L.D. Surgical Pathology University "La Sapienza" of Rome

MD - General Surgeon, Sydney, NSW


Biological Evolution Dpt. - University of Parma, Italy

Pubblicato su ;Rivista di Biologia,Biology Forum91(1998)pp.329-334


KEY WORDS Consciousness Cortex Mediator molecules Presynaptic and postsynaptic membrane USC (SUC) - Unified Synaptic Channel (Synaptic Unified Channel)


We believe that it would be inappropriate, on account of the nature of this work, to recall the detailed structure of the cortical brain and of neuronal synapses. However, we consider it necessary to examine a few fundamental anatomical items. A single cell of the cerebral cortex, let's say a pyramidal neuron of the 5th layer, is literally saturated with synapses connecting it to numerous other nearby neurons. The number of such synapses ranges from a few hundreds up to 20.000 or more for each neuron [1], so that they can be imagined to be densely packed around the soma, the dendrites and in some cases the axon itself. In our hypothesis, being each synapse adjacent and at any rate close to the next, all the single synaptic fissures should no longer be considered as separate entities; rather, they could be regarded as merging together in a channel-like structure extended to the entire cortex, which is made up of around 1011 neurons. This channel should be pictured as an extremely thin, densely looped labyrinth, joining at a multi-directional level most of the cortical neurons.

Here are a few data, which we believe could support our view:

1) the glial cells' projections usually surrounding the synapses do not establish a physical contact on postsynaptic neurons: a very thin passage is left in which intercellular fluid can move and so we can presume that glial cells may extend the banks of the channel beyond the natural limits of the synapses;

2) even though most synapses undergo a process of degeneration, their concentration is kept at a more or less constant level owing to the phenomena of synaptic reclamation and synaptic sprouting, which synthesize new synaptic buttons;

3) it may be recalled how neighboring synapses are characteristic of all local circuits marked by dendro-dendritic connections, such as are found in many different locations along the central nervous system (olfactory bulb, retina, brain stem, thalamus and in the cerebral cortex itself);

4) in such local circuits it often happens that single synapses may harbor more than one synaptic button - all of them being very close to each other.

The structure whose existence we conjectured, the thin virtual channel made up of a series of synaptic junctions arranged in a line, could be referred to as USC - Unified Synaptic Channel (or SUC - Synaptic Unified Channel). We use the expression "virtual" since it could be viewed as an anatomical formation that emerges mainly on a functional basis (which will be discussed below); like a river-bed which is so called for the presence of the stream of water that flows, or is supposed to flow, along its length.

It is a well-known fact that synapses are 200 Å wide: such free space is filled with a slender lining composed of polysaccharides, glycoproteins and glycolipids. The intersynaptic fissure is crossed by neurotransmitters, among which the most common are GABA (gamma-amino-butirric acid), with an inhibitory role, and glutamate, with an excitatory role; their journey from the presynaptic to the postsynaptic membrane accounts for the transmission and regulation of the nervous impulse across the synaptic space. Once the mediator molecules - from 5,000 to 10,000 of them are released during the exocytosis of a single presynaptic vesicle - have bonded with the appropriate receptors present on the postsynaptic membrane, they are released in the synaptic fissure and are reabsorbed by the presynaptic and by the glial membranes through a mechanism of active transport.

Since not all mediator molecules, once they are released at the presynaptic membrane, manage to bind with the receptors present on the postsynaptic membrane and not all of them are reabsorbed by the presynaptic neuron after having bonded, we gather the impression that in each synaptic transmission event a group of molecules appears to float in the synaptic fissure without any apparent relevant task to perform. In our opinion they should be referred, rather than to the classic type of synaptic transmission so far examined, to the system of non-synaptic communication between neurons of the cerebral cortex which in recent years has focused the attention of many neurophysiologists. Such a system does not rely solely upon the action of known neurotransmitters, but also involves other types of hormone-like substances, and particularly two gaseous molecules, NO and CO. These molecules, toxic at higher concentrations, together with the above mentioned unbound chemical mediators, are seemingly able to enhance or reduce the efficiency of the classic, synaptic type of transmission, which therefore operates embedded in a pool of chemically active substances circulating in the synaptic space. Such molecules, if considered by themselves, cannot account for the transmission of any other impulse in any other synapse, due to the fact that they are no longer present in "quantic" concentration [2], [3].

Rather, the above mentioned molecules are looked upon by many authors as the effectors of miniature excitatory (inhibitory) postsynaptic potentials {E(I)PSP}, as the basic informative bricks keeping the postsynaptic membranes under a constant low-level of excitement/inhibition. They express in this way a fine mechanism of regulation of the postsynaptic potentials of single neurons. On a small scale they build up a limit that presynaptic potentials must overcome, in order to be transmitted on the other side of the synaptic junction; on a larger scale, they modulate the expression of the state of "health" of the synaptic routes, that is to say, they control the quality of the response to incoming impulses, whether they will be reinforced or weakened.

