The emergence of the volume transmission concept1

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Abstract

Interneuronal communication in the central nervous system (CNS) have always been of basic importance for theories on the cerebral morphofunctional architecture. Our group has proposed that intercellular communication in the brain can be grouped into 2 broad classes based on some general features of the transmission: wiring (WT) and volume (VT) transmission. WT occurs via a relatively constrained cellular chain (wire), while VT consists of 3-dimensional diffusion of signals in the extracellular fluid (ECF) for distances larger than the synaptic cleft. Both morphological and functional evidence indicates that dopamine (DA) synapses in striatum are `open' synapses, i.e., synapses which favor diffusion of the transmitter into the surrounding ECF and observations are compatible with the view that DA varicosities can synthesize, store and release DA for VT. The DAergic mesostriatal transmission has, therefore, been examined by several groups to give experimental support to VT. Moreover, due to its minor structural requirements, VT may become prevalent under some pathological conditions, e. g. Parkinson's disease. In animal models of DAergic pathway degeneration, it has been shown that a compensatory activation of surviving DA terminals may lead to a preferential potentiation of VT. WT and VT favor different and complementary types of computation. VT is markedly slower and less safe than WT, but has minor spatial constraints and allows the reach of a large number of targets. Models of neuronal systems integrating classical neuronal circuits and diffusible signals begin to show how WT and VT may interact in the neural tissue.

Section snippets

Modes of intercellular communication in the central nervous system: the concept of wiring and volume transmission

As beautifully discussed in Jacobson's book Foundations of Neuroscience [47]and Shepherd's book Foundations of the Neuron Doctrine [73], connectivity and communication between the cellular elements building up the central nervous system (CNS), have always been of basic importance for theories on the morphofunctional architecture of the brain. At the turn of this century two main opposing views on these issues were competing with each other: Cajal's neuron doctrine and Golgi's reticular theory.

The dopaminergic mesostriatal pathway as a model system for VT

From the list of VT basic elements reported above, it is evident that this type of intercellular communication may be present in many central neural systems and have very different features according to the cell structures (sources and targets) and chemical nature of VT signal involved in the communication process as well as the characteristics of the ECF pathways. Model systems for VT are the highly divergent monoaminergic pathways of the brain, e.g., the dopaminergic mesostriatal system. Both

Classification of intercellular communication modes in the frame of the WT and VT concepts

Besides the few examples reported above, a wealth of data support the existence of VT in the mammalian brain (see Refs. 4, 84for recent reviews). They comprise evidence of transmitters released by non-neuronal cells (such as glial GABA and glutamate), transmitters which are not limited by cell barriers (such as gases), transmitters released by extrasynaptic sites (e.g., most neuropeptides), etc. An attempt to classify the different classes of VT has been recently made in the frame of a

Differential functional features of WT and VT: models of VT-based computation

As pointed out in this and previous papers 1, 2, 3, 4, 5, 29, 30, 31, 84intercellular transfer of information via WT or VT is clearly different. At first sight, VT has several drawbacks over WT, since it is markedly slower (Table 2) and less safe (as it can be influenced by many sources of noise present in the ECF). However, a more penetrating analysis shows that VT and WT are in fact complementary and suited for different functions (Table 3). For instance, VT is not dependent on the existence

Acknowledgements

The experimental work described in this paper was supported by italian MURST and CNR grants.

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