Age-related decrease of the chorda tympani nerve terminal field in the nucleus of the solitary tract is prevented by dietary sodium restriction during development.

Institution of a low-NaCl diet beginning at embryonic day 3 and continued throughout pre- and postnatal development has widespread effects on the neuroanatomical organization of the first gustatory relay in the nucleus of the solitary tract. To determine when these effects are expressed postnatally, the terminal field of the chorda tympani nerve was compared between sodium-restricted and sodium-replete rats at postnatal days 15-17, postnatal days 25-27, postnatal days 35-37, and adults. Total terminal fields were significantly larger in postnatal days 35-37 and adult sodium-restricted rats compared with aged-matched controls. The group-related differences appear related more to a remodeling of the terminal field in the dorsal zone of the terminal field in controls. Specifically, the terminal field volume in the dorsal zone in controls decreased dramatically from postnatal days 25-27 to postnatal days 35-37 and then again from postnatal days 35-37 to adulthood. In contrast, the fields did not change during development in sodium-restricted rats. These findings suggest that remodeling of the chorda tympani field occurs in controls at about the developmental period of taste response maturation. The lack of remodeling in sodium-restricted rats may be explained by a corresponding lack of functional response development to sodium salts. These results also illustrate the specificity and extent of how early dietary manipulations shape the developing brainstem.

Neuronal cell death and population dynamics in the developing rat geniculate ganglion.

In contrast to many neuronal systems, the pattern of developmental neuronal degeneration in the rat geniculate ganglion has remained undefined. To address this issue sectioned geniculate ganglia from embryonic day 13 to postnatal day 3 have been examined using standard histological techniques, TdT-mediated dUTP-digoxigenin nick end labeling to verify apoptotic activity, bromo-deoxyuridine incorporation to monitor neuronal precursor proliferation, and anti-beta-neurotubulin III to verify the neuronal identity of pycnotic cells. Results summed from alternate (embryonic day 13) or every third (embryonic day 14-postnatal day 3) section show that neuronal degeneration occurs as early as embryonic day 13 (6.8% of neurons counted), well before geniculate innervation of lingual taste buds at embryonic day 16. A degenerative peak occurs at embryonic day 17 (9.5%) followed by a decline (1.7% at embryonic day 18) and leveling off (0.1%-0.2% at embryonic day 22-postnatal day 3). Thus, geniculate neuronal degenerative pattern includes both innervation-associated histogenetic and morphogenetic cell death. Corresponding counts of mean neuronal numbers in the sections showed a continual rise from embryonic day 13 through embryonic day 18 (approx. 330-760) followed by a slight decline at embryonic day 19 (to approx. 630) and then a final leveling off at 800-825 by embryonic day 20. This pattern differs from many other developing neural systems which show a major population crash during initial target contact. It likely reflects different but slightly overlapping neuronal precursor proliferation and degeneration patterns in multiple geniculate neuronal subpopulations.

Lack of functional and morphological susceptibility of the greater superficial petrosal nerve to developmental dietary sodium restriction.

Restriction of dietary sodium during gestation has major effects on taste function and anatomy in the offspring. The chorda tympani nerve of offspring that are maintained on sodium-reduced chow throughout life (NaDep) has reduced neurophysiological responses to sodium and altered morphology of its terminal field in the nucleus of the solitary tract. There are many anatomical and physiological similarities between the chorda tympani nerve that innervates taste buds on the anterior tongue and the greater superficial petrosal nerve (GSP) that innervates taste buds on the palate. To determine if the GSP is similarly susceptible to the effects of dietary sodium restriction, the present study examined neurophysiological responses and the terminal field of the GSP in NaDep and control rats. Neurophysiological responses of the GSP to a variety of sodium and non-sodium stimuli did not differ between NaDep and control rats. Furthermore, the volume and shape of the GSP terminal field in the nucleus of the solitary tract did not differ between the groups. Therefore, despite the high degree of functional and anatomical correspondence between the chorda tympani nerve and the GSP, the GSP does not appear to be susceptible to the effects of lifelong dietary sodium restriction.

Neonatal chorda tympani transection permanently disrupts fungiform taste bud and papilla structure in the rat.

