Modeling the effect of ethanol and GABAergic transmission blockers on the generation of hypocampal theta-rhythm

Lagosha.S.V., Soldatova A.E.1, Semyanov A.V., Brazhe A.R.

Lomonosov Moscow State University, Faculty of Biology, Department of Biophysics, Russia, 119234, Moscow, Leninskie Gory, 1 p. 24, e-mail:

1State Scientific Center Federal State Budgetary Institution of Science Institute of Bioorganic Chemistry named after Academicians M.M. Shemyakin and Yu.A. Ovchinikova of the Russian Academy of Sciences, 117997, Moscow, Miklukho-Maklaya str., Russia, 16/10.

Synchronization of the activity of groups of neurons in different brain structures, leads to the induction of macroscopic periodic oscillations of the electric field, which can be registered using electrodes. At the same time, different frequency bands of the electrical activity have different physiological functions and correlate with different behavioral patterns. In this study, we used implantable extracellular electrodes to register theta rhythm, which is determined by synchronized synaptic activity on pyramidal hippocampal neurons with a frequency of 4 to 12 Hz. Mice (C57BL\6) acted as a model organisms with electrodes installed bilaterally in the hippocampal zones CA1 and CA3.

We investigated the effect of blockers of extrasynaptic GABA-dependent transmission (picrotoxin) and ethanol on theta rhythm in various areas of the hippocampus of freely moving animals.

Low concentrations of picrotoxin (1 μM) have little effect on the characteristics of the theta rhythm. An increase in concentration to 10 μM leads to a shortening of theta rhythm episodes, a significant decrease in frequency and power. Exposure to ethanol vapors has a sedative effect on mice, at the end of exposure reducing the main frequency of the rhythm to 2-4 Hz and suppressing locomotion. The effect is enhanced by the combined action of ethanol and picrotoxin.

The obtained results were partially reproduced using the model of an ensemble of neurons in the BRIAN 2 modeling environment, the membrane potential equations were described by the Hodgkin-Huxley formalism. The model describes a set of neurons and astrocytes of the CA3 region of the hippocampus. We used the previously presented approach, which allows us to quantitatively and qualitatively characterize rhythmic activity based on the recording of the local field potential (LFP) and its wavelet-transform.

A significant dependence between the concentration of extracellular potassium, intra-astrocytic chlorine and the equilibrium concentration of extracellular GABA based on the proposed GAT3 transporter model was shown. The simulation results are consistent with the latest literature data [1]. The importance of spatial organization of neurons in generating specific responses to stimulation has been confirmed [2]. The proposed model will be validated on experimental data.


1. Untiet V. et al. Astrocytic chloride is brain state dependent and modulates inhibitory neurotransmission in mice //Nature Communications. – 2023. – Т. 14. – №. 1. – С. 1871.

2. Aussel A. et al. A detailed anatomical and mathematical model of the hippocampal formation for the generation of sharp-wave ripples and theta-nested gamma oscillations //Journal of Computational Neuroscience. – 2018. – Т. 45. – С. 207-221.

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