Challenges to Body Fluid Homeostasis Recruit Mesolimbic Dopamine Signaling

The internal environment of a living organism must remain stable in order to ensure optimal performance and ultimately survival. The generation of motivated behaviors is an adaptive mechanism for defending against homeostatic disruptions. While physiological state has been shown to modulate motivated behaviors, the influence of physiological state on phasic dopamine signaling, an underlying neurobiological substrate of motivated behavior, is underexplored. This thesis uses perturbations of body fluid homeostasis to highlight the influence of physiological state on phasic dopamine release. Here, I hypothesize that nucleus accumbens dopamine signaling will be recruited in response to sodium or water only under conditions of physiological need (i.e. sodium or water deprivation, respectively). I use fast-scan cyclic voltammetry to measure subsecond changes in dopamine concentration in the nucleus accumbens shell of homeostatically balanced, sodium deplete, and water deprived rats. Increases in dopamine concentration are observed only under conditions of physiological deficit. Furthermore, the dopamine increases are taste selective and limited to those which satisfy the need state of the animal. Thus, dopamine neurons track fluid balance and respond to sodium and water stimuli in a state and taste-dependent manner. I next examine a potential circuit by which sodium need is communicated to mesolimbic circuitry. Using Fluorogold tracing and immunohistochemistry for c-Fos and Foxp2, a marker of sodium-deprivation responsive neurons, I highlight populations of cells in both the pre-LC and PBel-inner that are activated by sodium deprivation and project directly to the VTA. The two identified projections may modulate dopamine neuron excitability and consequently the state-specific dopamine release observed in my experiments. This work uses sodium appetite and thirst to illustrate the impact of physiological state on mesolimbic dopamine signaling and a potential circuit by which homeostatic disruptions are communicated to dopamine neurons. As mesolimbic signaling plays a key role in reinforcement processing, my findings support the possibility of using manipulations of physiology and its endogenous hormone systems to alter motivated behaviors- both adaptive and, importantly, maladaptive (i.e. drug abuse, obesity).