Maxim Bazhenov - Academia.edu (original) (raw)

Papers by Maxim Bazhenov

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2011

Epileptic seizures are characterized by periods of recurrent, highly synchronized activity that s... more Epileptic seizures are characterized by periods of recurrent, highly synchronized activity that spontaneously terminates, followed by postictal state when neuronal activity is generally depressed. The mechanisms for spontaneous seizure termination and postictal depression remain poorly understood. Using a realistic computational model, we demonstrate that termination of seizure and postictal depression state may be mediated by dynamics of the intracellular and extracellular ion concentrations. Spontaneous termination was linked to progressive increase of intracellular sodium concentration mediated by activation of sodium channels during highly active epileptic state. In contrast, an increase of intracellular chloride concentration extended seizure duration making possible long-lasting epileptic activity characterized by multiple transitions between tonic and clonic states. After seizure termination, the extracellular potassium was reduced below baseline, resulting in postictal depre...

Extracellular ion concentrations change as a function of neuronal activity and also represent imp... more Extracellular ion concentrations change as a function of neuronal activity and also represent important factors influencing the dynamic state of a population of neurons. In particular, relatively small changes in extracellular potassium concentration (� K+� o) mediate substantial changes in neuronal excitability and intrinsic firing patterns. While experimental approaches are limited in their abil- ity to shed light on the

BMC Neuroscience, 2014

Sleep is critical for regulation of synaptic efficacy, consolidation of memories and learning. It... more Sleep is critical for regulation of synaptic efficacy, consolidation of memories and learning. It has been proposed that synaptic plasticity associated with sleep rhythms could contribute to consolidation of memories acquired during wakefulness. It was suggested that in the active state of sleep slow wave oscillation, the hippocampal formation activates latent memories stored in the neocortex (replay) and induce permanent changes in synaptic conductances.

BMC Neuroscience, 2014

Sleep is known to be important for memory consolidation , and memories are thought to be stored i... more Sleep is known to be important for memory consolidation , and memories are thought to be stored in the hippocampus during the wakefulness and "transferred" to cortex during sleep . Recently, memory replayrepeatable sequences of pyramidal cell firinghas been demonstrated during sleep, and associated with characteristic brain oscillations, giving rise to the hypothesis that these may form the critical neural substrate of memory consolidation. Tampering with replay can disrupt memory formation and consolidation , and the mechanisms underlying sequence replay are still unknown.

Jasper's Basic Mechanisms of the Epilepsies, 2012

Neuronal synchronization can be defined as a correlated appearance in time of two or more events ... more Neuronal synchronization can be defined as a correlated appearance in time of two or more events associated with various aspects of neuronal activity. Neuronal synchronization depends on chemical and electrical synaptic as well as ephaptic and non-specific interactions. We consider two distinct types of neuronal synchronization: local synchronization that is responsible for the generation of local field potentials; and long-range synchronization, detected with distantly located electrodes and mediated primarily via chemical synaptic interactions, which contributes to the EEG synchronization. Neocortical synchronization during sleep and wakefulness is often associated with rhythmic oscillations of neuronal activity: slow oscillation, delta, spindle, beta, gamma and ripples. Normal thalamocortical oscillations [sleep or wake oscillations] are generated as a result of both local and long-range synchronization. During paroxysmal [seizure] activity, the role of chemical synaptic interactions decreases because of alterations in ionic composition that impairs synaptic transmission. Synchronized activities in large population of neurons (such as neocortex) may occur as nearly simultaneous patterns across an entire population or as propagating waves. Neocortical synchronization is controlled by the activities in ascending systems: cholinergic, norepinephrinergic and serotoninergic. The presence of cortico-thalamo-cortical feedback loops contribute to the synchronization of cortical activities. We propose that all the types of neuronal interactions contribute to the generation of synchronous oscillatory activities, but the ratio of their contribution is different for different types of oscillations.