The present report examined the morphology of fungiform papillae in adult rats that received bilateral chorda tympani transection at 10 days of age. Tongue tissue was examined using surface-structure analysis. Counts were made of fungiform papillae with a pore, fungiform papillae with no pore and fungiform papillae with a keratinized conical surface; a feature referred to as "filiform-like. " Neonatal chorda tympani nerve transection resulted not only in a loss of taste buds but also in a permanent loss in numbers of fungiform papillae. Compared with an average of 152 fungiform papillae in sham-operated control rats, there was an average of only 54 fungiform papillae after neonatal chorda tympani transection. Nearly 80% of these fungiform papillae in neonatal chorda tympani transected rats were filiform-like. No filiform-like papillae were noted in sham-operated rats. These results suggest that the chorda tympani nerve is necessary during an early postnatal period of development to maintain normal fungiform papillae morphology.

Taste responses in the greater superficial petrosal nerve: substantial sodium salt and amiloride sensitivities demonstrated in two rat strains.

A great quantity of research has focused on neural responses of the chorda tympani nerve (CT) to taste stimuli. This report examined salt and sugar sensitivity of the greater superficial petrosal nerve (GSP) and the effect of amiloride on these neural responses. In addition to Sprague-Dawley (SD) rats that have CT responses typical of most rat strains, we included Fischer 344 (F344) rats whose CT responses to sodium chloride (NaCl) are higher than those of other strains. After a stimulation series in which water served as the rinse, a series of stimuli was presented in 100 microM amiloride. The GSP was highly responsive to NaCl, sodium acetate (NaAc), ammonium chloride, and sucrose; NaCl and NaAc responses were strongly suppressed by amiloride. Relative responses to NaCl were significantly higher in F344 than in SD rats. In summary, the GSP is highly sensitive to salt and sugar stimulation, and palatal taste receptors have a considerable degree of amiloride sensitivity.

Sodium appetite in the sham-drinking rat after chorda tympani nerve transection.

Sodium depletion in the neurologically intact rat (Intact) produces a prompt and robust intake of NaCl. After chorda tympani nerve transection (CTX), there is a longer latency and a reduced intake of NaCl. The CTX rat depends on remaining gustatory and postingestive information to direct NaCl intake. In the present study, the effect of the removal of the postingestive signals of ingested NaCl (by means of a chronic gastric fistula) on the NaCl intakes and licking patterns of Intact and CTX rats was studied. When the gastric fistula was open (Sham), ingested NaCl did not pass beyond the stomach, thus negative postingestive stimulation was absent. After overnight sodium depletion, when postingestive stimulation was present (i.e., gastric fistula closed; Real), the CTX group drank significantly less 0.3 M NaCl than the Intact group over the 2-h test [11.7 +/- 1.6 (CTX) vs. 15.3 +/- 2.8 (Intact) ml]. In contrast, when postingestive signals were absent (i.e., Sham) the Intact group ingested 52.5 +/- 4.4 ml, whereas the CTX group had ingested only 12.4 +/- 3.1 ml of 0.3 M NaCl. Lickometer data analysis revealed that even during the first minute of the test the CTX/Real group generated significantly fewer licks than any of the other groups. Thus, although the CTX group was sensitive to inhibitory postingestive signals in the early portion of the appetite test, the absence of these signals did not release the robust and sustained intake of NaCl characteristic of the Intact group. These results suggest that information provided by the chorda tympani nerve is critically important to the strong motivational properties of NaCl after sodium depletion.

Retention of conditioned taste aversion to NaCl after chorda tympani transection in Fischer 344 and Wistar rats.

Fischer 344 (F344) rats fail to prefer sodium chloride (NaCl) solution to water, and this behavior is dramatically altered by bilateral transection of the chorda tympani nerve (CTX). Tests of retention and generalization of a conditioned taste aversion (CTA) to 0.15 M NaCl were used to assess alterations in salt taste perception after CTX. A CTA was established to 0.15 M NaCl in groups of F344 and Wistar rats after two pairings with LiCl (IP, 2% body weight; 0.15 M). After conditioning, animals received bilateral CTX or sham operations. Approximately 2 weeks after surgery animals were tested for retention of the CTA. Aversion to 0.15 M NaCl was evident in CTX and SHAM rats that had been conditioned prior to surgery, with no apparent difference in magnitude as a function of surgical condition. Thus, although CTX profoundly alters F344 rats' hedonic response to NaCl, it does not alter perceptual characteristics so markedly that NaCl is no longer recognized as the stimulus presented during aversion conditioning. Rather these studies suggest that in both the F344 and Wistar strains the chorda tympani nerve is not necessary for retention of a presurgical CTA to NaCl. These studies, therefore, do not provide evidence of changes in NaCl perceptual "quality" as a consequence of CTX either in F344 rats, where such changes were indicated by the preference data, or in the Wistar rat, where they were not.

