Sunday, July 15, 2007

Steven Rose, Future of the Brain, excerpts

I love his action verbs - he uses them in such a way that it creates a clear mental movie to watch. From p. 72:
Young neurons must recognize their migratory path and move along it; finally they must at some point recognize when to stop migrating and instead begin to aggregate with other neurons of the same kind, put out axons and dendrites, and make the right synaptic connections... As the glia migrate they spin out long tails up which the neurons can in due course climb. The cell membranes of both neurons and glia contain a particular class of proteins called CAMs (cell adhesion molecules). In the developing tissue the CAM work a bit like crampons; they stick out from the surface of the membrane and cling to the matching CAM on a nearby cell; thus the neurons can clutch the glia and ratchet themselves along. As a further trick the migrating cells also lay down a sort of slime trail of molecules related to the CAMs - substrate adhesion molecules or SAMs - which provide additional guidance for the cells following. The neurons can move along the SAM trail rather like amoeba - that is, they ooze.

This part is reminiscent of Into the Cool, "Nature abhors a gradient" :
What provides such map-references for the cellular route-marches? Even if neurons follow glia, the glia themselves must have a sense of direction. Both distant and local signals must be involved. One way of signalling direction is to have already in place some target cell or tissue towards which the migration must be directed. Suppose the target is constantly secreting a signaling molecule, which then diffuses away from it. This will create a concentration gradient, highest at the target and progressively weaker at increasing distances from it, just as in the case of the unicells discussed in the last chapter... early born neurons secret a protein called reelin which sticks to the molecular matrix surrounding them, acting as a stop signal for each wave of arriving cortical neurons, telling them to get off the glial fibre and develop into a layer of mature neurons.

He uses principles established from other orders of magnitude to illustrate more about brain development, e.g., survival of, if not the fittest in a reproductive sense, survival of the fittest in terms of those most adept at connecting:
..there is a further process operating here. During embryonic development there is a vast overproduction of cells. Many more neurons are born than subsequently survive. More axons arrive at their destination than there are target cells to receive them. They must therefore compete for targets. Those that do not find them wither away and die. There is this in this model of development, competition for scarce resource - trophic factor, target cell, synaptic space.

He goes on to be more explicit:
This overproduction of neurons and synapses might seem wasteful. It has led to the argument that just as during evolution 'natural selection' will eliminate less-fit organisms, so some similar process of selection occurs within the developing brain - a process that the immunologist and theorist of human consciousness Gerald Edelman has called 'neural Darwinism'. However, this transference of the 'survival of the fittest' metaphor from organisms to cells is only partially correct. It seems probable that the whole process of cellular migration over large distances, the creation of long-range order, requires the working out of some internal programs of both individual cells and the collectivity of cells acting in concert. Even though synapses from only a particular neuron may end up making successful connections with its target cell, if the others had not been present during the long period of growth and migration it is doubtful whether a single nerve axon would have been able to reach the target. Survival of one depends on the presence of the many. Overproduction and subsequent pruning of neurons and synapses may at one level look like competition and selection; viewed on the larger scale, they appear as co-operative processes. It seems to be necessary, to ensure that enough cells arrive at their destination and make the relevant connections, that others must assist them, only themselves to die en route - a process called programmed cell death or apoptosis. Indeed, in a creature like C. elegans, ... those neurons destined to be born and to die en route to their seemingly final destination can be identified from the start. The process is orderly rather than random.

Here is something that is dear to me, because I thought of it independently - the idea of environments within and not just without. This makes total sense to me who sees the body as an ecosystem, kaleidoscopically, from multiple viewpoints, from the viewpoint of every cell (p. 59):
'The environment' is as much a myth as is 'the gene'. Environments exist at multiple levels. Thus for an individual piece of DNA 'the environment' is all the rest of the DNA in the genome, plus the cellular metabolic system that surrounds it, proteins, enzymes, ions, water ... For a cell in a multicellular organism... the environment, constant or not, is the internal milieu in which it is embedded or adjacent cells, signalling molecules, bloodstream and extracellular fluids. For organisms, the environment is constituted by the biological and physical world in which they move...

This supports the idea that the environment of nerves is just as important to them as the environment around anyone is to anyone.

There are more delicious bits in this book, but what I most appreciate so far about Rose is how he sees the human organism and all subparts of it and all functions of them as verbs, not nouns.

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