4. Selforganization in the Brain

4.2 Development

Now we will try to find evidence for the hypothesis that selforganization plays a role in the development of the brain. At what level can we expect to find signs of this role? The prerequisites are a large number of similar, interacting neurons and positive feedback mechanisms. The cortex combines a high synapse density with a relatively homogeneous structure. Positive feedback (mutual inhibition and recurrent excitation) is to be expected due to the abundance of interneurons. Which type of structures must we look for? The examples given in Part 2 can provide us some clues. Most of them are characterized by a spatial periodicity in at least one dimension: mosaic patterns, rings, regular stripes. A number of different labeling techniques have demonstrated the presence of spatially periodic structures or activity patterns in the mammalian visual cortex:

1.  A few weeks after injection of 3H-proline in one eye, autoradiography of the visual cortex showed the presence of ocular dominance columns (Hubel, 1982), an extremely regular stripe-like pattern which is periodic in one dimension. The pattern corresponds to a regular alternation of projections of both eyes.

2.  Experiments using 14C-deoxyglucose to measure cerebral glucose utilization showed the existence of ocular dominance columns (DesRosiers et al., 1978) after occlusion of one eye, orientation columns (Hubel, Wiesel and Stryker, 1978) after stimulation of both eyes with stripes of only one orientation, and spatial frequency columns (Tootel, Silverman and DeValois,1981) after stimulation of both eyes with stripes of all orientations but only one spatial frequency. All these structures are spatially periodic 'activity patterns' which arise after special stimulation.

3.   Cytochrome-oxidase (CO) staining of primate visual cortex showed a 'regular patchy distribution' (Horton and Hubel, 1981; Hubel, 1982, Wong-Riley and Carrol, 1984) which is very similar to the static mosaic patterns found in the BZ-reaction. This periodic structure does not require any special visual stimulation.

4. Immunocytochemical localization of the GABA synthesizing enzyme GAD showed a columnar organization into patches, matching the cytochrome oxidase pattern (Hendrickson et al., 1981; Hunt, 1982)

5.   A monoclonal antibody against an uncharacterized antigen on the surface of certain neurons (CAT 301) demonstrated a regularly patchy distribution of these neurons (Hendry et al., 1984).

6.  After treatment of monkey striate cortex with voltage-sensitive dyes, spatially periodic activity patterns corresponding to orientation and ocular dominance columns, were seen (Blasdel and Salam, 1986).

7.   Periodic intrinsic connections have been demonstrated in the visual cortex of the tree shrew, by local injections of HRP (Rockland and Lund, 1982). These results are consistent with intra-cellular HRP injections in single neurons, showing a periodic arborization pattern (Gilbert and Wiesel, 1980; Wiesel, 1982).

 

All these periodic structures are interrelated in a complex way, while experience often has an effect on their development (reviews: Hubel, 1982; Wiesel, 1982; Swindale, 1982). Swindale (1981a) has explained the spontaneous formation of ocular dominance patterns out of an initially unsegregated uniform distribution of projections of both eyes, by a few simple competition rules.

          

Both 14C-deoxyglucose and cytochrome-oxidase staining, are methods for measuring metabolic activity which is coupled to electrical activity (Torbati et al., 1983; Sokoloff, 1977). Still, anatomical structures are thought to underlie these 'activity patterns'. The periodicity seen in orientation and frequency columns can be thought of as a direct consequence of the regularity of the visual stimuli necessary to produce them, but this relationship is not at all self-evident. Retinotopic mapping of these images in unconstrained animals during at least 30 minutes will probably produce a quite homogeneous average stimulation of the visual cortex. Therefore, the observed regularity of the activity patterns is not imposed by stimulation. The formation of these periodic activity patterns can be explained by selforganization. The following mechanism is proposed. Neurons in the visual cortex are tuned to various clues (orientation, size, contours, spatial frequency). Prolonged visual stimulation which is rich in one of these clues will produce an overall increase of excitation. Inhibitory interneurons, which are abundant in the cortex, will also become activated, and raise the level of inhibition. A simultaneous increase of excitation and inhibition is incompatible with a spatially homogeneous distribution of activity. As a consequence, the initially homogeneous distribution of activity can become unstable and a spatially periodic activity pattern may result, analogous to the formation of Benard cells and the static mosaic pattern in the BZ reaction. In such a spatially periodic activity structure both the excitatory and inhibitory neurons can be simultaneously activated.

          

The other patterns (CO, GAD, CAT 301) do not require special visual input, they reflect a periodic organization of the cortex, which is more directly demonstrated by the HRP experiments. The clear relationship of these periodic structures with energy metabolism and functional activity, together with their plasticity suggests the following hypothesis for their development and maintenance. In the initially homogeneous cortical layers, spatially periodic activity patterns develop due to the high level of energy dissipation by a selforganizing process as defined in Parts 2 and 3.  The developing mammalian cortex differs from the adult one in a number of aspects which could favor selforganization. Initially, the cortex is relatively "self-contained": sensory projections are not yet established and cortical activity is not disturbed by unpredictable external sensory input. Interaction between cells is relatively strong due to the low number of glial cells and the initial over-production of synapses. Due to the high level of plasticity in this early stage of development, activity patterns can be 'imprinted' in the wiring diagram. 'Hebbian' synapses (cf. Viana di Prisco, 1984) play an essential role here. The periodic intrinsic connections which result, promote organized activity structures, thus providing a positive feedback mechanism for their maintenance.  Although sensory input is a priori not a necessary prerequisite, it may in a later stage help to keep the level of activity (degree of energy dissipation) at a sufficiently high level. In this way, sensory input can have an important influence on the type of structures formed. In some cases (ocular dominance columns) deprivation of sensory input leads to the absence of structures normally formed (Swindale, 1981b).

      
Time-independent spatially periodic activity patterns were found by Kaczmarek and Babloyantz (1977), studying the behaviour of a neuronal network model. Although they failed to see the physiological significance of such solutions, these findings seem to be very relevant in the light of the present discussion. Ermentrout and Cowan (1979) showed the existence of stable spatially periodic activity patterns (both mosaic patterns and 'rolls') formed spontaneously out of an initially homogeneous situation, in a two-dimensional neural network model. Both studies show that selforganized spatial activity patterns can arise in neuronal networks, without making very special assumptions about connectivity and interactions.