The long-term objective is to determine the mechanism(s) by which cultured cells of the rat hippocampal formation (HF) control cholinergic function in rat sympathetic neurons from the superior cervical ganglion (SCG) and to find out whether HF cells, like cultured cardiac cells, also affect other transmitters in the large repertoire shared by sympathetic neurons and the HF. Evidence that postnatal HF cells, like cardiac cells, produce a """"""""cholinergic factor"""""""" (hereafter called the putative CF) when denervated by being placed in culture is potentially of interest in relation to dementias, in which central cholinergic function is impaired, and in design of transplantations intended to compensate for loss of central cholinergic function. These matters will be studied in co-microcultures of the two types of cells and whenever possible, in vivo. Microculture assays provide highly sensitive functional assays for all transmitters and factors, known or unknown, to which the cells are responsive.
The Specific Aims i nclude the following: 1) To investigate the action(s) and source(s) of the putative CF: by demonstrating plasticity via an adrenergic-to-cholinergic transition, by discovering if adult-derived SCG neurons are affected by the putative CF and if adult-derived HF cells exert the effect; by determining the cellular source(s) of the putative CF (glia alone? which parts of the HF? cells from other parts of the brain?). 2) To identify the putative CF: as a first step, is it similar antigenically, in action(s) or in purification protocol to several known factors that induce cholinergic function in SCG neurons? 3) To investigate the transmitter repertoire of SCG neurons in this format and to look for induced plasticities of this repertoire other than adrenergic-to-cholinergic. 4) To compare the transmitter repertoire of co-microcultured SCG neurons with the repertoire of SCG axons in vivo that sprout into the lesioned adult HF or that may sprout into the Alzheimer's HF. 5) To investigate substrate molecules involved in growth of SCG axons on HF cells in culture and in vivo.
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