, Sylvain; Timofeev, Igor; Boucetta, Soufiane; Chauvette, Sylvain
    Neocortical neurons integrate inputs from thousands of presynaptic neurons that fire in vivo with frequencies that can reach 20 Hz. An important issue in understanding cortical integration is to determine the actual impact of presynaptic firing on postsynaptic neuron in the context of an active network. We used dual intracellular recordings from synaptically connected neurons or microstimulation to study the properties of spontaneous and evoked single-axon excitatory postsynaptic potentials (EPSPs) in vivo, in barbiturate or ketamine−xylazine anaesthetized cats. We found that active states of the cortical network were associated with higher variability and decrease in amplitude and duration of the EPSPs owing to a shunting effect. Moreover, the number of apparent failures markedly increased during active states as compared with silent states. Single-axon EPSPs in vivo showed mainly paired-pulse facilitation, and the paired-pulse ratio increased during active states as compare to silent states, suggesting a decrease in release probability during active states. Raising extracellular Ca2+ concentration to 2.5–3.0 mm by reverse microdialysis reduced the number of apparent failures and significantly increased the mean amplitude of individual synaptic potentials. Quantitative analysis of spontaneous synaptic activity suggested that the proportion of presynaptic activity that impact at the soma of a cortical neuron in vivo was low because of a high failure rate, a shunting effect and probably dendritic filtering. We conclude that during active states of cortical network, the efficacy of synaptic transmission in individual synapses is low, thus safe transmission of information requires synchronized activity of a large population of presynaptic neurons.
  • Publication
    Restreint
    Detection of active and silent states in neocortical neurons from the field potential signal during slow-wave sleep
    (Oxford University Press, 2006-03-17) Mukovski, Mikhail; Timofeev, Igor; Chauvette, Sylvain; Volgushev, Maxim
    Oscillations of the local field potentials (LFPs) or electroencephalogram (EEG) at frequencies below 1 Hz are a hallmark of the slow-wave sleep. However, the timing of the underlying cellular events, which is an alternation of active and silent states of thalamocortical network, can be assessed only approximately from the phase of slow waves. Is it possible to detect, using the LFP or EEG, the timing of each episode of cellular activity or silence? With simultaneous recordings of the LFP and intracellular activity of 2–3 neocortical cells, we show that high–gamma-range (20–100 Hz) components in the LFP have significantly higher power when cortical cells are in active states as compared with silent-state periods. Exploiting this difference we have developed a new method, which uses the LFP signal to detect episodes of activity and silence of neocortical neurons. The method allows robust, reliable, and precise detection of timing of each episode of activity and silence of the neocortical network. It works with both surface and depth EEG, and its performance is affected little by the EEG prefiltering during recording. These results open new perspectives for studying differential operation of neural networks during periods of activity and silence, which rapidly alternate on the subsecond scale.
  • Publication
    Restreint
    In vivo models of cortical acquired epilepsy
    (Elsevier/North-Holland, 2015-09-03) Soltani, Sara; Timofeev, Igor; Chauvette, Sylvain; Seigneur, Josée
    The neocortex is the site of origin of several forms of acquired epilepsy. Here we provide a brief review of experimental models that were recently developed to study neocortical epileptogenesis as well as some major results obtained with these methods. Most of neocortical seizures appear to be nocturnal and it is known that neuronal activities reveal high levels of synchrony during slow-wave sleep. Therefore, we start the review with a description of mechanisms of neuronal synchronization and major forms of synchronized normal and pathological activities. Then, we describe three experimental models of seizures and epileptogenesis: ketamine–xylazine anesthesia as feline seizure triggered factor, cortical undercut as cortical penetrating wound model and neocortical kindling. Besides specific technical details describing these models we also provide major features of pathological brain activities recorded during epileptogenesis and seizures. The most common feature of all models of neocortical epileptogenesis is the increased duration of network silent states that up-regulates neuronal excitability and eventually leads to epilepsy.
  • Publication
    Accès libre
    Extracellular Ca2+ fluctuations in vivo affect afterhyperpolarization potential and modify firing patterns of neocortical neurons
    (Netherlands Elsevier, 2012-12-19) Crochet, Sylvain; Timofeev, Igor; Boucetta, Soufiane; Chauvette, Sylvain; Seigneur, Josée
    Neocortical neurons can be classified in four major electrophysiological types according to their pattern of discharge: regular-spiking (RS), intrinsically-bursting (IB), fast-rhythmic-bursting (FRB), and fast-spiking (FS). Previously, we have shown that these firing patterns are not fixed and can change as a function of membrane potential and states of vigilance. Other studies have reported that extracellular calcium concentration ([Ca2 +]o) fluctuates as a function of the phase of the cortical slow oscillation. In the present study we investigated how spontaneous and induced changes in [Ca2 +]o affect the properties of action potentials (APs) and firing patterns in cortical neurons in vivo. Intracellular recordings were performed in cats anesthetized with ketamine–xylazine during spontaneous [Ca2 +]o fluctuation and while changing [Ca2 +]o with reverse microdialysis. When [Ca2 +]o fluctuated spontaneously according to the phase of the slow oscillation, we found an increase of the firing threshold and a decrease of the afterhyperpolarization (AHP) amplitude during the depolarizing (active, up) phase of the slow oscillation and some neurons also changed their firing pattern as compared with the hyperpolarizing (silent, down) phase. Induced changes in [Ca2 +]o significantly affected the AP properties in all neurons. The AHP amplitude was increased in high calcium conditions and decreased in low calcium conditions, in particular the earliest components. Modulation of spike AHP resulted in notable modulation of intrinsic firing pattern and some RS neurons revealed burst firing when [Ca2 +]o was decreased. We also found an increase in AHP amplitude in high [Ca2 +]o with in vitro preparation. We suggest that during spontaneous network oscillations in vivo, the dynamic changes of firing patterns depend partially on fluctuations of the [Ca2 +]o.
