How neural circuits form and are modulated by local and long distance signaling is a fundamental problem in neuroscience. Astrocytes are glial cells that provide one critical source of local signaling that regulates synapse formation and circuit function in the central nervous system (CNS). Less is known, however, about peripheral satellite glia that are found at the junctions between spinal cord neurons and peripheral sympathetic neurons. The neurons of the sympathetic ganglia provide critical neural control of peripheral functions, modulating the final output of central sympathetic drive, regulating peripheral organ function, and providing ongoing information to the CNS. Disruptions in the sympathetic circuit contribute to many human disorders, including neurological diseases such as Parkinson?s disease and dementia. Within the sympathetic ganglia, satellite glia enwrap neuronal cell bodies and the cholinergic synapses that form between spinal cord inputs and postganglionic neurons, yet how these glial cells contribute to the formation and function of the sympathetic circuit remains to be determined. We have shown that cultured satellite glial cells isolated from the superior cervical ganglion (SCG) promote the development of structural synapses and synaptic activity of sympathetic neurons, indicating a potential role in setting circuit activity. In addition, satellite glial cell activity has been implicated in the acute regulation of sympathetic-mediated cardiovascular processes, suggesting that these glia could provide short-term and long-term regulation in this system. Here we will perturb the activity state of ganglionic satellite glia in vitro and in vivo to test the hypothesis that these glial cells regulate the development and output of the peripheral sympathetic circuit by coordinating presynaptic and postganglionic neuronal properties. We will examine the effects of glia on the intrinsic, synaptic and functional properties of postganglionic sympathetic neurons in the absence of their spinal cord presynaptic partners by selectively enhancing glial activity with the hM3Dq DREADD (Designer Receptors Exclusively Activated by Designer Drugs) in vitro. We will then use DREADD-expressing mice to investigate glial effects at synaptic sites originating from spinal cord inputs in vivo. These experiments will allow us to define the cellular mechanisms of glial actions and to determine their effects on the output of the sympathetic circuit.
Nerve cells in the brain and spinal cord control the functions of bodily organs such as the heart through the activity of peripheral sympathetic neurons that reside outside of the central nervous system. This project investigates how a class of peripheral non-neuronal cells, called satellite glia, regulate the development and function of the junctions that link the central and peripheral sympathetic systems. This work will lead to an understanding of how the nervous system controls peripheral function in healthy individuals and provide information on how these processes may be disrupted in disease.