Nature neuroscience, 2007

In the mushroom body of insects, odors are represented by very few spikes in a small number of ne... more In the mushroom body of insects, odors are represented by very few spikes in a small number of neurons, a highly efficient strategy known as sparse coding. Physiological studies of these neurons have shown that sparseness is maintained across thousand-fold changes in odor concentration. Using a realistic computational model, we propose that sparseness in the olfactory system is regulated by adaptive feedforward inhibition. When odor concentration changes, feedforward inhibition modulates the duration of the temporal window over which the mushroom body neurons may integrate excitatory presynaptic input. This simple adaptive mechanism could maintain the sparseness of sensory representations across wide ranges of stimulus conditions.

Journal of neurophysiology, Jan 14, 2015

Ionic concentrations fluctuate significantly during epileptic seizures. In this study, we demonst... more Ionic concentrations fluctuate significantly during epileptic seizures. In this study, we demonstrate that changes in the K(+) and Na(+) intra- and extracellular ion concentrations during seizure affect the neuron membrane potential by modulating the outward Na(+)/K(+) pump current. First, we show that increase of the outward Na(+)/K(+) pump current mediates termination of seizures when there is a progressive increase in the intracellular Na(+) concentration. Second, we show that the Na(+)/K(+) pump current is crucial in maintaining the stability of the physiological network state; a reduction of this current leads to the onset of seizures via a positive feedback loop. We then present a novel dynamical mechanism for bursting in neurons with a reduced Na(+)/K(+) pump. Overall, our study demonstrates the profound role of the current mediated by Na(+)/K(+) on the stability of neuronal dynamics that was previously unknown.

PloS one, 2014

Reward-modulated spike timing dependent plasticity (STDP) combines unsupervised STDP with a reinf... more Reward-modulated spike timing dependent plasticity (STDP) combines unsupervised STDP with a reinforcement signal that modulates synaptic changes. It was proposed as a learning rule capable of solving the distal reward problem in reinforcement learning. Nonetheless, performance and limitations of this learning mechanism have yet to be tested for its ability to solve biological problems. In our work, rewarded STDP was implemented to model foraging behavior in a simulated environment. Over the course of training the network of spiking neurons developed the capability of producing highly successful decision-making. The network performance remained stable even after significant perturbations of synaptic structure. Rewarded STDP alone was insufficient to learn effective decision making due to the difficulty maintaining homeostatic equilibrium of synaptic weights and the development of local performance maxima. Our study predicts that successful learning requires stabilizing mechanisms tha...

Frontiers in neuroengineering, 2012

In a variety of neuronal systems it has been hypothesized that inhibitory interneurons corral pri... more In a variety of neuronal systems it has been hypothesized that inhibitory interneurons corral principal neurons into synchronously firing groups that encode sensory information and sub-serve behavior (Buzsáki and Chrobak, 1995; Buzsáki, 2008). This mechanism is particularly relevant to the olfactory system where spatiotemporal patterns of projection neuron (PN) activity act as robust markers of odor attributes (Laurent et al., 1996; Wehr and Laurent, 1996). In the insect antennal lobe (AL), a network of local inhibitory interneurons arborizes extensively throughout the AL (Leitch and Laurent, 1996) providing inhibitory input to the cholinergic PNs. Our theoretical work has attempted to elaborate the exact role of inhibition in the generation of odor specific PN responses (Bazhenov et al., 2001a,b; Assisi et al., 2011). In large-scale AL network models we characterized the inhibitory sub-network by its coloring (Assisi et al., 2011) and showed that it can entrain excitatory PNs to th...

Neuron, Jan 12, 2010

The remarkable performance of the olfactory system in classifying and categorizing the complex ol... more The remarkable performance of the olfactory system in classifying and categorizing the complex olfactory environment is built upon several basic neural circuit motifs. These include forms of inhibition that may play comparable roles in widely divergent species. In this issue of Neuron, a new study by Stokes and Isaacson sheds light on how elementary types of inhibition dynamically interact.