  • Publication
    Restreint
    Long-range correlation of the membrane potential in neocortical neurons during slow oscillation
    (Elsevier, 2011-08-18) Volgushev, Maxim; Timofeev, Igor; Chauvette, Sylvain
    Large amplitude slow waves are characteristic for the summary brain activity, recorded as electroencephalogram (EEG) or local field potentials (LFP), during deep stages of sleep and some types of anesthesia. Slow rhythm of the synchronized EEG reflects an alternation of active (depolarized, UP) and silent (hyperpolarized, DOWN) states of neocortical neurons. In neurons, involvement in the generalized slow oscillation results in a long-range synchronization of changes of their membrane potential as well as their firing. Here, we aimed at intracellular analysis of details of this synchronization. We asked which components of neuronal activity exhibit long-range correlations during the synchronized EEG? To answer this question, we made simultaneous intracellular recordings from two to four neocortical neurons in cat neocortex. We studied how correlated is the occurrence of active and silent states, and how correlated are fluctuations of the membrane potential in pairs of neurons located close one to the other or separated by up to 13 mm. We show that strong long-range correlation of the membrane potential was observed only (i) during the slow oscillation but not during periods without the oscillation, (ii) during periods which included transitions between the states but not during within-the-state periods, and (iii) for the low-frequency (< 5 Hz) components of membrane potential fluctuations but not for the higher-frequency components (> 10 Hz). In contrast to the neurons located several millimeters one from the other, membrane potential fluctuations in neighboring neurons remain strongly correlated during periods without slow oscillation. We conclude that membrane potential correlation in distant neurons is brought about by synchronous transitions between the states, while activity within the states is largely uncorrelated. The lack of the generalized fine-scale synchronization of membrane potential changes in neurons during the active states of slow oscillation may allow individual neurons to selectively engage in short living episodes of correlated activity—a process that may be similar to dynamical formation of neuronal ensembles during activated brain states.
  • Publication
    Restreint
    Thalamocortical oscillations : local control of EEG slow waves.
    (Bentham Science Publishers, 2011-09-01) Timofeev, Igor; Chauvette, Sylvain
    This article starts with a brief review of the thalamocortical system architecture, which is composed of the projecting thalamic nuclei, the thalamic reticular nucleus, and the neocortex. Then we provide a description of the three states of vigilances followed by a detailed review of major brain rhythms present in the thalamocortical system, ranging from very slow to very fast oscillations. We provide descriptions of known mechanisms and hypotheses for unknown mechanisms for the generation of the different rhythms. The last part offers a detailed review on sleep slow oscillation describing its properties in the thalamocortical system, proposing a mechanism of generation of active states and a description of their propagation.
  • Publication
    Accès libre
    Sleep slow oscillation and plasticity
    (Current Biology, 2017-04-26) Timofeev, Igor; Chauvette, Sylvain
    It is well documented that sleep contributes to memory consolidation and it is also accepted that long-term synaptic plasticity plays a critical role in memory formation. The mechanisms of this sleep-dependent memory formation are unclear. Two main hypotheses are proposed. According to the first one, synapses are potentiated during wake; and during sleep they are scaled back to become available for the learning tasks in the next day. The other hypothesis is that sleep slow oscillations potentiate synapses that were depressed due to persistent activities during the previous day and that potentiation provides physiological basis for memory consolidation. The objective of this review is to group information on whether cortical synapses are up-scaled or down-scaled during sleep. We conclude that the majority of cortical synapses are up-regulated by sleep slow oscillation.
  • Publication
    Restreint
    Neocortical inhibitory activities and long-range afferents contribute to the synchronous onset of silent states of the neocortical slow oscillation
    (American Physiological Society, 2014-11-12) Lemieux, Maxime; Timofeev, Igor; Chauvette, Sylvain
    During slow-wave sleep, neurons of the thalamocortical network are engaged in a slow oscillation (<1 Hz), which consists of an alternation between the active and the silent states. Several studies have provided insights on the transition from the silent, which are essentially periods of disfacilitation, to the active states. However, the conditions leading to the synchronous onset of the silent state remain elusive. We hypothesized that a synchronous input to local inhibitory neurons could contribute to the transition to the silent state in the cat suprasylvian gyrus during natural sleep and under ketamine-xylazine anesthesia. After partial and complete deafferentation of the cortex, we found that the silent state onset was more variable among remote sites. We found that the transition to the silent state was preceded by a reduction in excitatory postsynaptic potentials and firing probability in cortical neurons. We tested the impact of chloride-mediated inhibition in the silent-state onset. We uncovered a long-duration (100–300 ms) inhibitory barrage occurring about 250 ms before the silent state onset in 3–6% of neurons during anesthesia and in 12–15% of cases during natural sleep. These inhibitory activities caused a decrease in cortical firing that reduced the excitatory drive in the neocortical network. That chain reaction of disfacilitation ends up on the silent state. Electrical stimuli could trigger a network silent state with a maximal efficacy in deep cortical layers. We conclude that long-range afferents to the neocortex and chloride-mediated inhibition play a role in the initiation of the silent state.