NEUROBIOLOGIC STUDIES OF NEURONS AND GLIA IN CELL CULTURE

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a) A tissue culture chamber system allows independent electrical activation of each of two sets of cholinergic axons innervating a common population of skeletal muscle cells. Axonal activation produces a loss of synaptic inputs to the muscle as in the case during development in vivo. We have shown previously that the serine protease thrombin plays a critical role in this process of activity dependent synapse reduction or ADSR. We now show that activation of the thrombin receptor by a thrombin receptor activating peptide (TRAP) can produce synapse loss. An analysis of a TRAP analogue, which in other systems is inactive, also fails to produce synapse loss. TRAP action involves activation of a protein kinase and we find that staurosporine, a protein kinase blocker, blocks both TRAP elicited and electrically induced synapse loss. b) Theoretical models of neural networks have suggested that spontaneously active "pacemaker" neurons could be important determinants of network behavior. We have found (using both calcium imaging and patch electrode recordings) that in cultures in which all excitatory synaptic activity is blocked, some 10% or so of neurons exhibit "pacemaker" activity. c) Time lapse microscopy has defined three types of axonal responses to target cells and three categories of guidance molecules are postulated which are differentially distributed amongst tectal (chick) and superior colliculus (mouse) target cells. Neurons in both phyla have repellent cues localized in one particular target region, whereas glia from chick and mouse appear to express qualitatively different classes of guidance cues.