Physical review. E, Statistical, nonlinear, and soft matter physics, 2005

We study the reliability of cortical neuron responses to periodically modulated synaptic stimuli.... more We study the reliability of cortical neuron responses to periodically modulated synaptic stimuli. Simple map-based models of two different types of cortical neurons are constructed to replicate the intrinsic resonances of reliability found in experimental data and to explore the effects of those resonance properties on collective behavior in a cortical network model containing excitatory and inhibitory cells. We show that network interactions can enhance the frequency range of reliable responses and that the latter can be controlled by the strength of synaptic connections. The underlying dynamical mechanisms of reliability enhancement are discussed.

Neuron, Jan 5, 2005

Recordings in the locust antennal lobe (AL) reveal activity-dependent, stimulus-specific changes ... more Recordings in the locust antennal lobe (AL) reveal activity-dependent, stimulus-specific changes in projection neuron (PN) and local neuron response patterns over repeated odor trials. During the first few trials, PN response intensity decreases, while spike time precision increases, and coherent oscillations, absent at first, quickly emerge. We examined this "fast odor learning" with a realistic computational model of the AL. Activity-dependent facilitation of AL inhibitory synapses was sufficient to simulate physiological recordings of fast learning. In addition, in experiments with noisy inputs, a network including synaptic facilitation of both inhibition and excitation responded with reliable spatiotemporal patterns from trial to trial despite the noise. A network lacking fast plasticity, however, responded with patterns that varied across trials, reflecting the input variability. Thus, our study suggests that fast olfactory learning results from stimulus-specific, act...

Thalamus & related systems, 2005

Mechanisms underlying seizure cessation remain elusive. The Lennox-Gastaut syndrome, a severe chi... more Mechanisms underlying seizure cessation remain elusive. The Lennox-Gastaut syndrome, a severe childhood epileptic disorder, is characterized by episodes of seizure with alternating epochs of spike-wave and fast run discharges. In a detailed computational model that incorporates extracellular potassium dynamics, we studied the dynamics of these state transitions between slow and fast oscillations. We show that dynamic modulation of synaptic transmission can cause termination of paroxysmal activity. An activity-dependent shift in the balance between synaptic excitation and inhibition towards more excitation caused seizure termination by favoring the slow oscillatory state, which permits recovery of baseline extracellular potassium concentration. We found that slow synaptic depression and change in chloride reversal potential can have similar effects on the seizure dynamics. Our results indicate a novel role for synaptic dynamics during epileptic neural activity patterns.

Drug discovery today. Disease models, 2008

Epileptic seizures constitute a complex multiscale phenomenon that is characterized by synchroniz... more Epileptic seizures constitute a complex multiscale phenomenon that is characterized by synchronized hyperexcitation of neurons in neuronal networks. Recent progress in understanding pathological seizure dynamics provides crucial insights into underlying mechanisms and possible new avenues for the development of novel treatment modalities. Here we review some recent work that combines in vivo experiments and computational modeling to unravel the pathophysiology of seizures of cortical origin. We particularly focus on how activity-dependent changes in extracellular potassium concentration affects the intrinsic dynamics of neurons involved in cortical seizures characterized by spike/wave complexes and fast runs.

Computational Neuroscience in Epilepsy, 2008

Extracellular ion concentrations change as a function of neuronal activity and also represent imp... more Extracellular ion concentrations change as a function of neuronal activity and also represent important factors influencing the dynamic state of a population of neurons. In particular, relatively small changes in extracellular potassium concentration ( K + o ) mediate substantial changes in neuronal excitability and intrinsic firing patterns. While experimental approaches are limited in their ability to shed light on the dynamic feedback interaction between ion concentration and neural activity, computational models and dynamic system theory provide powerful tools to study activity-dependent modulation of intrinsic excitability mediated by extracellular ion concentration dynamics. In this chapter, we discuss the potential role of extracellular potassium concentration dynamics in the generation of epileptiform activity in neocortical networks. Detailed bifurcation analysis of a model pyramidal cell revealed a bistability with hysteresis between two distinct firing modes (tonic firing and slow bursting) for mildly elevated K + o . In neocortical network models, this bistability gives rise to previously unexplained slow alternating epochs of fast runs and slow bursting as recorded in vivo during neocortical electrographic seizures in cats and in human patients with the Lennox-Gastaut syndrome. We conclude that extracellular potassium concentration dynamics may play an important role in the generation of seizures.

