The wiring-in of neural nets revisited

Earlier and some recent ideas about the possible modes of specification of the wiring-in of nervous systems are reviewed in the light of older and several recent experiments, and some new ideas are suggested. It is argued that certain general principles, notably the postulated ‘principle of alternative matching’ (PALMA) and a suggested and related ‘kaleidoscopic effect’ (KALEF), as well as the notion of an ‘extracellular guidance network’ (ECGN), are in good agreement with recent and older findings concerning axonal guidance during neural wiring-in. It seems possible that by means of genetically programmed processes, neurons become systematically combinatorially labelled to such a degree that possibly all neurons areuniquely specified, as regards the combination oftypes of cell labels they make. Yet, there remains considerable freedom as regards the modes of arrangements of cell labels within cell surface membranes and the KALEF permits to overcome apparent difficulties that confronted earlier versions of the cell labelling hypotheses (cf. Edelman,Science 219, 450–457, 1983, for mention of such difficulties). Apart from label specification, neural development seems to depend on trophic factors, which are also essential for the maintenance of the developed nervous system. The systematic programmes for cell labelling, apart from generating all the required neurons, also produces inappropriate neurons and synaptic connections. These are got rid of by systematic cell death and/or atrophy of inappropriate synapses and/or elimination of inappropriate axon collaterals. The resulting neural net seems then very specifically wired-in for each species, apparently without redundant neurons.