Magnetoencephalography (MEG) is a noninvasive technique for investigating neuronal activity in the living human brain. The time resolution of the method is better than 1 ms and the spatial discrimination is, under favorable circumstances, 2-3 mm for sources in the cerebral cortex. In MEG studies, the weak 10 fT-1 pT magnetic fields produced by electric currents flowing in neurons are measured with multichannel SQUID (superconducting quantum interference device) gradiometers. The sites in the cerebral cortex that are activated by a stimulus can be found from the detected magnetic-field distribution, provided that appropriate assumptions about the source render the solution of the inverse problem unique. Many interesting properties of the working human brain can be studied, including spontaneous activity and signal processing following external stimuli. For clinical purposes, determination of the locations of epileptic foci is of interest. The authors begin with a general introduction and a short discussion of the neural basis of MEG. The mathematical theory of the method is then explained in detail, followed by a thorough description of MEG instrumentation, data analysis, and practical construction of multi-SQUID devices. Finally, several MEG experiments performed in the authors' laboratory are described, covering studies of evoked responses and of spontaneous activity in both healthy and diseased brains. Many MEG studies by other groups are discussed briefly as well.

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Magnetoencephalography—theory, instrumentation, and applications to noninvasive studies of the working human brain

Conducting polymers in biomedical engineering

GAP-43: an intrinsic determinant of neuronal development and plasticity.

Elongation ofaxons and active remodeling of their terminal arbors under­ lies the assembly of neural circuits during development, determines the success or fai lure of nerve regeneration, and may contribute to some forms of synaptic plast icity in adult brains. For most neurons, elongation of a principal axon is confined to a few days or weeks during development. Remodeling of axon terminal arbors also is most pronounced during transient "critical periods" late in development, although some forms of synaptic remodeling continue throughout lif e (Lichtman et aI19 87). Once past these epochs of axon elongation and dynamic sorting of synaptic terminals, it might be possible to stabilize principal axon branches or their terminal arbors by inactivating some of the molecular processes required for growth and synaptogenesis. Selective inactivation or retention of some growth-related processes in maturing neurons might then define some limits on the mechanisms available for synaptic remodeling in the adult nervous system. Studies of axon regeneration in vivo and in tissue culture indicate that some aspects of axon growth are indeed repressed in many adult neurons but can be re-induced under some conditio ns. Although such studies have considered primarily the elongation of primary axons, they also raise the possibility that neuronal processes underlying more subtle aspects of axon growth and synaptogenesis may be down-regulated chronically in mature neurons. At the molecular level, periods of axon outgrowth during devel­ opment and re-induction of axon growth for regeneration are correlated with large and specific changes in synthesis of a few proteins transported into the growing axons. This suggests the hypothesis that

Axonal growth-associated proteins.

Nerve growth factor (NGF) is a trophic agent that promotes the outgrowth of nerve fibers from sympathetic and sensory ganglia. The neuronal differentiation stimulated by this hormone was examined in the NGF-responsive cell line PC12. Differential hybridization was used to screen a complementary DNA library constructed from PC12 cells treated with NGF and cycloheximide. One of the complementary DNA clones that was rapidly induced by NGF was found to have a nucleotide sequence that predicts a 54-kilodalton protein with homology to transcriptional regulatory proteins. This clone, NGFI-A, contains three tandemly repeated copies of the 28- to 30-amino acid "zinc finger" domain present in Xenopus laevis TFIIIA and other DNA-binding proteins. It also contains another highly conserved unit of eight amino acids that is repeated at least 11 times. The NGFI-A gene is expressed at relatively high levels in the brain, lung, and superior cervical ganglion of the adult rat.

https://science.sciencemag.org/content/sci/238/4828/797.full.pdf

A nerve growth factor-induced gene encodes a possible transcriptional regulatory factor

Growth cones are specialized structures that form the distal tips of growing axons. During both normal development of the nervous system and regeneration of injured nerves, growth cones are essential for elongation and guidance of growing axons. Developmental and regenerative axon growth is frequently accompanied by elevated synthesis of a protein designated GAP-43. GAP-43 has now been found to be a major component of growth-cone membranes in developing rat brains. Relative to total protein, GAP-43 is approximately 12 times as abundant in growth-cone membranes as in synaptic membranes from adult brains. Immunohistochemical localization of GAP-43 in frozen sections of developing brain indicates that the protein is specifically associated with neuropil areas containing growth cones and immature synaptic terminals. The results support the proposal that GAP-43 plays a role in axon growth.

http://science.sciencemag.org/content/sci/233/4765/783.full.pdf

A protein induced during nerve growth (GAP-43) is a major component of growth-cone membranes.

GAP-43 is one of a small subset of cellular proteins selectively transported by a neuron to its terminals. Its enrichment in growth cones and its increased levels in developing or regenerating neurons suggest that it has an important role in neurite growth. A complementary DNA (cDNA) that encodes rat GAP-43 has been isolated to study its structural characteristics and regulation. The predicted molecular size is 24 kilodaltons, although its migration in SDS-polyacrylamide gels is anomalously retarded. Expression of GAP-43 is limited to the nervous system, where its levels are highest during periods of neurite outgrowth. Nerve growth factor or adenosine 3',5'-monophosphate induction of neurites from PC12 cells is accompanied by increased GAP-43 expression. GAP-43 RNA is easily detectable, although at diminished levels, in the adult rat nervous system. This regulation of GAP-43 is concordant with a role in growth-related processes of the neuron, processes that may continue in the mature animal.

https://science.sciencemag.org/content/sci/236/4801/597.full.pdf

Cloning of complementary DNA for GAP-43, a neuronal growth-related protein

Alpha-bungarotoxin binding and central nervous system nicotinic acetylcholine receptors.

The magnetic field of the action potential from an isolated frog sciatic nerve was measured by a SQUID magnetometer with a novel room-temperature pickup coil. The 1.2 x 10(-10) tesla field was measured 1.3 millimeters from the nerve with a signal-to-noise ratio of 40 to 1.

http://science.sciencemag.org/content/sci/208/4439/53.full.pdf

Magnetic field of a nerve impulse: first measurements

alpha-Neurotoxins bind to cholinergic receptor, block transmission, and induce sprouting of retinal terminals in the toad tectum. New connections retain an orderliness that suggests a selective affinity between presynaptic terminals. The results suggest that postsynaptic cells exert a control, associated with receptors, on the growth of presynaptic terminals and on the maintenance of their synaptic connections.

John A. Freeman

Papers

A protein induced during nerve growth (GAP-43) is a major component of growth-cone membranes.

Cloning of complementary DNA for GAP-43, a neuronal growth-related protein

Alpha-bungarotoxin binding and central nervous system nicotinic acetylcholine receptors.

Magnetic field of a nerve impulse: first measurements

Possible regulatory function of acetylcholine receptor in maintenance of retinotectal synapses