Frontiers in cellular neuroscience, 2013

Trauma and brain infection are the primary sources of acquired epilepsy, which can occur at any a... more 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 etal., 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 etal., 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 excitabil...

PLoS computational biology, 2014

Perceptual learning has been used to probe the mechanisms of cortical plasticity in the adult bra... more Perceptual learning has been used to probe the mechanisms of cortical plasticity in the adult brain. Feedback projections are ubiquitous in the cortex, but little is known about their role in cortical plasticity. Here we explore the hypothesis that learning visual orientation discrimination involves learning-dependent plasticity of top-down feedback inputs from higher cortical areas, serving a different function from plasticity due to changes in recurrent connections within a cortical area. In a Hodgkin-Huxley-based spiking neural network model of visual cortex, we show that modulation of feedback inputs to V1 from higher cortical areas results in shunting inhibition in V1 neurons, which changes the response properties of V1 neurons. The orientation selectivity of V1 neurons is enhanced without changing orientation preference, preserving the topographic organizations in V1. These results provide new insights to the mechanisms of plasticity in the adult brain, reconciling apparently ...

Proceedings of the National Academy of Sciences of the United States of America, Jan 24, 2015

Precisely timed action potentials related to stimuli and behavior have been observed in the cereb... more Precisely timed action potentials related to stimuli and behavior have been observed in the cerebral cortex. However, information carried by the precise spike timing has to propagate through many cortical areas, and noise could disrupt millisecond precision during the transmission. Previous studies have demonstrated that only strong stimuli that evoke a large number of spikes with small dispersion of spike times can propagate through multilayer networks without degrading the temporal precision. Here we show that feedback projections can increase the number of spikes in spike volleys without degrading their temporal precision. Feedback also increased the range of spike volleys that can propagate through multilayer networks. Our work suggests that feedback projections could be responsible for the reliable propagation of information encoded in spike times through cortex, and thus could serve as an attentional mechanism to regulate the flow of information in the cortex. Feedback project...

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2011

Epileptic seizures are characterized by periods of recurrent, highly synchronized activity that s... more Epileptic seizures are characterized by periods of recurrent, highly synchronized activity that spontaneously terminates, followed by postictal state when neuronal activity is generally depressed. The mechanisms for spontaneous seizure termination and postictal depression remain poorly understood. Using a realistic computational model, we demonstrate that termination of seizure and postictal depression state may be mediated by dynamics of the intracellular and extracellular ion concentrations. Spontaneous termination was linked to progressive increase of intracellular sodium concentration mediated by activation of sodium channels during highly active epileptic state. In contrast, an increase of intracellular chloride concentration extended seizure duration making possible long-lasting epileptic activity characterized by multiple transitions between tonic and clonic states. After seizure termination, the extracellular potassium was reduced below baseline, resulting in postictal depre...

Extracellular ion concentrations change as a function of neuronal activity and also represent imp... more Extracellular ion concentrations change as a function of neuronal activity and also represent important factors influencing the dynamic state of a population of neurons. In particular, relatively small changes in extracellular potassium concentration (� K+� o) mediate substantial changes in neuronal excitability and intrinsic firing patterns. While experimental approaches are limited in their abil- ity to shed light on the

BMC Neuroscience, 2014

Sleep is critical for regulation of synaptic efficacy, consolidation of memories and learning. It... more Sleep is critical for regulation of synaptic efficacy, consolidation of memories and learning. It has been proposed that synaptic plasticity associated with sleep rhythms could contribute to consolidation of memories acquired during wakefulness. It was suggested that in the active state of sleep slow wave oscillation, the hippocampal formation activates latent memories stored in the neocortex (replay) and induce permanent changes in synaptic conductances.

