Over the Rooftops of Time: Jewish Stories, Essays, Poems

The Knockout Mouse on the Doorstep of Neurobiology (or, the Mind/Body Problem Revisited)

The Knockout Mouse on the Doorstep of Neurobiology (or, the Mind/Body Problem Revisited) These days, neuroscience is beginning to resemble philosophy. The age-old questions about the nature and location of consciousness , the relationship of mind to body and self to physical world, are being asked once again, but this time in more concrete terms by neuroscientists. Our concept of the relation between ourselves and the physical world is thought by Leif Finkel through his work on visual perception and computer modeling to be a representation of an internal construct that we project upon the external world. In his words, “much of the consistency and logic of external events is then a property of the ‘perceiver’ rather than the perceived object. . . . What we take to be the basic physical properties of our environment, may reflect the structure of our brains more than the structure of the universe.”3 1 0 3 Perhaps Dante was considering the mind/body question with his emblematic use of Bertrand de Born—the troubadour who set father against son and walked the rim of the eighth circle of the Inferno carrying his severed head by the hair, swinging it like a lantern: “I bear my brain divided from its source within this trunk.” We might also remember Jonathan Swift’s interdigitation—the exchange of a half-brain of one leader with that of another to achieve a modicum of peace. Neither shed much light on the nature of reconciliation. However, both pointed to the possibility that the “human body and the human mind met inside the skull.” We leave behind Aristotle who set mind farther down, in the rag and bone shop of the heart. One most curious phenomenon on its way to being deciphered is exactly how developing neurons make connections with one another. Each nerve cell can form up to 10,000 such connections or synapses. Does the wiring plan call for a complete construction of all such connections ? Or is the brain so adaptive, so flexible that its architecture involves a basic framework with the rest of the constructive work left to brain function itself? As Dr. Carla Shatz, Chair, Department of Neurobiology, Harvard Medical School, describes it, “The wiring diagram of the adult brain is wonderfully complex and precise, as if nothing has been left to chance. How is this precision achieved during brain development? . . . It is not as easy as soldering together the connections of a computer.” Axons must recognize their correct targets and must bypass other areas, “just as [we] might drive past Philadelphia en route from New York to Washington.”4 Dr. Shatz tells us that “there are really two broad phases to brain wiring: an early phase that lays down basic brain circuits and does not require brain activity, and a later phase that refines circuits into their adult precision” through brain activity. An elegant illustration of this two-phase process occurs with the circuitry to do with language. The brain doesn’t know if its owner will speak English or Serbo-Croatian. Thus, the fundamental framework is laid down and is, in theory, applicable to all languages. The specifics of a particular language are not brought into play until after the birth of the child. Thus the exquisitely adaptive relation between self and environment. Understanding neuronal development may prove useful in the eventual treatment of neurological diseases and trauma. The ability to regenerate nerve cells is of considerable clinical importance. How can nerve cell growth and survival be facilitated? Nerve cells in culture have not 1 0 4 OVER THE ROOFTOPS OF TIME provided the answers. But a learned borrowing from a companion science , immunology, the use of so-called knockout mice (mice that have been genetically altered) has recently penetrated the field of neurobiology . Previous studies were done with the use of antibodies that interfered with nerve growth factors. But the application of the first animal model lacking one of the four known neurotrophin molecules (neurotrophins promote survival and differentiation of various nerve cell populations) has the potential of advancing our understanding of neuronal development and hence our ability to evaluate potential treatment for human neurological diseases. The ultimate goal is to understand how different neurotrophins interact during neural development to produce an intact embryo, and then learn to recreate these interactions to heal or rescue damaged nerve cells later in life. “It is understandable,” says Gustav Eckstein, “that...