Title
Inhibitory Neurons Exhibit High Controlling Ability In The Cortical Microconnectome
Abstract
The brain is a network system in which excitatory and inhibitory neurons keep activity balanced in the highly non-random connectivity pattern of the microconnectome. It is well known that the relative percentage of inhibitory neurons is much smaller than excitatory neurons in the cortex. So, in general, how inhibitory neurons can keep the balance with the surrounding excitatory neurons is an important question. There is much accumulated knowledge about this fundamental question. This study quantitatively evaluated the relatively higher functional contribution of inhibitory neurons in terms of not only properties of individual neurons, such as firing rate, but also in terms of topological mechanisms and controlling ability on other excitatory neurons. We combined simultaneous electrical recording (similar to 2.5 hours) of similar to 1000 neurons in vitro, and quantitative evaluation of neuronal interactions including excitatory-inhibitory categorization. This study accurately defined recording brain anatomical targets, such as brain regions and cortical layers, by inter-referring MRI and immunostaining recordings. The interaction networks enabled us to quantify topological influence of individual neurons, in terms of controlling ability to other neurons. Especially, the result indicated that highly influential inhibitory neurons show higher controlling ability of other neurons than excitatory neurons, and are relatively often distributed in deeper layers of the cortex. Furthermore, the neurons having high controlling ability are more effectively limited in number than central nodes of k-cores, and these neurons also participate in more clustered motifs. In summary, this study suggested that the high controlling ability of inhibitory neurons is a key mechanism to keep balance with a large number of other excitatory neurons beyond simple higher firing rate. Application of the selection method of limited important neurons would be also applicable for the ability to effectively and selectively stimulate E/I imbalanced disease states.Author summaryHow small numbers of inhibitory neurons functionally keep balance with large numbers of excitatory neurons in the brain by controlling each other is a fundamental question. Especially, this study quantitatively evaluated a topological mechanism of interaction networks in terms of controlling abilities of individual cortical neurons to other neurons. Combination of simultaneous electrical recording of similar to 1000 neurons and a quantitative evaluation method of neuronal interactions including excitatory-inhibitory categories, enabled us to evaluate the influence of individual neurons not only about firing rate but also about their relative positions in the networks and controllable ability of other neurons. Especially, the result showed that inhibitory neurons have more controlling ability than excitatory neurons, and such neurons were more often observed in deep layers. Because the limited number of neurons in terms controlling ability were much smaller than neurons based on centrality measure and, of course, more directly selected neurons based on their ability to control other neurons, the selection method of important neurons will help not only to produce realistic computational models but also will help to stimulate brain to effectively treat imbalanced disease states.
Year
DOI
Venue
2021
10.1371/journal.pcbi.1008846
PLOS COMPUTATIONAL BIOLOGY
DocType
Volume
Issue
Journal
17
4
ISSN
Citations 
PageRank 
1553-734X
0
0.34
References 
Authors
0
7