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Modulation of spatial memory and expression of hippocampal neurotransmitter receptors by selective lesion of medial septal cholinergic and GABAergic neurons

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Abstract

The medial septum (MS) is an important modulator of hippocampal function. The degree of damage in which the particular set of septo-hippocampal projections contributes to the deficits of spatial memory with concomitant changes of hippocampal receptors expression has not been studied till present. Therefore, we investigated spatial memory and the expression level of cholinergic (α7 nACh and M1), GABAergic (α1 subunit of GABAA) and glutamatergic (NR2B subunit of NMDA and GluR 1 subunit of AMPA) receptors in the hippocampus following selective lesions of cholinergic and GABAergic septo-hippocampal projection. Learning process and long-term spatial memory were assessed using a Morris water maze. The obtained results revealed that in contrast to cholinergic lesions, rats with MS GABAergic lesions exhibit a retention deficit in 3 days after training. Western blot analyses revealed the MS cholinergic lesions have significant effect on the expression level of the M1 mACh receptors, while MS GABAergic lesions induce dramatic modulations of hippocampal glutamatergic, cholinergic and GABAergic receptors expression. These results for the first time demonstrated that selective lesions of MS cholinergic and GABAergic neurons differentially affect long-term spatial memory and the memory deficit after MS GABAergic lesion is paralleled with significant changes of hippocampal glutamate, GABA and acetylcholine receptors expression.

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Funding

The design of this study, analysis, interpretation of data and manuscript preparation were supported by the funding from the Shota Rustaveli National Science Foundation of Georgia (SRNSFG): Grant—13/10. The data collection for immunochemical studies was supported by the funding from SRNSFG: Grant YS15_2.3.1_51.

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Authors and Affiliations

  1. Department of Behavior and Cognitive Function, I. Beritashvili Center of Experimental Biomedicine, 0160, Tbilisi, Georgia

    Manana G. Dashniani, Maia A. Burjanadze, Nino C. Chkhikvishvili, Revaz O. Solomonia, Temur L. Naneishvili, Gela V. Beselia, Lali B. Kruashvili & Mariam R. Chighladze

  2. Institute of Chemical Biology, Ilia State University, 0162, Tbilisi, Georgia

    Revaz O. Solomonia & Manana Kandashvili

  3. Department of Physiology and Pharmacology, Petre Shotadze Tbilisi Medical Academy, 0144, Tbilisi, Georgia

    Gela V. Beselia

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  1. Manana G. Dashniani
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  2. Maia A. Burjanadze
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  3. Nino C. Chkhikvishvili
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  5. Manana Kandashvili
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  6. Temur L. Naneishvili
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  9. Mariam R. Chighladze
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Contributions

MD and MB contributed to the conception and design; MD, MB and RS contributed to analysis and interpretation of data in the manuscript; GB, LK, NC, MC, and MK managed the data collection. Statistical analysis was done by MD, RS and MB. RS and TN revised the manuscript. All authors declare the responsibility for every aspect of the work. All authors read and approved the final manuscript.

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Correspondence to Manana G. Dashniani.

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The authors declare that there are no conflicts of interest regarding the publication of this paper.

Ethical approval

All experimental procedures were conducted in accordance with the European Communities Council Directive Guidelines for the care and use of laboratory animals (2010/63/EU—European Commission) and approved by the animal care and use committee at the I. Beritashvili Center of Experimental Biomedicine.

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Communicated by Sreedharan Sajikumar.

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Dashniani, M.G., Burjanadze, M.A., Chkhikvishvili, N.C. et al. Modulation of spatial memory and expression of hippocampal neurotransmitter receptors by selective lesion of medial septal cholinergic and GABAergic neurons. Exp Brain Res 238, 2385–2397 (2020). https://doi.org/10.1007/s00221-020-05889-6

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