Neonatal chorda tympani transection alters adult preference for ammonium chloride in the rat.

The immature gustatory system of the neonatal rat is characterized by sensitivity to disruption by early interventions such as receptor or nerve damage. The present studies examined the effect of chorda tympani transection (neoCTX) of neonates on adult preference for salt and nonsalt stimuli. NeoCTX at 10 days of age led to a striking change in adult rats' preference for NH4Cl solutions but little change in preference for other solutions, including NaCl and KCl. Permanent anatomical effects of neoCTX included failure of the nerve to regenerate and a loss of all fungiform taste buds. Preference for NH4Cl was not due to an inability to discriminate it from NaCl. Following taste aversion conditioning to NaCl, neoCTX rats clearly distinguished between NaCl and NH4Cl. The effects on NH4Cl preference reflect a sensitive period during development because adult rats receiving similar surgery did not show any change in NH4Cl preference.

The CS-US interval and taste aversion learning: a brief look.

Temporal parameters of taste aversion learning are known to differ markedly from other learning paradigms in that acquisition occurs despite lengthy delays between exposure to conditioned (CS) and unconditioned stimulus (US). Far less consideration has been paid to very brief CS-US intervals and the possibility that this learning may also be distinguished by an ineffectiveness of close temporal contiguity between CS and US. The effectiveness of a very brief CS-US interval (10 s) was compared with that of 2 lengthier intervals (15 and 30 min). Temporal control of CS delivery (0.15% saccharin solution) into the oral cavity and US delivery (7.5 mg/kg apomorphine hydrochloride) into circulation involved infusion pumps and indwelling catheters. Using a 1-trial learning paradigm, CS-US delays of 15 and 30 min led to significant aversions whereas the 10-s CS-US interval did not, suggesting that close temporal contiguity between CS and US is neither necessary nor sufficient for conditioned taste aversion acquisition.

Participation in transvaginal ovarian cancer screening: compliance, correlation factors, and costs.

The objective was to identify factors influencing participation in screening for ovarian cancer using transvaginal sonography in the free experimental program at the University of Kentucky over its 6+ year history. Database records for screenings, performed from 1987 to June 1994, were utilized. Computer sorts, 1990 census information as predictors, and stepwise multiple regression analysis were employed. Participation in the model ovarian screening program took 3-4 years to approach > 300 screens/month, with repeat screenings exceeding new subject participation in this time period. A number of participants traveled > 200 miles for screening on both initial and repeat encounters. Analysis of distance to the screening site, median family income, county physician population, and education levels indicated that distance and then education correlated best with participation. Unit screening cost shrank from $45 to under $25 when maximal participation was achieved. Distance and education correlated with participation. Expenses compare favorably with diagnostic procedures for other diseases.

Amiloride sensitivity in the neonatal rat.

Amiloride-sensitive sodium channels in taste buds appear to play a key role in the response to NaCl stimulation, at least in adult rats. The researchers examined whether neonatal rats, which display an exaggerated preference for hypertonic NaCl solutions, lack functional amiloride-sensitive sodium channels. NaCl intake was significantly reduced by amiloride pretreatment, but water and ammonium chloride, NH4Cl, were unaffected. The researchers assessed whether the early appearance of amiloride sensitivity was mediated by effects on chorda tympani (CT) activity by sectioning the CT before testing. CT transection reduced intake of NaCl solutions and eliminated evidence of amiloride sensitivity. Amiloride sensitivity was also assessed by recording of whole-nerve CT activity at 8-11 days of age; the response to NaCl stimulation was significantly suppressed by amiloride. These data indicate that amiloride-sensitive sodium channels develop earlier than previously believed.

Gustatory deafferentation and desalivation: effects on NaCl preference of Fischer 344 rats.

