Homeostatic plasticity represents a set of mechanisms that is thought to ensure that neural spiking levels and/or synaptic strength are maintained within a physiologically operational window. When neural activity or neurotransmission is chronically altered for days in cultured neurons or some developing networks, changes in synaptic strength and cellular excitability are expressed that appear to compensate for the perturbation. The autonomic nervous system homeostatically controls many different bodily functions, such as blood pressure and temperature. However, following neural injury or in disease states (e.g. hypertension) these functions are maintained at levels outside the normal range, and this is often associated with chronically altered sympathetic drive. These observations have led us to ask if chronic changes in sympathetic drive could trigger homeostatic mechanisms that are either unable to recover the original activity levels or actually contribute to the inappropriate levels of sympathetic activity? In this application we are taking advantage of the expertise of the Wenner and Hochman labs to address this question (Wenner - homeostatic plasticity in developing systems, Hochman - sympathetic nervous system and an ex vivo sympathetic preparation). We are proposing to chronically inhibit sympathetic drive in the living adult mouse and then examine an ex vivo sympathetic preparation following treatment to identify homeostatic mechanisms that are expressed. We will carry this ex vivo analysis out in a preparation that captures the peripheral arm of the sympathetic circuitry, which also includes the target organ regulating vasomotor function (blood vessels). We will do this in both the adult and at earlier developmental stages when the sympathetic circuitry is maturing and when homeostatic plasticity mechanisms are typically observed. The results will provide a better understanding of conditions that produce chronic sympathetic dysfunction and will be important in designing strategies to correct these autonomic dysfunctions.
Several disorders are associated with chronically altered sympathetic nervous system activity. In this application we are proposing to study compensatory changes that are triggered by altered sympathetic output.
