Plasticity in preganglionic and postganglionic neurons of the sympathetic nervous system during embryonic development.

Sympathetic preganglionic neurons (SPNs) are the final output neurons from the central arm of the autonomic nervous system. Therefore, SPNs represent a crucial component of the sympathetic nervous system for integrating several inputs before driving the post-ganglionic neurons (PGNs) in the periphery to control end organ function. The mechanisms which establish and regulate baseline sympathetic tone and overall excitability of SPNs and PGNs are poorly understood. The SPNs are also known as the autonomic motoneurons (MNs) as they arise from the same progenitor line as somatic MNs that innervate skeletal muscles. Previously our group has identified a rich repertoire of homeostatic plasticity (HP) mechanisms in somatic MNs of the embryonic chick following in vivo synaptic blockade. Here using the same model system, we examined whether SPNs exhibit similar homeostatic capabilities to that of somatic MNs. Indeed, we found that after 2-day reduction of excitatory synaptic input, SPNs showed a significant increase in intracellular chloride levels, the mechanism underlying GABAergic synaptic scaling in this system. This form of HP could therefore play a role in the early establishment of a setpoint of excitability in this part of the sympathetic nervous system. Next, we asked whether homeostatic mechanisms are expressed in the synaptic targets of SPNs, the PGNs. In this case we blocked synaptic input to PGNs in vivo (48-hour treatment), or acutely ex vivo , however neither treatment induced homeostatic adjustments in PGN excitability. We discuss differences in the homeostatic capacity between the central and peripheral component of the sympathetic nervous system. Significance Statement The autonomic nervous system plays a critical role in the survival and health of an organism and therefore must be tightly regulated, as diseases involving autonomic dysregulation, such as hypertension, have dramatic health consequences. Evidence suggests that challenges to autonomic signaling during prenatal and neonatal periods can affect long term health. This early developmental critical period when the circuit is first establishing excitability levels is likely to depend on different plasticity mechanisms. It is unknown whether homeostatic plasticity, thought to be critical for the maturation of cellular excitability, is expressed in the developing autonomic nervous system. Here, we are testing the hypothesis that mechanisms of homeostatic plasticity are expressed in pre- and post-ganglionic neurons of the embryonic sympathetic nervous system.