BMC Neuroscience, 2014

Sleep is known to be important for memory consolidation , and memories are thought to be stored i... more Sleep is known to be important for memory consolidation , and memories are thought to be stored in the hippocampus during the wakefulness and "transferred" to cortex during sleep . Recently, memory replayrepeatable sequences of pyramidal cell firinghas been demonstrated during sleep, and associated with characteristic brain oscillations, giving rise to the hypothesis that these may form the critical neural substrate of memory consolidation. Tampering with replay can disrupt memory formation and consolidation , and the mechanisms underlying sequence replay are still unknown.

Jasper's Basic Mechanisms of the Epilepsies, 2012

Neuronal synchronization can be defined as a correlated appearance in time of two or more events ... more Neuronal synchronization can be defined as a correlated appearance in time of two or more events associated with various aspects of neuronal activity. Neuronal synchronization depends on chemical and electrical synaptic as well as ephaptic and non-specific interactions. We consider two distinct types of neuronal synchronization: local synchronization that is responsible for the generation of local field potentials; and long-range synchronization, detected with distantly located electrodes and mediated primarily via chemical synaptic interactions, which contributes to the EEG synchronization. Neocortical synchronization during sleep and wakefulness is often associated with rhythmic oscillations of neuronal activity: slow oscillation, delta, spindle, beta, gamma and ripples. Normal thalamocortical oscillations [sleep or wake oscillations] are generated as a result of both local and long-range synchronization. During paroxysmal [seizure] activity, the role of chemical synaptic interactions decreases because of alterations in ionic composition that impairs synaptic transmission. Synchronized activities in large population of neurons (such as neocortex) may occur as nearly simultaneous patterns across an entire population or as propagating waves. Neocortical synchronization is controlled by the activities in ascending systems: cholinergic, norepinephrinergic and serotoninergic. The presence of cortico-thalamo-cortical feedback loops contribute to the synchronization of cortical activities. We propose that all the types of neuronal interactions contribute to the generation of synchronous oscillatory activities, but the ratio of their contribution is different for different types of oscillations.

Nature neuroscience, 2007

In the mushroom body of insects, odors are represented by very few spikes in a small number of ne... more In the mushroom body of insects, odors are represented by very few spikes in a small number of neurons, a highly efficient strategy known as sparse coding. Physiological studies of these neurons have shown that sparseness is maintained across thousand-fold changes in odor concentration. Using a realistic computational model, we propose that sparseness in the olfactory system is regulated by adaptive feedforward inhibition. When odor concentration changes, feedforward inhibition modulates the duration of the temporal window over which the mushroom body neurons may integrate excitatory presynaptic input. This simple adaptive mechanism could maintain the sparseness of sensory representations across wide ranges of stimulus conditions.

Journal of neurophysiology, Jan 14, 2015

Ionic concentrations fluctuate significantly during epileptic seizures. In this study, we demonst... more Ionic concentrations fluctuate significantly during epileptic seizures. In this study, we demonstrate that changes in the K(+) and Na(+) intra- and extracellular ion concentrations during seizure affect the neuron membrane potential by modulating the outward Na(+)/K(+) pump current. First, we show that increase of the outward Na(+)/K(+) pump current mediates termination of seizures when there is a progressive increase in the intracellular Na(+) concentration. Second, we show that the Na(+)/K(+) pump current is crucial in maintaining the stability of the physiological network state; a reduction of this current leads to the onset of seizures via a positive feedback loop. We then present a novel dynamical mechanism for bursting in neurons with a reduced Na(+)/K(+) pump. Overall, our study demonstrates the profound role of the current mediated by Na(+)/K(+) on the stability of neuronal dynamics that was previously unknown.

PloS one, 2014

Reward-modulated spike timing dependent plasticity (STDP) combines unsupervised STDP with a reinf... more Reward-modulated spike timing dependent plasticity (STDP) combines unsupervised STDP with a reinforcement signal that modulates synaptic changes. It was proposed as a learning rule capable of solving the distal reward problem in reinforcement learning. Nonetheless, performance and limitations of this learning mechanism have yet to be tested for its ability to solve biological problems. In our work, rewarded STDP was implemented to model foraging behavior in a simulated environment. Over the course of training the network of spiking neurons developed the capability of producing highly successful decision-making. The network performance remained stable even after significant perturbations of synaptic structure. Rewarded STDP alone was insufficient to learn effective decision making due to the difficulty maintaining homeostatic equilibrium of synaptic weights and the development of local performance maxima. Our study predicts that successful learning requires stabilizing mechanisms tha...

