Computational model of carbachol-induced delta, theta, and gamma oscillations in the hippocampus

Paul H.E. Tiesinga; Jean-Marc Fellous; Jorge V. José; Terrence J. Sejnowski

doi:10.1002/hipo.1041

Gamma oscillations decompose the visual scene into object-based perceptual cycles: a computational model

Journal of Vision ◽

10.1167/10.7.1270 ◽

2010 ◽

Vol 10 (7) ◽

pp. 1270-1270

Author(s):

M. Thomas ◽

V. Rufin

Keyword(s):

Computational Model ◽

Gamma Oscillations ◽

Visual Scene ◽

Object Based

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Influence of NMDA and GABA synaptic dysfunction on the evoked gamma oscillations in a computational model of schizophrenia

Biologija ◽

10.6001/biologija.v63i2.3532 ◽

2017 ◽

Vol 63 (2) ◽

Author(s):

Rokas Jackevičius ◽

Bruce P. Graham ◽

Aušra Saudargienė

Keyword(s):

Neural Network ◽

Computational Modeling ◽

Computational Model ◽

Time Constant ◽

Gamma Oscillations ◽

Synaptic Dysfunction ◽

Spiking Neural Network ◽

Gamma Frequency ◽

Gated Channel ◽

Fast Spiking

Background. Schizophrenia is a psychiatric disorder which is characterized by delusions and hallucinations, and affects thoughts, behaviour and emotions. Major neuronal degeneration is not observed in schizophrenic patients, but abnormalities in cortical circuits are present. These abnormalities are reflected in impaired EEG gamma frequency (30–80 Hz), being crucial for many processes including sensation, perception, working memory, and attention. NMDA and GABA synaptic dysfunction is proposed as one of the possible mechanisms underlying the gamma oscillatory deficits in schizophrenia. Materials and Methods. We used a computational modeling approach to investigate the joint influence of NMDA and GABA synaptic dysfunction on gamma oscillations in cortex. We employed a computational model of a spiking neural network composed of 800 pyramidal neurons, 150 regular-spiking interneurons, and 50 fast-spiking interneurons. All cells were randomly interconnected. Network neurons received independent Poisson noise input at 4 Hz and 40 Hz drive excitatory stimulation. Fast-spiking interneuron GABA receptor-gated channel time constant was increased and NMDA receptor-gated channel synaptic conductance was decreased to represent synaptic dysfunction in schizophrenia. Results. Reducing NMDA conductance enhanced gamma power, and increasing decay time constant of GABA receptorgated channel attenuated gamma generation in a network. The effect of synaptic GABA alteration was more profound. Conclusions. NMDA and GABA synaptic dysfunction leads to the impaired gamma frequency oscillations in a spiking neural network of cortex. Computational modeling approach is a powerful tool to understand complex non-linear dynamical systems and intrinsic mechanisms of neuronal network activity in healthy and diseased brain.

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Kcns3 Deficiency Disrupts Parvalbumin Neuron Physiology in Mouse Prefrontal Cortex: Implications for the pathophysiology of schizophrenia

10.1101/2020.09.02.280107 ◽

2020 ◽

Author(s):

Takeaki Miyamae ◽

Takanori Hashimoto ◽

Monica Abraham ◽

Rika Kawabata ◽

Sho Koshikizawa ◽

...

Keyword(s):

Computational Model ◽

Cell Model ◽

Gamma Oscillations ◽

Spike Trains ◽

Repetitive Firing ◽

Mrna Levels ◽

Gene Encoding ◽

Gamma Frequency ◽

Channel Inactivation ◽

Deficient Mice

AbstractThe unique fast spiking (FS) phenotype of cortical parvalbumin-positive (PV) neurons depends on multiple subtypes of voltage-gated potassium channels (Kv). PV neurons selectively express Kcns3, the gene encoding Kv9.3 subunits, suggesting that Kcns3 expression is critical for the FS phenotype. KCNS3 expression is lower in PV neurons in schizophrenia, but the effects of this alteration are unclear, because Kv9.3 subunit function is poorly understood. We therefore assessed the role of Kv9.3 subunits in PV neuron function by combining gene expression analyses, computational modeling, and electrophysiology in acute slices from the cortex of Kcns3-deficient miceKcns3 mRNA levels were ~50% lower in cortical PV neurons from Kcns3-deficient relative to wildtype mice. While silent per se, Kv9.3 subunits are believed to amplify the Kv2.1 current in Kv2.1-Kv9.3 channel complexes. Hence, to assess the consequences of reducing Kv9.3 levels, we simulated the effects of decreasing the Kv2.1-mediated current in a computational model. The FS cell model with reduced Kv2.1 produced spike trains with irregular inter-spike intervals, or stuttering, and greater Na+ channel inactivation, possibly due to a smaller afterhyperpolarization. As in the computational model, PV basket cells (PVBCs) from Kcns3-deficient mice displayed spike trains with strong stuttering, which depressed PVBC firing, and smaller afterhyperpolarization. Moreover, Kcns3 deficiency impaired the recruitment of PVBCs by stimuli mimicking synaptic input during cortical UP states, which elicited bursts of spikes at gamma frequency. Our data suggest that Kv9.3 subunits are critical for PVBC physiology, and that KCNS3 deficiency in schizophrenia may impair the substrate of gamma oscillations.Significance statementIn the neocortex, Kcns3, the gene encoding voltage-dependent potassium (Kv) channel subunits Kv9.3, is selectively expressed by parvalbumin-positive (PV) neurons. Moreover, KCNS3 expression is decreased in PV neurons in schizophrenia. Kv 9.3 subunits are believed to amplify the current mediated by Kv2.1 subunits, however Kv9.3 function has not been investigated in PV cells.Here, simulations in a computational model and electrophysiological experiments with Kcns3-deficient mice revealed that Kcns3 deficiency disrupts repetitive firing in cortical PV neurons, possibly enhancing Na+ channel inactivation, and particularly with stimuli eliciting firing at gamma frequency band (30-80Hz). Our results suggest that Kv9.3 subunits are essential for PV neuron electrophysiology and that KCNS3 deficiency likely contributes to PV neuron dysfunction and gamma oscillation impairments in schizophrenia.

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