title: Ð­ÐºÑÐ¿ÐµÑÐ¸Ð¼ÐµÐ½ÑÐ°Ð»ÑÐ½Ð°Ñ Ð¾ÑÐµÐ½ÐºÐ° Ð²Ð»Ð¸ÑÐ½Ð¸Ñ Ð¾Ð¿ÑÐ¾Ð³ÐµÐ½ÐµÑÐ¸ÑÐµÑÐºÐ¾Ð¹ Ð°ÐºÑÐ¸Ð²Ð°ÑÐ¸Ð¸ Ð°ÑÑÑÐ¾ÑÐ¸ÑÐ¾Ð² Ð½Ð° ÑÐ»ÐµÐºÑÑÐ¾ÑÐ¸Ð·Ð¸Ð¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÑÑ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÑ Ð½ÐµÐ¹ÑÐ¾Ð½Ð¾Ð² Ð³Ð¸Ð¿Ð¿Ð¾ÐºÐ°Ð¼Ð¿Ð°
title: Ð²ÑÐ¿ÑÑÐºÐ½Ð°Ñ ÐºÐ²Ð°Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¾Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¼Ð°Ð³Ð¸ÑÑÑÐ°
titleType: Subtitle
title: Experimental evaluation of the effect of optogenetic activation of astrocytes on the electrophysiological activity of hippocampal neurons
Creators: name: ÐÐµÑÐ°ÑÐ¸Ð¼Ð¾Ð², ÐÐ²Ð³ÐµÐ½Ð¸Ð¹
Publisher: name: Ð¡Ð°Ð½ÐºÑ-ÐÐµÑÐµÑÐ±ÑÑÐ³ÑÐºÐ¸Ð¹ Ð¿Ð¾Ð»Ð¸ÑÐµÑÐ½Ð¸ÑÐµÑÐºÐ¸Ð¹ ÑÐ½Ð¸Ð²ÐµÑÑÐ¸ÑÐµÑ ÐÐµÑÑÐ° ÐÐµÐ»Ð¸ÐºÐ¾Ð³Ð¾
Year: 2021
Subjects: ÐÐµÐ¹ÑÐ¾Ð½Ñ
Ð¾Ð¿ÑÐ¾Ð³ÐµÐ½ÐµÑÐ¸ÐºÐ°
Ð°ÑÑÑÐ¾ÑÐ¸ÑÑ
Ð³Ð¸Ð¿Ð¿Ð¾ÐºÐ°Ð¼Ð¿Ð°Ð»ÑÐ½ÑÐµ Ð½ÐµÐ¹ÑÐ¾Ð½Ñ
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opto-Î±1-Ð°Ð´ÑÐµÐ½Ð¾ÑÐµÑÐµÐ¿ÑÐ¾Ñ
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description: ÐÐ°Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¿Ð¾ÑÐ²ÑÑÐµÐ½Ð° Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ñ Ð¾ÑÐµÐ½ÐºÐ¸ Ð²Ð»Ð¸ÑÐ½Ð¸Ñ Ð¾Ð¿ÑÐ¾Ð³ÐµÐ½ÐµÑÐ¸ÑÐµÑÐºÐ¾Ð¹ Ð°ÐºÑÐ¸Ð²Ð°ÑÐ¸Ð¸ Ð°ÑÑÑÐ¾ÑÐ¸ÑÐ¾Ð², ÑÐºÑÐ¿ÑÐµÑÑÐ¸ÑÑÑÑÐ¸Ñ ÐºÐ°Ð½Ð°Ð»ÑÐ¾Ð´Ð¾Ð¿ÑÐ¸Ð½-2 Ð¸ Ð¼ÐµÑÐ°Ð±Ð¾ÑÑÐ¾Ð¿Ð½ÑÐ¹ ÐºÐ¾Ð½ÑÑÑÑÐºÑ Opto-Î±1-AR, Ð½Ð° Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÑ Ð½ÐµÐ¹ÑÐ¾Ð½Ð¾Ð² Ð³Ð¸Ð¿Ð¿Ð¾ÐºÐ°Ð¼Ð¿Ð°. ÐÐ°Ð´Ð°ÑÐ¸, ÐºÐ¾ÑÐ¾ÑÑÐµ ÑÐµÑÐ°Ð»Ð¸ÑÑ Ð² ÑÐ¾Ð´Ðµ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ñ: 