The control of the sympathetic nervous system is achieved at a number of levels in the central nervous system to enable rapid and precise changes in sympathetic outflow to various organs and thus maintain homeostasis. We are investigating the spinal cord circuitry regulating the activity of sympathetic preganglionic neurons (SPNs), which provide the singular gateway between the CNS and the peripheral nervous system in sympathetic control. Using a combination of electrophysiology, immunohistochemistry and electron microscopy, we have identified novel groups of local presympathetic interneurons, investigating how they may fit into circuits involved in sympathetic control. We also examine how specific gap junctions contribute to rhythmic sympathetic activity, using a number of approaches and connexin knockout mice. Our data reveal extensive interneuronal interactions within the spinal cord that extend beyond the autonomic networks to the motor outflow and may thus serve to synchronize the two systems where appropriate. Interneurones are heavily innervated by serotonergic inputs and activation of serotonergic receptors induces rhythmic activity in reduced spinal cord preparations that involves both SPNs and interneurons. Gap junctions contribute to this activity and may play a critical role in synchronizing SPNs and autonomic reflex responses. GABAergic control of sympathetic outflow is achieved through activation of both pre- and postsynaptic receptors on interneurons and SPNs. These data indicate complex levels of spinal control of sympathetic outflow. As we unravel the circuits involved in influencing sympathetic activity, we gain insight into ways in which precise control of specific pathways may be achieved.

Supported by the British Heart Foundation and the Wellcome Trust.