Frontiers in neuroengineering, 2012

In a variety of neuronal systems it has been hypothesized that inhibitory interneurons corral pri... more In a variety of neuronal systems it has been hypothesized that inhibitory interneurons corral principal neurons into synchronously firing groups that encode sensory information and sub-serve behavior (Buzsáki and Chrobak, 1995; Buzsáki, 2008). This mechanism is particularly relevant to the olfactory system where spatiotemporal patterns of projection neuron (PN) activity act as robust markers of odor attributes (Laurent et al., 1996; Wehr and Laurent, 1996). In the insect antennal lobe (AL), a network of local inhibitory interneurons arborizes extensively throughout the AL (Leitch and Laurent, 1996) providing inhibitory input to the cholinergic PNs. Our theoretical work has attempted to elaborate the exact role of inhibition in the generation of odor specific PN responses (Bazhenov et al., 2001a,b; Assisi et al., 2011). In large-scale AL network models we characterized the inhibitory sub-network by its coloring (Assisi et al., 2011) and showed that it can entrain excitatory PNs to th...

Neuron, Jan 12, 2010

The remarkable performance of the olfactory system in classifying and categorizing the complex ol... more The remarkable performance of the olfactory system in classifying and categorizing the complex olfactory environment is built upon several basic neural circuit motifs. These include forms of inhibition that may play comparable roles in widely divergent species. In this issue of Neuron, a new study by Stokes and Isaacson sheds light on how elementary types of inhibition dynamically interact.

Physical review. E, Statistical, nonlinear, and soft matter physics, 2005

We study the reliability of cortical neuron responses to periodically modulated synaptic stimuli.... more We study the reliability of cortical neuron responses to periodically modulated synaptic stimuli. Simple map-based models of two different types of cortical neurons are constructed to replicate the intrinsic resonances of reliability found in experimental data and to explore the effects of those resonance properties on collective behavior in a cortical network model containing excitatory and inhibitory cells. We show that network interactions can enhance the frequency range of reliable responses and that the latter can be controlled by the strength of synaptic connections. The underlying dynamical mechanisms of reliability enhancement are discussed.

Neuron, Jan 5, 2005

Recordings in the locust antennal lobe (AL) reveal activity-dependent, stimulus-specific changes ... more Recordings in the locust antennal lobe (AL) reveal activity-dependent, stimulus-specific changes in projection neuron (PN) and local neuron response patterns over repeated odor trials. During the first few trials, PN response intensity decreases, while spike time precision increases, and coherent oscillations, absent at first, quickly emerge. We examined this "fast odor learning" with a realistic computational model of the AL. Activity-dependent facilitation of AL inhibitory synapses was sufficient to simulate physiological recordings of fast learning. In addition, in experiments with noisy inputs, a network including synaptic facilitation of both inhibition and excitation responded with reliable spatiotemporal patterns from trial to trial despite the noise. A network lacking fast plasticity, however, responded with patterns that varied across trials, reflecting the input variability. Thus, our study suggests that fast olfactory learning results from stimulus-specific, act...

Thalamus & related systems, 2005

Mechanisms underlying seizure cessation remain elusive. The Lennox-Gastaut syndrome, a severe chi... more Mechanisms underlying seizure cessation remain elusive. The Lennox-Gastaut syndrome, a severe childhood epileptic disorder, is characterized by episodes of seizure with alternating epochs of spike-wave and fast run discharges. In a detailed computational model that incorporates extracellular potassium dynamics, we studied the dynamics of these state transitions between slow and fast oscillations. We show that dynamic modulation of synaptic transmission can cause termination of paroxysmal activity. An activity-dependent shift in the balance between synaptic excitation and inhibition towards more excitation caused seizure termination by favoring the slow oscillatory state, which permits recovery of baseline extracellular potassium concentration. We found that slow synaptic depression and change in chloride reversal potential can have similar effects on the seizure dynamics. Our results indicate a novel role for synaptic dynamics during epileptic neural activity patterns.

