During development, neurons make a number of important decisions and the normal function of the mature organism depends upon the correctness of these decisions. One such decision is which neurotransmitter(s) to use. The developmental mechanisms which control this choice and allow for correct matching of transmitter and target are poorly understood in the periphery and undefined in the central nervous system. The cholinergic sympathetic neurons that innervate sweat glands undergo a transition from adrenergic to cholinergic function during normal development in the intact animal similar to that previously described in sympathetic neurons developing in culture when exposed to a soluble factor released from heart cells. We propose to obtain direct evidence for a transition in transmitter phenotype using immunocytochemical techniques and to determine whether other cholinergic sympathetic and cranial parasympathetic neurons undergo such a change during normal development. Using in vitro and in vivo manipulations, we will determine whether the change in neurotransmitter phenotype documented for the sweat gland innervation is induced by their target and will determine the effect of the change of the expression of transmitter receptors on the target cells. Finally, we will examine early embryonic sympathetic ganglia to determine whether small intensely fluorescent or SIF cells are the common multipotential precursor for the sympathoadrenal lineage including adrenergic and cholinergic sympathetic neurons, mature SIF cells and adrenal medullary cells. The long-term goal of these studies is to understand the normal developmental decisions and the mechanisms that underlie them that shape the formation of functionally appropriate synapses in the nervous system.
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