The chorda tympani nerve (CT) appears to be particularly responsive to NaCl stimulation of the tongue. However, in most strains of rat, bilateral transection of the CT (CTX) results in little alteration of salt preference. The Fischer 344 (F344) strain of rat is unusual in its lack of preference for any concentration of salt. We recently reported a dramatic change from aversion to preference for salt in F344 rats after CTX. The present studies further explored this alteration in salt preference of F344 rats with an expanded range of NaCl concentrations. Additionally, the specificity of the CT in mediating F344 salt aversion was examined by testing NaCl preference after glossopharyngeal nerve (GL) transections, combined CT and GL deafferentation, and partial desalivation. Comparison with Wistar rats revealed that salt preference of F344 CTX rats followed a typical preference/aversion pattern across a range of NaCl concentrations. Studies of GL section, either alone or combined with CT sectioning, indicated that F344 rats' aversion was dependent on the integrity of the CT and not the GL. Removal of sublingual and submaxillary salivary glands did not lead to preference changes similar to those after CTX, indicating that the effects of CTX are not secondary to desalivation. Overall, the findings point to signals from the CT as playing a primary role in the NaCl aversion displayed by the intact F344 rat.

Sodium appetite after transection of the chorda tympani nerve in Wistar and Fischer 344 rats.

Acute sodium depletion in rats leads to dramatic increases in intake of hypertonic NaCl solutions, a behavior known as sodium appetite. The importance of signals conveyed by the chorda tympani (CT) nerve to the expression of sodium appetite is unclear. We examined the effects of bilateral CT transection on the short- and long-term response to sodium depletion in Wistar and Fischer 344 (F344) rat strains, because Wistar rats normally display a NaCl preference in the absence of need whereas F344 rats avoid NaCl. In both strains, sodium appetite after CT transection and treatment with the diuretic furosemide was delayed and blunted or eliminated. The results suggest that signals conveyed by the CT nerve are important in the expression of a sodium appetite. Effects on F344 rats are particularly interesting because CT transection surgery appears to have opposite effects on NaCl intake depending on whether F344 rats are sodium replete or deplete.

Reversal of the sodium chloride aversion of Fischer 344 rats by chorda tympani nerve transection.

Fischer 344 (F344) rats are atypical in their lack of preference for any concentration of NaCl solution over water. It was hypothesized that abnormal signals mediated by the chorda tympani nerve (CT) could be causally involved in NaCl avoidance by F344 rats. This study assessed whether CT transection would normalize the salt preference of F344 rats. Preference for NaCl solutions (0.6%, 0.8%, and 1.0%) versus water was assessed using two-bottle preference tests. At all concentrations tested, CT-transected animals preferred NaCl solutions to water. This preference differed dramatically from the avoidance of these solutions by controls. These findings are striking, particularly because CT transections have generally failed to significantly affect NaCl preference in other rat strains. The results are consistent with the hypothesis that in F344 rats the avoidance of the taste of NaCl stems from input mediated by the CT.

Is cimetidine being prescribed indiscriminately? An analytic survey of patients who present with symptoms of peptic ulcer disease.

An analytic survey was done to determine the influence of previously documented peptic ulcer disease (PUD) on the frequency of prescribing cimetidine to patients who present at a family medicine centre with symptoms of PUD. It was found that of 293 patients who presented with such symptoms over 1 year cimetidine was prescribed to 57 (19%). From the 236 patients who did not receive cimetidine 57 patients were selected at random for comparison. Information on these two groups of patients was obtained by chart review. The patients who received cimetidine were found to be significantly more likely (p less than 0.001) to have previously documented PUD than those who did not receive cimetidine. In patients in whom subsequent confirmation of PUD was not obtained, either because the results of investigations were negative or because the investigations were not ordered, cimetidine was prescribed to 63% of those who had previously documented PUD, compared with only 6% of those who did not. Of the patients who were investigated 73% of those with previously documented PUD had positive results, compared with 8% of those without previously documented PUD. The positive results were obtained by endoscopic examination in 88% of the patients with previously documented PUD, whereas upper gastrointestinal tract roentgenography was the definitive test in 73% of the patients without previously documented PUD. These findings suggest that previously documented PUD influences both the frequency of prescribing cimetidine and the investigations that are carried out.