Connectivity of the Brain in the Light of Chemogenetic Modulation of Neuronal Activity

Connectivity is the coordinated activity of the neuronal networks responsible for brain functions; it is detected based on functional magnetic resonance imaging signals that depend on the oxygen level in the blood (blood oxygen level-dependent (BOLD) signals) supplying the brain. The BOLD signal is only indirectly related to the underlying neuronal activity; therefore, it remains an open question whether connectivity and changes in it are only manifestations of normal and pathological states of the brain or they are, to some extent, the causes of these states. The creation of chemogenetic receptors activated by synthetic drugs (designer receptors exclusively activated by designer drugs, DREADDs), which, depending on the receptor type, either facilitate or, on the contrary, inhibit the neuronal response to received physiological stimuli, makes it possible to assess brain connectivity in the light of controlled neuronal activity. Evidence suggests that connectivity is based on neuronal activity and is a manifestation of connections between brain regions that integrate sensory, cognitive, and motor functions. Chemogenetic modulation of the activity of various groups and types of neurons changes the connectivity of the brain and its complex functions. Chemogenetics can be useful in reconfiguring the pathological mechanisms of nervous and mental diseases. The initiated integration, based on the whole-brain connectome from molecular-cellular, neuronal, and synaptic processes to higher nervous activity and behavior, has the potential to significantly increase the fundamental and applied value of this branch of neuroscience.