GABAergic parvalbumin-expressing interneurons underlie distinct local EEG microstructure during different states of unconsciousness in rats
2023
Document Type:
Conference object (Published version)
,
© 2023 by European Sleep Research Society
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Show full item recordAbstract:
Background: The GABAergic mechanism is an important target for the action of anesthetics and the promotion of sleep. We investigated the changes in
hippocampal and reticulo-thalamic nucleus (RT) GABAergic parvalbumin (PV)-expressing interneurons as possible underlying mechanisms of the different
local cortical and hippocampal EEG microstructures during NREM sleep compared with anesthesia-induced unconsciousness by two anesthetics with
different main mechanisms of action.
Methods: Twenty adult male Wistar rats were implanted for sleep recordings. After 3 hours of sleep recording, half of the rats were anesthetized with
ketamine/diazepam (100 mg/kg, i.p.) and the other half with propofol (100 mg/kg, i.p.). We recorded EEGs of the motor cortex and hippocampus during the
one-hour stable surgical phase of both anesthetics. The EEG microstructures of the motor cortex and hippocampus in local NREM sleep were compared with
their EEG microstructures during 30 minutes of unconsciousness induced by a given anesthetic. At the end of each recording under stable anesthesia, rats
were sacrificed for further PV and postsynaptic density protein 95 (PSD-95) immunohistochemistry.
Results: All three states of unconsciousness differed in motor cortical and hippocampal EEG microstructures (χ2≥9.46;p≤0.01). During propofol-induced
unconsciousness, attenuated delta and augmented sigma/beta amplitudes (z≥-4.13;p≤0.01) were the globally expressed difference, whereas increased
gamma amplitude (z=2.35;p=0.02) was the only difference at the motor-cortical level compared to NREM sleep. During ketamine/diazepam-induced
unconsciousness, attenuated theta (z≥-5.53;p≤10-4) and increased beta/gamma amplitudes (z≥-4.82;p≤10-4) were the globally expressed difference from
NREM sleep. Both anesthesia-induced unconsciousness expressed globally as increased beta amplitude (z≥-4.13;p≤10-3) and increased motor-cortical
gamma amplitude (z≥-4.20;p≤0.02) compared to NREM sleep. In contrast to propofol anesthesia, there was significant suppression of PV expression in the
hippocampus (z≤-2.71;p≤ .01) and RT during ketamine/diazepam anesthesia in all rats, but only in the hippocampus was there an inhibitory/excitatory
imbalance (increased PSD-95 expression).
Conclusions: Although anesthesia and sleep share many neurobiological features, they are distinct states in terms of local EEG microstructure and
underlying GABAergic and molecular substrate in local neuronal networks.
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
In:
- eSLEEP EUROPE; 2023 Oct 4-6; Online. European Sleep Research Society; 2023. p. 2.