Information handling by the brain: proposal of a new “paradigm” involving the roamer type of volume transmission and the tunneling nanotube type of wiring transmission

Abstract

The current view on the organization of the central nervous system (CNS) is basically anchored to the paradigm describing the brain as formed by networks of neurons interconnected by synapses. Synaptic contacts are a fundamental characteristic for describing CNS operations, but increasing evidence accumulated in the last 30 years pointed to a refinement of this view. A possible overcoming of the classical "neuroscience paradigm" will be here outlined, based on the following hypotheses: (1) the basic morpho-functional unit in the brain is a compartment of tissue (functional module) where different resident cells (not only neurons) work as an integrated unit; (2) in these complex networks, a spectrum of intercellular communication processes is exploited, that can be classified according to a dichotomous criterion: wiring transmission (occurring through physically delimited channels) and volume transmission (exploiting diffusion in the extracellular space); (3) the connections between cells can themselves be described as a network, leading to an information processing occurring at different levels from cell network down to molecular level; (4) recent evidence of the existence of specialized structures (microvesicles and tunneling nanotubes) for intercellular exchange of materials, could allow a further type of polymorphism of the CNS networks based on at least transient changes in cell phenotype. When compared to the classical paradigm, the proposed scheme of cellular organization could allow a strong increase of the degrees of freedom available to the whole system and then of its plasticity. Furthermore, long range coordination and correlation can be more easily accommodated within this framework.

G protein-coupled receptor-receptor interactions give integrative dynamics to intercellular communication

“…Different types of MV have been described (see Agnati et al, 2014), but two types are of importance for our discussion. Exosomes are vesicles (40-100 nm in diameter) contained in the so-called early, late, or recycling endosomes, a type of multivesicular bodies.…”

On the role of the extracellular space on the holistic behavior of the brain

“…The basic dichotomous classification of intercellular communication in the brain proposed almost three decades ago (Agnati et al, 1986; see also Agnati and Fuxe, 2000) can also easily accommodate recent evidence concerning the existence of other specialized structures for intercellular communication, such as micro-vesicles for a well-demonstrated VT type ) and tunneling nanotubes for a WT that is not yet in vivo demonstrated in the brain (Rustom et al, 2004). Thus, recently a more complete classification has been suggested for both VT and WT (see Agnati et al, 2010aAgnati et al, , 2014. As far as the VT is concerned, the distinction has been proposed between 'classical VT' (migration of chemical and physical signals) and roamer type of VT (RT-VT) (migration of micro-vesicles, see below).…”

“…In particular, it has allowed us to introduce the concept of CCNs (Agnati and Fuxe, 2000), i.e., the set of cells of any type, which by exploiting the entire spectrum of intercellular communication modes are capable of integrating multiple inputs to give out appropriate outputs and to support each other's survival (Agnati and Fuxe, 2000;Agnati et al, 2014). It can be surmised that an interplay between astrocytes and neurons occurs in organizing the CCNs especially via astrocytic release of gliotransmitters that are similar to known neurotransmitters and interact with target receptors similar to those targeted by neurotransmitters.…”

Two emerging topics regarding long-range physical signaling in neurosystems: Membrane nanotubes and electromagnetic fields

“…VT is also known as "nonsynaptic diffusion neurotransmission" (Bach-Y-Rita, 1993Kercel, 2004). In a recently published paper, Agnati et al (2014) highlighted that two newly discovered signal transmission types in the brain seem to be of significant importance to further understand the function of the brain: signaling via (i) membrane nanotubes (a new form of WT), and (ii) via extracellular vesicles (a new form of VT). Agnati et al conclude that "their importance in integrative actions is potentially enormous" (Agnati et al, 2014).…”

“…In a recently published paper, Agnati et al (2014) highlighted that two newly discovered signal transmission types in the brain seem to be of significant importance to further understand the function of the brain: signaling via (i) membrane nanotubes (a new form of WT), and (ii) via extracellular vesicles (a new form of VT). Agnati et al conclude that "their importance in integrative actions is potentially enormous" (Agnati et al, 2014). In parallel, more and more research is showing that endogenous electromagnetic fields play a fundamental role, and it is concluded that "endogenous brain activity can causally affect neural function through field effects under physiological conditions" (Anastassiou et al, 2011).…”