1) ÐÑÐ±Ð¾Ñ Ð¿Ð°ÑÐ°Ð¼ÐµÑÑÐ¾Ð² ÑÐ²ÐµÑÐ¾Ð²Ð¾Ð¹ Ð°ÐºÑÐ¸Ð²Ð°ÑÐ¸Ð¸ Ð½Ð° Ð¾ÑÐ½Ð¾Ð²Ðµ Ð°Ð½Ð°Ð»Ð¸Ð·Ð° ÑÐ¿Ð¾Ð½ÑÐ°Ð½Ð½Ð¾Ð¹ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ Ð½ÐµÐ¹ÑÐ¾Ð½Ð¾Ð² Ð³Ð¸Ð¿Ð¿Ð¾ÐºÐ°Ð¼Ð¿Ð° Ð°ÑÑÐ±ÑÐ¸Ð´Ð½ÑÑ Ð¼ÑÑÐµÐ¹-Ð°Ð»ÑÐ±Ð¸Ð½Ð¾ÑÐ¾Ð² Ð¿ÑÐ¸ Ð¾Ð¿ÑÐ¾Ð³ÐµÐ½ÐµÑÐ¸ÑÐµÑÐºÐ¾Ð¹ Ð°ÐºÑÐ¸Ð²Ð°ÑÐ¸Ð¸ Ð°ÑÑÑÐ¾ÑÐ¸ÑÐ¾Ð², ÑÐºÑÐ¿ÑÐµÑÑÐ¸ÑÑÑÑÐ¸Ñ ChR2 Ð¸Ð»Ð¸ Opto-Î±1AR. 2) Ð ÐµÐ³Ð¸ÑÑÑÐ°ÑÐ¸Ñ Ð¸ Ð°Ð½Ð°Ð»Ð¸Ð· Ð¿ÐÐÐ¡Ð Ð² Ð¿ÐµÑÐµÐ¶Ð¸Ð²Ð°ÑÑÐ¸Ñ ÑÑÐµÐ·Ð°Ñ Ð³Ð¸Ð¿Ð¿Ð¾ÐºÐ°Ð¼Ð¿Ð° Ð¼ÑÑÐµÐ¹-Ð¼Ð¾Ð´ÐµÐ»ÐµÐ¹ Ð±Ð¾Ð»ÐµÐ·Ð½Ð¸ ÐÐ»ÑÑÐ³ÐµÐ¹Ð¼ÐµÑÐ° (5xFAD) Ð¸ Ð¼ÑÑÐµÐ¹ Ð´Ð¸ÐºÐ¾Ð³Ð¾ ÑÐ¸Ð¿Ð° (WT) Ð´Ð¾ Ð¸ Ð¿Ð¾ÑÐ»Ðµ Ð¾Ð¿ÑÐ¾Ð³ÐµÐ½ÐµÑÐ¸ÑÐµÑÐºÐ¾Ð¹ ÑÑÐ¸Ð¼ÑÐ»ÑÑÐ¸Ð¸ Ð°ÑÑÑÐ¾ÑÐ¸ÑÐ¾Ð², ÑÐºÑÐ¿ÑÐµÑÑÐ¸ÑÑÑÑÐ¸Ñ Ð¸Ð¾Ð½Ð¾ÑÑÐ¾Ð¿Ð½ÑÐ¹ Ð¾Ð¿ÑÐ¸Ð½. 3) Ð ÐµÐ³Ð¸ÑÑÑÐ°ÑÐ¸Ñ Ð¸ Ð°Ð½Ð°Ð»Ð¸Ð· Ð¿ÐÐÐ¡Ð Ð² Ð¿ÐµÑÐµÐ¶Ð¸Ð²Ð°ÑÑÐ¸Ñ ÑÑÐµÐ·Ð°Ñ Ð³Ð¸Ð¿Ð¿Ð¾ÐºÐ°Ð¼Ð¿Ð° Ð¼ÑÑÐµÐ¹-Ð¼Ð¾Ð´ÐµÐ»ÐµÐ¹ Ð±Ð¾Ð»ÐµÐ·Ð½Ð¸ ÐÐ»ÑÑÐ³ÐµÐ¹Ð¼ÐµÑÐ° (5xFAD) Ð¸ Ð¼ÑÑÐµÐ¹ Ð´Ð¸ÐºÐ¾Ð³Ð¾ ÑÐ¸Ð¿Ð° (WT) Ð´Ð¾ Ð¸ Ð¿Ð¾ÑÐ»Ðµ Ð¾Ð¿ÑÐ¾Ð³ÐµÐ½ÐµÑÐ¸ÑÐµÑÐºÐ¾Ð¹ ÑÑÐ¸Ð¼ÑÐ»ÑÑÐ¸Ð¸ Ð°ÑÑÑÐ¾ÑÐ¸ÑÐ¾Ð², ÑÐºÑÐ¿ÑÐµÑÑÐ¸ÑÑÑÑÐ¸Ñ Ð¼ÐµÑÐ°Ð±Ð¾ÑÑÐ¾Ð¿Ð½ÑÐ¹ Ð¾Ð¿ÑÐ¸Ð½. Ð Ð°Ð±Ð¾ÑÐ° Ð¿ÑÐ¾Ð²ÐµÐ´ÐµÐ½Ð° Ð½Ð° Ð±Ð°Ð·Ðµ ÐÐ°Ð±Ð¾ÑÐ°ÑÐ¾ÑÐ¸Ð¸ ÐÐ¾Ð»ÐµÐºÑÐ»ÑÑÐ½Ð¾Ð¹ Ð½ÐµÐ¹ÑÐ¾Ð´ÐµÐ³ÐµÐ½ÐµÑÐ°ÑÐ¸Ð¸ (ÐÐÐ), Ð³Ð´Ðµ ÑÐ¾Ð±Ð¸ÑÐ°Ð»Ð°ÑÑ Ð²ÑÑ ÑÐ°ÐºÑÐ¸ÑÐµÑÐºÐ°Ñ ÑÐ°ÑÑÑ ÑÐµÐ·ÑÐ»ÑÑÐ°ÑÐ¾Ð². Ð ÑÐµÐ·ÑÐ»ÑÑÐ°ÑÐµ Ð¾ÑÐµÐ½ÐºÐ¸ Ð²Ð»Ð¸ÑÐ½Ð¸Ñ Ð¾Ð¿ÑÐ¾Ð³ÐµÐ½ÐµÑÐ¸ÑÐµÑÐºÐ¾Ð¹ Ð°ÐºÑÐ¸Ð²Ð°ÑÐ¸Ð¸ Ð°ÑÑÑÐ¾ÑÐ¸ÑÐ¾Ð² Ð½Ð° Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÑ Ð½ÐµÐ¹ÑÐ¾Ð½Ð¾Ð² Ð³Ð¸Ð¿Ð¿Ð¾ÐºÐ°Ð¼Ð¿Ð° Ð±ÑÐ»Ð¾ Ð¿Ð¾Ð»ÑÑÐµÐ½Ð¾, ÑÑÐ¾ Ð½Ð°Ð¸Ð±Ð¾Ð»ÑÑÐµÐµ ÑÐ²ÐµÐ»Ð¸ÑÐµÐ½Ð¸Ðµ ÐºÐ¾Ð»Ð¸ÑÐµÑÑÐ²Ð° ÑÐ¿Ð¾Ð½ÑÐ°Ð½Ð½ÑÑ ÑÐ¾ÐºÐ¾Ð² Ð½Ð°Ð±Ð»ÑÐ´Ð°ÐµÑÑÑ Ð¿ÑÐ¸ Ð°ÐºÑÐ¸Ð²Ð°ÑÐ¸Ð¸ Ð°ÑÑÑÐ¾ÑÐ¸ÑÐ¾Ð², ÑÐºÑÐ¿ÑÐµÑÑÐ¸ÑÑÑÑÐ¸Ñ ChR2, ÑÐµÐ¶Ð¸Ð¼Ð¾Ð¼ 5 ÑÐµÐºÑÐ½Ð´ Ð½ÐµÐ¿ÑÐµÑÑÐ²Ð½Ð¾Ð³Ð¾ ÑÐ²ÐµÑÐ°, Ð° Ð´Ð»Ñ Ð¼ÐµÑÐ°Ð±Ð¾ÑÑÐ¾Ð¿Ð½Ð¾Ð³Ð¾ Ð¾Ð¿ÑÐ¸Ð½Ð° â T=1 Ñ, t=100 Ð¼Ñ Ð² Ð¸Ð¼Ð¿ÑÐ»ÑÑÐ½Ð¾Ð¼ ÑÐµÐ¶Ð¸Ð¼Ðµ. ÐÐ¿ÑÐµÐ´ÐµÐ»ÐµÐ½Ð¾, ÑÑÐ¾ Ð°ÐºÑÐ¸Ð²Ð°ÑÐ¸Ñ Opto-Î±1AR Ð¿ÑÐ¸Ð²Ð¾Ð´Ð¸Ñ Ðº ÑÐ²ÐµÐ»Ð¸ÑÐµÐ½Ð¸Ñ ÑÐ³Ð»Ð° Ð½Ð°ÐºÐ»Ð¾Ð½Ð° Ð¿ÐÐÐ¡Ð. ÐÐ° Ð¾ÑÐ½Ð¾Ð²Ð°Ð½Ð¸Ð¸ Ð¿ÑÐ¾Ð²ÐµÐ´ÐµÐ½Ð½ÑÑ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ð¹ Ð±ÑÐ»Ð¾ ÑÑÑÐ°Ð½Ð¾Ð²Ð»ÐµÐ½Ð¾, ÑÑÐ¾ Ð´Ð»Ñ ÑÐµÐ»ÐµÐ¹ Ð°ÐºÑÐ¸Ð²Ð°ÑÐ¸Ð¸ Ð½ÐµÐ¹ÑÐ¾Ð½Ð°Ð»ÑÐ½Ð¾Ð¹ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ Ð¿ÑÐµÐ´Ð¿Ð¾ÑÑÐ¸ÑÐµÐ»ÑÐ½ÐµÐµ Ð¸ÑÐ¿Ð¾Ð»ÑÐ·Ð¾Ð²Ð°ÑÑ Ð¼ÐµÑÐ°Ð±Ð¾ÑÑÐ¾Ð¿Ð½ÑÐµ Ð¾Ð¿ÑÐ¸Ð½Ñ Ð¸ Ð¿ÑÐ¸Ð¼ÐµÐ½ÐµÐ½Ð¸Ðµ Opto-a1AR, ÑÐºÑÐ¿ÑÐµÑÑÐ¸ÑÐ¾Ð²Ð°Ð½Ð½Ð¾Ð³Ð¾ Ð² Ð°ÑÑÑÐ¾ÑÐ¸ÑÐ°Ñ Ð³Ð¸Ð¿Ð¿Ð¾ÐºÐ°Ð¼Ð¿Ð°, Ð¸Ð¼ÐµÐµÑ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»ÑÐ½ÑÐ¹ ÑÑÑÐµÐºÑ Ð´Ð»Ñ Ð²Ð¾ÑÑÑÐ°Ð½Ð¾Ð²Ð»ÐµÐ½Ð¸Ñ Ð´Ð¾Ð»Ð³Ð¾Ð²ÑÐµÐ¼ÐµÐ½Ð½Ð¾Ð¹ Ð¿Ð»Ð°ÑÑÐ¸ÑÐ½Ð¾ÑÑÐ¸ Ñ Ð¼ÑÑÐµÐ¹ Ñ Ð³ÐµÐ½ÐµÑÐ¸ÑÐµÑÐºÐ¾Ð¹ Ð¼Ð¾Ð´ÐµÐ»ÑÑ Ð·Ð°Ð±Ð¾Ð»ÐµÐ²Ð°Ð½Ð¸Ñ ÐÐ»ÑÑÐ³ÐµÐ¹Ð¼ÐµÑÐ° Ð¸ ÑÐ¿Ð¾ÑÐ¾Ð±Ð½Ð¾ ÑÐ»ÑÑÑÐ¸ÑÑ Ð¸Ñ ÑÐµÐ·ÑÐ»ÑÑÐ°ÑÑ Ð² Ð¿Ð¾Ð²ÐµÐ´ÐµÐ½ÑÐµÑÐºÐ¸Ñ ÑÐµÑÑÐ°Ñ.
description: This work is devoted to the evaluation of the effect of optogenetic activation of astrocytes expressing channelrodopsin-2 and the metabotropic construct Opto-Î±1-AR on the activity of hippocampal neurons. Tasks that were solved in the course of the study: 1) Selection of light activation parameters based on the analysis of