Drug discovery today. Disease models, 2008

Epileptic seizures constitute a complex multiscale phenomenon that is characterized by synchroniz... more Epileptic seizures constitute a complex multiscale phenomenon that is characterized by synchronized hyperexcitation of neurons in neuronal networks. Recent progress in understanding pathological seizure dynamics provides crucial insights into underlying mechanisms and possible new avenues for the development of novel treatment modalities. Here we review some recent work that combines in vivo experiments and computational modeling to unravel the pathophysiology of seizures of cortical origin. We particularly focus on how activity-dependent changes in extracellular potassium concentration affects the intrinsic dynamics of neurons involved in cortical seizures characterized by spike/wave complexes and fast runs.

Computational Neuroscience in Epilepsy, 2008

Extracellular ion concentrations change as a function of neuronal activity and also represent imp... more Extracellular ion concentrations change as a function of neuronal activity and also represent important factors influencing the dynamic state of a population of neurons. In particular, relatively small changes in extracellular potassium concentration ( K + o ) mediate substantial changes in neuronal excitability and intrinsic firing patterns. While experimental approaches are limited in their ability to shed light on the dynamic feedback interaction between ion concentration and neural activity, computational models and dynamic system theory provide powerful tools to study activity-dependent modulation of intrinsic excitability mediated by extracellular ion concentration dynamics. In this chapter, we discuss the potential role of extracellular potassium concentration dynamics in the generation of epileptiform activity in neocortical networks. Detailed bifurcation analysis of a model pyramidal cell revealed a bistability with hysteresis between two distinct firing modes (tonic firing and slow bursting) for mildly elevated K + o . In neocortical network models, this bistability gives rise to previously unexplained slow alternating epochs of fast runs and slow bursting as recorded in vivo during neocortical electrographic seizures in cats and in human patients with the Lennox-Gastaut syndrome. We conclude that extracellular potassium concentration dynamics may play an important role in the generation of seizures.

Frontiers in cellular neuroscience, 2013

Trauma and brain infection are the primary sources of acquired epilepsy, which can occur at any a... more 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 etal., 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 etal., 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 excitabil...

PLoS computational biology, 2014

Perceptual learning has been used to probe the mechanisms of cortical plasticity in the adult bra... more Perceptual learning has been used to probe the mechanisms of cortical plasticity in the adult brain. Feedback projections are ubiquitous in the cortex, but little is known about their role in cortical plasticity. Here we explore the hypothesis that learning visual orientation discrimination involves learning-dependent plasticity of top-down feedback inputs from higher cortical areas, serving a different function from plasticity due to changes in recurrent connections within a cortical area. In a Hodgkin-Huxley-based spiking neural network model of visual cortex, we show that modulation of feedback inputs to V1 from higher cortical areas results in shunting inhibition in V1 neurons, which changes the response properties of V1 neurons. The orientation selectivity of V1 neurons is enhanced without changing orientation preference, preserving the topographic organizations in V1. These results provide new insights to the mechanisms of plasticity in the adult brain, reconciling apparently ...

Proceedings of the National Academy of Sciences of the United States of America, Jan 24, 2015

Precisely timed action potentials related to stimuli and behavior have been observed in the cereb... more Precisely timed action potentials related to stimuli and behavior have been observed in the cerebral cortex. However, information carried by the precise spike timing has to propagate through many cortical areas, and noise could disrupt millisecond precision during the transmission. Previous studies have demonstrated that only strong stimuli that evoke a large number of spikes with small dispersion of spike times can propagate through multilayer networks without degrading the temporal precision. Here we show that feedback projections can increase the number of spikes in spike volleys without degrading their temporal precision. Feedback also increased the range of spike volleys that can propagate through multilayer networks. Our work suggests that feedback projections could be responsible for the reliable propagation of information encoded in spike times through cortex, and thus could serve as an attentional mechanism to regulate the flow of information in the cortex. Feedback project...