The long range goal of this project is to identify factors which contribute to the ingestion of sodium or NaCl in excess of physiological need. The determinants of salt preference are of particular interest because high salt intake has been implicated in the development and maintenance of essential hypertension in humans. In the rat NaCl preference varies as a function of age and genetic characteristics, and these variations are associated with differences in signaling in gustatory pathways, in particular, amiloride-sensitive sodium signals conveyed by the chorda tympani nerve. Neonatal rats, of a variety of strains, prefer and freely ingest solutions containing remarkably high concentrations of NaCl, and their gustatory neural sensitivity to NaCl is relatively low. In contrast, the Fisher 344 (F344) rat fails to prefer NaCl solutions to water and avoids them at concentrations preferred by other strains. F344 rats show an amplified neural response to NaCl stimulation and this elevation appears to be due entirely to greater amiloride sensitivity. When the pathway carrying these signals is transected, the aversion disappears and F344 rats display a clear preference for NaCl. In addition, the recent finding of an anomalous preference for NH4Cl in adult rats which received CTX as neonates is reminiscent of the paradoxical NH4Cl preference of neonates, demonstrating the striking plasticity of the developing gustatory system as well as the involvement of multiple interacting pathways. Thus the studies in this proposal focus on determining the nature of these interactions and their potential for modification using these genetic and developmental variants as model systems. Studies will determine the effect on the microstructure of licking for NaCl of: strain; need state; nerve transection; and treatments which increase and decrease amiloride-sensitive sodium transport in taste buds. Studies of adult rats which received transections as neonates will determine whether their anomalous preference for NH4Cl is associated with an impaired ability to discriminate NH4Cl from NaCl. Neuroanatomical studies of early transected rats will examine terminal field organization of gustatory pathways in the nucleus of the solitary tract to determine whether altered preference stems from alterations in terminal fields of remaining gustatory nerves. Additional studies will define the relationship between maturation of gustatory pathways and developmental changes in taste preference using an assessment technique, taste reactivity, which can be applied with common methods across a wide range of ages.
