Modulation of spatial memory and expression of hippocampal neurotransmitter receptors by selective lesion of medial sept

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RESEARCH ARTICLE

Modulation of spatial memory and expression of hippocampal neurotransmitter receptors by selective lesion of medial septal cholinergic and GABAergic neurons Manana G. Dashniani1   · Maia A. Burjanadze1   · Nino C. Chkhikvishvili1   · Revaz O. Solomonia1,2 · Manana Kandashvili2   · Temur L. Naneishvili1   · Gela V. Beselia1,3   · Lali B. Kruashvili1   · Mariam R. Chighladze1  Received: 11 March 2020 / Accepted: 20 July 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

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 septohippocampal 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. Keywords  Spatial memory · Medial septum · Hippocampal receptors · Rat

Introduction

Communicated by Sreedharan Sajikumar. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0022​1-020-05889​-6) contains supplementary material, which is available to authorized users. * Manana G. Dashniani [email protected] 1



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

2



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

3

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



The role of hippocampus in various aspects of cognitive function, including learning and spatial memory, has been pointed out by extensive clinical and experimental data (Morris et al. 1982; Broadbent et al. 2004; Morgado-Bernal 2011). The various neurotransmitter systems within the hippocampal formation—glutamate, gamma-aminobutyric acid (GABA) and acetylcholine (ACh)—are of special importance in learning process and memory formati