MEMORY CONSOLIDATION IS GOVERNED BY GAP JUNCTIONAL COMMUNICATION IN THE ASTROCYTIC NETWORK
01/30/2020
Márton Péter1, Zsolt Szabó1, László Héja1
1 Functional Pharmacology Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, Budapest
There is a growing body of evidence for the involvement of astrocytes in oscillatory brain activity, both in physiological and pathophysiological processes. By exploring various molecular interactions between neuronal and astrocyte networks, we have previously shown that blocking astrocytic gap junctions suppresses slow wave activity in rats, suggesting a causal role of astrocytes in neuronal synchronization (Szabó et al. 2017). Since slow wave sleep is associated with memory consolidation, perturbation of the astrocytic syncytium during this process may impact the working memory of rats. In this, we activated astrocytic gap junctions using trimethylamine (TMA), or inhibited them with an astrocyte-specific connexin 43 (Cx43) antibody (5μl, 0.75mg/ml). Local field potential measurements along with parallel electromyography were used to explore the effect on neuronal slow-wave sleep correlates. Memory consolidation was evaluated using novel object recognition tests. Our results show that the opening of gap junctions by TMA significantly enhances memory formation, while inhibition by Cx43 antibody impairs memory performance. We conclude that large-scale synchronization in the astrocyte network through gap junctions play a previously unrecognized, essential role in higher cognitive functions and may open up new avenues in the therapy of cognitive disorders. This work was supported by grants VEKOP-2.1.1-15-2016-00156 and National Research, Development and Innovation Office grant OTKA K124558. References: Szabó, Z., Héja, L., Szalay, G., Kékesi, O., Füredi, A., Szebényi, K., Dobolyi, Á., Orbán, T.I., Kolacsek, O., Tompa, T. and Miskolczy, Z., 2017. Extensive astrocyte synchronization advances neuronal coupling in slow wave activity in vivo. Scientific Reports, 7(1), p.6018.