spontaneous activity of hippocampal neurons in albino outbrid mice during optogenetic activation of astrocytes expressing ChR2 or Opto-a1AR. 2) Registration and analysis of fEPSP in acute hippocampal slices of Alzheimer's disease model mice (5xFAD) and wild-type mice (WT) before and after optogenetic stimulation of astrocytes expressing ionotropic opsin. 3) Registration and analysis of fEPSP in acute hippocampal slices of Alzheimer's disease model mice (5xFAD) and wild-type mice (WT) before and after optogenetic stimulation of astrocytes expressing metabotropic opsin. The work was carried out on the basis of the Laboratory of Molecular Neurodegeneration (LMN), where all the actual results were collected. As a result of the evaluation of the effect of optogenetic activation of astrocytes on the activity of hippocampal neurons, it was found that the greatest increase in the number of spontaneous currents is observed when astrocytes expressing ChR2 are activated in the mode of 5 seconds of continuous light, and for metabotropic opsin â T=1 s, t=100 ms in the pulse mode. It is found that the activation of Opto-a1AR leads to an increase in the fEPSP slope. Based on the studies conducted, it was found that metabotropic opsins are preferable for the activation of neuronal activity, and the use of Opto-a1AR expressed in hippocampal astrocytes has a potential effect for restoring long-term plasticity in mice with a genetic model of Alzheimer's disease and can improve their results in behavioral tests.