1. Introduction
The number of neurons in the mature brain is enormous, as is the problem of
understanding their functioning and development. To arrive at the very
organized and complicated structure of the full-grown brain, mechanisms
other than random formation of connections are needed. Many connections seem
to be predetermined in the way that they always turn out to connect specific
parts of the brain. This predetermination points in the direction of a
genetic mechanism controlling the formation of connections. However, in what
way this genetic control leads to the formation of specific connections is
still a matter of experimental exploration. Changeux and Danchin (1976)
pointed out that the information content of the DNA is far too limited to
account for all the connections to be specified. They state:
"The
DNA(...) may, at most code for a few million proteins. (...), moreover a
significant proportion of it (more than 60 %)(a) does not correspond to genuine
genes".
The number of synapses in the central nervous system of a high vertebrate is
estimated
as
1014
(Barnes,1986).
In
addition,
the
relative
strengths
of
these
connections
(the synaptic efficacies) must be
specified. When comparing the number of genes with the number of connections
to be made during development, the influence of genetic mechanisms on the
fate of an individual connection seems negligible. One could argue that also
combinations of genes can be responsible for specific connections. In this
way, more connections can be specified with the same limited number of
genes. Such a mechanism has already been demonstrated for the genetic
control of the immune system. Here, a few hundred genes are shuffled and
recombined to make billions of different antibodies (Leder, 1982).
Furthermore, evidence is accumulating that 'gene shuffling' mechanisms are
operating outside the immune system, while cell recognition during embryonic
development has been put forward as a possible candidate. Therefore, the
argument that the information content of the DNA is too limited to account
for all the connections to be specified is not as self-evident as it
seems.
Whether or not it is possible in principle that every individual connection is genetically specified, such a strong predetermination is very unlikely in view of the adaptive and learning capabilities of the brain. Genetic control probably plays a major role in connecting the nervous system with the periphery (the muscles and sensory organs). The connections in the spinal cord and brainstem regions probably also are predetermined to a great extent, because the functions of these brain parts are not very susceptible to adaptive changes. In contrast, the higher brain regions, in particular the cortical areas, have been demonstrated to undergo plastic changes during life and their development has been shown to be sensitive to environmental conditions (Wiesel, 1982). This neuronal plasticity is not confined to the biochemical level (changes in synaptic efficacies), but also has anatomical consequences. Therefore, a stringent genetic specification of the connections is very unlikely in these regions. Other, less rigid, mechanisms can come into play.
Development of the brain never really comes to a standstill, but smoothly changes into the phenomenon of 'plasticity', which is strongly coupled to the functioning of the brain. General mechanisms relating development, plasticity and function may therefore deepen our insight into the functioning of the brain. Understanding higher brain functions is one of the major challenges of current research. The function of sleep patterns, the mechanism of memory and learning, the associative capabilities and sensory processing are phenomena which we are only beginning to understand. In spite of tremendous experimental effort to find the cause(s) of epilepsy, there is still no satisfying explanation for the sudden and unpredictable interruptions of normal brain function which characterize this disease.
A class of non-genetic mechanisms which could play a role in the development, functioning, plasticity and pathology of the brain is comprised by the term 'selforganization'(b). By selforganization is meant a spontaneous (physico-chemical) process by which an organized spatio-temporal structure develops in a system out of an initially non-organized state. The order which is arrived at is intrinsic: it is not forced upon the system by the environment. Moreover, it is stable: the effects of small perturbations (either spontaneous internal fluctuations or external disruptions) eventually die out. The phenomenon of selforganization was first described for physical and chemical systems and a thermodynamic theory explaining the onset of selforganization was developed. At the same time, exciting developments took place in branches of mathematics and physics dealing with nonlinear dynamical systems: 'strange attractors', 'deterministic chaos', 'catastrophes' are a few terms used to describe the bewildering variety of complex behaviours displayed by a majority of these systems.
In Part 2 some examples of selforganizing physical and chemical systems will be
given together with the general mechanism. Part 3 sketches the developments
in mathematics relating to selforganization. In Part 4 the use of this term
in the context of brain function and development will be investigated and a
possible role of selforganization in the brain is
discussed.
(a) The amount of non-coding DNA in humans is currently estimated at 98%. How much of this non-coding DNA has a biological function is under intense debate.
(b) The term 'selforganization' has aquired different meanings since 1988, many of them outside the realms of physics, chemistry and mathematics.