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Ali Mahdavi: Neurophysiological and theoretical study of cellular and synaptic mechanisms underlying aberrant thalamocortical oscillations in a rodent model of psychotic transition

Inserm U1114, University of Strasbourg AND Bernstein Center Freiburg, University of Freiburg [PhD Seminar]
When Dec 08, 2020
from 05:15 PM to 05:45 PM
Where Zoom Meeting. Meeting ID and password will be sent with e-mail invitation. You can also ask Fiona Siegfried for Meeting ID and password.
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Abstract

BACKGROUND: In patients with psychotic disorders, sleep spindles (9-16 Hz) are reduced, supporting the hypothesis that the thalamus and glutamate receptors play a crucial etio- pathophysiological role, whose underlying mechanisms remain unknown. We hypothesized that a reduced function of NMDA receptors is involved in the spindle deficit observed in schizophrenia.

METHODS: In the experimental part, an electrophysiological multisite cell-to-network exploration was used to investigate, in pentobarbital-sedated rats, the effects of a single psychotomimetic dose of the NMDA glutamate receptor antagonist ketamine in the sensorimotor thalamocortical (TC) systems. In the computational part, the spiking network model of the 3-stage CT-TRN-TC loop circuit was simulated using NEST in order to elucidate the functional interactions between different components of the somatosensory CT-TRN-TC system under physiological and pathological conditions, especially by systematically changing the parameters of the NMDA receptors including the connection probability, peak conductance, rise and decay time constant. Pathological condition was simulated in accordance with the neuronal targets of the ketamine. To do this, the combination of changes was applied including the changes in the NMDA, AMPA and GABAA receptors.

RESULTS: A single administration of low-dose ketamine fleetingly reduced TC spindles and delta oscillations, amplified ongoing gamma-(30-80 Hz) and higher-frequency oscillations, and switched the firing pattern of both TC and TRN neurons from a burst mode to a single AP mode. Our computational model indicated that the firing activity of neurons in all regions including cortex, thalamus and TRN, changes from the bursting mode to the irregular non-burst spiking mode, as a result of reduced NMDA receptor activity. The simulated LFPs of CT, TRN and TC neurons under the pathological sleep condition compared to the normal sleep revealed a significant increase in the high-frequency oscillations including gamma and higher frequencies and a significant decrease in the low-frequency oscillations including spindles and the delta- and theta-frequencies in TC, TRN and CT neurons. These computational results strongly support the experimental findings.

CONCLUSION: The present findings support the hypothesis that NMDA receptor hypofunction is involved in the reduction in sleep spindles and delta oscillations.

 

Hosted by Esther Flores

 

Supported by

Carl Zeiss FoundationNeurexNeurex | InterNeuronEU Development FundEU InterregBrainLinks BrainTools

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