Some of the cerebral functions which make use of the modulation system we just briefly described, such as rage and aggressive reactions, are surely related to behavioral systems connected to the older regions of the brain (the paleocortex and relative basal ganglia). On the other hand, mechanisms which support most learning and memory processes can be related to the neocortex and to its principal characteristic: plasticity; these mechanisms as a matter of fact are being investigated for their modulative properties. Any proposed and possible model would have to cope with the issue of an extreme, inevitable complexity. How may the structure we called USC (SUC) help us in the definition of the plastic moulding of the associative areas on the different, precisely cabled, sensory neuronal networks? In our opinion, the mentioned multi-directional spatial development of the USC (SUC) could give the model the advantage of being at the same time intuitively simple and sufficiently complex. The model refers to the totality of the molecules present in each synaptic fissure at any given instant, that is to say, both the mediator and the modulating molecules, and follows their diffusion along the USC (SUC). In more detail: we saw that the molecules can bind to the appropriate receptors present on the postsynaptic membrane; that they can be reabsorbed by the presynaptic and glial membranes; or else they could stream, at a very slow pace if compared with the speed of synaptical impulse transmission, along the USC (SUC) and thus become connected with nearby, or even further away synapses, where they could get involved in the process of impulse regulation. According to this model the molecules would thus gain an additional informative value; for their presence in the synaptic fissures would become relevant apart from their bonding or reabsorption, since by the process of diffusion they would induce concentration changes in other portions of the cortex, thus affecting the underlying mosaic of neuronal activity and inhibition. The consequent process of spatial and temporal addition along the channel-like structure, viewed as being partly independent of the frequency of incoming impulses, and at the same time viewed as being at least partly in charge of the frequency of outgoing impulses, could account in our view for the complexity required by tentative explanations of the nature of consciousness.

The accepted models for the integration of all the different types of consciousness based on sensory (optical, auditory etc.) or "higher" information (the highly specialized centers of language - themselves probably associated with sensory-based memory) are all based on the theory of selective activation of different groups of neurons, mostly arranged in hierarchies. Such theory, in turn, relies upon the deeply rooted belief that all forms of consciousness - even self-consciousness - consist of varying degrees of perceptive consciousness. It cannot be denied that self-consciousness rests on sensory perception and in fact all hierarchical models which examine such processes of perception via neuronal activation are of invaluable help - it is enough to think of the powerful work that has thrown light on the optic system. We share the same belief, but we carry it one step further. Instead of postulating the need for the final stage of integration, where all sensory-based hierarchies build up the last level of selective neuronal activation - the level of all encompassing and all supervising consciousness, we believe that the process - or the result - of self-consciousness could be more clearly hinted at by considering how changing molecular concentrations, along a formation such as the USC (SUC), could determine a subtly regulated transmission of all incoming presynaptic impulses; thus giving rise to a low-level and simultaneous (non hierarchical) activation of all relevant neuronal networks. The emergence of the awareness of the self would thus appear to be based upon a mechanism of extremely small and shortly-lived (because they tend to be reabsorbed) parcels of neurotransmitters and other molecules, which according to their diffusion rate seem to sum up their effects to produce a constant flow of material, consciousness resulting as a whole. But, if so interpreted, the model does not give any clear advantage over the hierarchical model, and it even does not represent a true alternative, since it remains yet to be supported by some kind of experimental evidence. However, if we consider self-consciousness not as a single, constantly present event, we may discover that the model leads us to another possible interpretation. Since not all portions of the channel-like structure have in time the same level of response to the chemical mediators (the single postsynaptic membranes go through various stages of chemical activity/sensitivity), the unity we hinted at as the result of the flow of molecules may be so only in appearance; there should not be one flow, rather a mosaic of miniature flows; every step of their integration along the USC (SUC) should be separate from the following one; self-consciousness could be a mosaic of successive time-events, which only apparently become integrated into a whole. This occurrence seems to us to be hardly explicable on a purely hierarchically based model.




[1] F. Crick, The Astonishing Hypothesis (Macmillan Publ. Comp., NY, 1994).

[2] F. Beck, J.C. Eccles, Quantum aspects of brain activity and the role of consciousness, Proc. Nat. Acad. Sci. (1989), pp. 11357-11361.

[3] H.P. Stapp, Mind, Matter and Quantum Mechanics, (Springer, Berlin, 1993).