ИСТИНА

It is known that the brains of animals and humans is active at resting state in absence of external stimulation or functional tasks. In this paper we investigate how past experience affects characteristics of such resting state networks in animals. To do this we analyzed resting activity of 41 brain regions in intact "naive" mice and mice that were contextual fear conditioned ("training" group) 24 hours before the detection of c-Fos-positive cells in the brain. Learning has been shown to have a significant effect on the brain activity of mice at rest after 24 hours. In animals with previous experience of associative learning the number of c-Fos-positive cells was significantly increased compared to control mice in the prelimbic cortex, retrosplenial cortex, temporal associative cortex, paraventricular nucleus of the thalamus, basolateral, lateral and central amygdala nuclei. Participation in the formation of associative fear memory in both humans and animals has been shown for all these areas. Further, using the methods of correlation analysis and approaches of graph theory, we investigated the connectivity of brain areas in the resting state networks in intact and trained mice, and also reconstructed the functional resting state networks and identified their main clusters. Analysis of functional connectivity showed that learning led to significant changes in the structure of resting state networks, affecting most areas of the brain. The strength of connections between areas was generally lower in the learning group than in the naive group, and the total number of connections decreased - suggesting that having past experience of associative learning makes resting state networks more variable. If naive mice had the most resting state connections between sensory cortical areas, as well as the basal nuclei, trained animals had majority of connections in areas of the hippocampus, parahippocampal region, amygdala, associative cortices and the thalamus and to a much lesser extent in the sensory area of the cortex. The training resulted in a significant increase in amygdala functional connectivity: naive mice had only two functional connections to the three amygdala nuclei, whereas trained animals had 25 connections to other brain regions, mostly different cortical areas. We found a significant change in the structure of connections at rest after training also for the hippocampus: the number of functional connections of this area was small in intact animals, and significantly increased after training. Thus, we demonstrated for the first time the impact of past experience of associative learning on the spatial-temporal structure of resting state neural networks in the animal brain. Our findings show that associative learning can alter spontaneous brain activity and patterns of functional connections in resting state neuronal networks long after training episode. Supported by Interdisciplinary Scientific and Educational School of Moscow University «Brain, Cognitive Systems, Artificial Intelligence» and by Non-Commercial Foundation for Support of Science and Education "INTELLECT".