Information in the brain doesn’t just zip through the individual brain cell connections as private signals – there’s much more happening, especially outside the cells. Chemical messengers travel through the fluid surrounding them, informing volumes of the brain rather than individual recipient cells. Many cell types, agents and signal paths participate in what is termed the connectome, the entirety of all connections in the brain. Researchers seek to map the connectome as the next step towards understanding how the brain functions.
By Diego Guidolin and Luigi F. Agnati
Cellular network architecture plays a crucial role as the structural substrate for the brain functions, leading to a concerted dynamic where it is difficult and sometimes impossible, to assign tightly defined and unique roles to each specific component of the system. Therefore, it represents the main rationale for the emerging field of connectomics, defined as the comprehensive study of all aspects of central nervous system connectivity.
In their research article published in the journal Reviews in the Neurosciences, scientists from the University of Karolinska Institute in Sweden and the University of Padova, Italy focused mainly on the communication between neurons and demonstrated many nontrivial features of the neuronal networks.
In their article, the main emphasis centers on a wider spectrum of communication processes in the brain, namely wiring transmission (WT, communication via private channels, e.g. synaptic transmission and gap junctions) and volume transmission (VT, signal diffusion along the extracellular fluid pathways;), also involving cell types other than neurons.
Considering both processes can further expand the connectomics concept, since both WT and VT modes of communication contribute to the structure of the brain network. A consensus exists that such a structure follows a hierarchical or nested architecture: inter-areas macroscale and inter-cellular microscales have been defined.
In this respect, however, several lines of evidence indicate that a molecular level should also be considered to capture direct protein-protein allosteric interactions, such as those occurring in receptor-receptor interactions at the plasma membrane level, since they can play a role in resetting the synaptic efficacy and in memory processes.
In addition, emerging evidence points to novel mechanisms likely playing a significant role in the modulation of intercellular connectivity, increasing the plasticity (i.e. the experience-based reshaping) of the system. Of particular interest is the intercellular transfer of RNA, proteins and receptors by extracellular vesicles since it allows the transient acquisition by a nerve cell of new signal release capabilities and/or new recognition/decoding apparatuses.
Relevant implications for neurophysiology, neuropathology and neuropharmacology can be derived from this enlarged view on CNS organization and intercellular communication modes.
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