The Blush II gAP

We tend to think of electrical activity as the primary function of neurons. Yet neurons have a complex physiology which goes well in excess of electrical activity alone. One of these physiological aspects is that some kinds of electrical activity, which by means currently ill-understood are judged as "novel", excite into motion transcriptional programs which ultimately result in long-term changes underlying memory. Let me belabor the point that as we effortlessly visually and auditorily parse scenes around us, we perceive distinct objects which we immediately recognize-and there is no re-cognition without a prior cognition and the memory of it. Even in the shortest of timeframes, the fractions of seconds required for a cognitive event, the path travelled by electrical activity in the brain does not propagate over virgin ground, but rather over a landscape that was labored by means of complex transcriptional patterns.

David Clayton has nicknamed the transcriptional programs triggered by various kinds of electrical activity the genomic action potential (gAP), in analogy with the more familiar electric action potential [35]; he describes the latter as integrating over the dendritic arbor inputs the various forms of electrical activity conveyed by synapses, while the former integrates in time, over a much longer timeframe, the changes and adaptations necessary to become memory. Clearly it is no less a neuronal function to adapt than it is to integrate and transmit information-even the dumbest being with neurons has a memory.

3.8 Meditation

Neuroscience is a highly charged, ideologic field. Where else would a choice of preposition denounce an ideological stance? When we were preparing our first manuscript on this subject, my collaborators and I got into a heated argument over the phrase: "the sensory environment is processed by the brain". The issue was whether to use "by the brain" as opposed to "in the brain"; in the first case, the brain is the active element which takes the initiative, goes out and finds the world and analyzes it; while in the second case, we have the brain as information processor, brain as computer, brain as Shannon communication channel idea.

The topoisomerase collaboration started when John Marko dropped down for a visit and related the problems in identifying a mechanism raised by the Rybenkov study; I have learned a lot from John in the 12 years we have done research together, and hope to continue. Most of the gene chip data analyis and algorithm development described here was carried out by Felix Naef, working on data of our excellent collaborators: Dan Lim and Arturo Alvarez-Buylla, whose work on neurogenesis in the adult mammalian brain started us trying to refine the analysis techniques available, and Nila Patil and Colleen Hacker at Perlegen (formerly the human genetics division of Affymetrix), first through the collaboration on neurogenesis and afterwards on the rheumathoid arthritis data; the Drosophila circadian rythm dataset by the Young lab, etc. The canary work was done in collaboration with Sidarta Ribeiro and Claudio Mello, then at the lab of Fernando Nottebohm, who has been extremely supportive of all of our nonsense; and on our side, most of the work was done by Guillermo Cecchi; I'd also like to acknowledge the work of Pabel Delgado, in charge of the "prosciutto machine". That work received invaluable ideological support from Roy Crist and the ineffable support of Jim Hudspeth. Finally, I would like to warmly thank the organizers of the Les Houches meeting, the colleagues who taught the other courses and lectures, and, particularly, the students at the Les Houches summer school, for an extremely stimulating time.


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