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David L Hill

Publications and source records attributed to David L Hill.

15 recordsLinked to original sources

Gustatory terminal field organization and developmental plasticity in the nucleus of the solitary tract revealed through triple-fluorescence labeling.

Early dietary sodium restriction has profound influences on the organization of the gustatory brainstem. However, the anatomical relationships among multiple gustatory nerve inputs have not been examined. Through the use of triple-fluorescence labeling and confocal laser microscopy, terminal fields of the greater superficial petrosal (GSP), chorda tympani (CT), and glossopharyngeal (IX) nerves were visualized concurrently in the nucleus of the solitary tract (NTS) of developmentally sodium-restricted and control rats. Dietary sodium restriction during pre- and postnatal development resulted in a twofold increase in the volume of both the CT and the IX nerve terminal fields but did not affect the volume of the GSP terminal field. In controls, these nerve terminal fields overlapped considerably. The dietary manipulation significantly increased the overlapping zones among terminal fields, resulting in an extension of CT and IX fields past their normal boundaries. The differences in terminal field volumes were exaggerated when expressed relative to the respective NTS volumes. Furthermore, increased terminal field volumes could not be attributed to an increase in the number of afferents because ganglion cell counts did not differ between groups. Taken together, selective increases in terminal field volume and ensuing overlap among terminal fields suggest an increased convergence of these gustatory nerve terminals onto neurons in the NTS. The genesis of such convergence is likely related to disruption of cellular and molecular mechanisms during the development of individual terminal fields, the consequences of which have implications for corresponding functional and behavioral alterations.

Animals↗

In vivo recordings from rat geniculate ganglia: taste response properties of individual greater superficial petrosal and chorda tympani neurones.

Coding of gustatory information is complex and unique among sensory systems; information is received by multiple receptor populations located throughout the oral cavity and carried to a single central relay by four separate nerves. The geniculate ganglion is the location of the somata of two of these nerves, the greater superficial petrosal (GSP) and the chorda tympani (CT). The GSP innervates taste buds on the palate and the CT innervates taste buds on the anterior tongue. To obtain requisite taste response profiles of GSP neurones, we recorded neurophysiological responses to taste stimuli of individual geniculate ganglion neurones in vivo in the rat and compared them to those from the CT. GSP neurones had a distinct pattern of responding compared to CT neurones. For example, a small subset of GSP neurones had high response frequencies to sucrose stimulation, whereas no CT neurones had high response frequencies to sucrose. In contrast, NaCl elicited high response frequencies in a small subset of CT neurones and elicited moderate response frequencies in a relatively large proportion of GSP neurones. The robust whole-nerve response to sucrose in the GSP may be attributable to relatively few, narrowly tuned neurones, whereas the response to NaCl in the GSP may relate to proportionately more, widely tuned neurones. These results demonstrate the diversity in the initial stages of sensory coding for two separate gustatory nerves involved in the ingestion or rejection of taste solutions, and may have implications for central coding of gustatory quality and concentration as well as coding of information used in controlling energy, fluid and electrolyte homeostasis.

Action Potentials↗

Fluorescence in situ hybridization reanalysis of day-6 human blastocysts diagnosed with aneuploidy on day 3.

OBJECTIVE: To determine the concordance of day-6 blastocyst analysis with the day-3 fluorescence in situ hybridization (FISH) aneuploidy diagnosis. DESIGN: Retrospective study. SETTING: In vitro fertilization laboratory. PATIENT(S): Six hundred sixty embryos were included from 94 IVF/intracytoplasmic sperm injection patients undergoing preimplantation genetic diagnosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Single blastomeres biopsied on day 3. Aneuploidy screening for chromosomes 13, 18, 21, X, and Y were analyzed. Left-over blastocysts were reanalyzed on day 6. RESULT(S): Among the 660 embryos evaluated, 367 (55.6%) were euploid and 281 (42.6%) were aneuploid. Of the euploid embryos, 213 embryos were transferred, 68 were frozen on day 5, and 86 were left. All 281 aneuploid embryos were further cultured, and 55 (19.6%) progressed to blastocysts. When FISH reanalysis was performed, 33 of 55 blastocysts (60%) were confirmed aneuploid in concordance with the day-3 diagnosis. However, 22 of 55 blastocysts (40%) were determined to be euploid. In addition, 207 aneuploid embryos (73.7%) arrested before day 6, as opposed to 32 of the 86 euploid embryos (37.2%). CONCLUSION(S): Day-3 single-cell embryo biopsy reveals that aneuploidy can be confirmed in 60.7% of the blastocysts on reanalysis. The majority of discordance is most likely due to embryo mosaicism and possibly a limited ability to "self-correct."

Aneuploidy↗

Each sensory nerve arising from the geniculate ganglion expresses a unique fingerprint of neurotrophin and neurotrophin receptor genes.

Neurons in the geniculate ganglion, like those in other sensory ganglia, are dependent on neurotrophins for survival. Most geniculate ganglion neurons innervate taste buds in two regions of the tongue and two regions of the palate; the rest are cutaneous nerves to the skin of the ear. We investigated the expression of four neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and NT-4, and five neurotrophin receptors, trkA, trkB, trkC, p75, and truncated trkB (Trn-B) in single sensory neurons of the adult rat geniculate ganglion associated with the five innervation fields. For fungiform papillae, a glass pipette containing biotinylated dextran was placed over the target papilla and the tracer was iontophoresed into the target papilla. For the other target fields, Fluoro-Gold was microinjected. After 3 days, geniculate ganglia were harvested, sectioned, and treated histochemically (for biotinylated dextran) or immunohistochemically (for Fluoro-Gold) to reveal the neurons containing the tracer. Single labeled neurons were harvested from the slides and subjected to RNA amplification and RT-PCR to reveal the neurotrophin or neurotrophin receptor genes that were expressed. Neurons projecting from the geniculate ganglion to each of the five target fields had a unique expression profile of neurotrophin and neurotrophic receptor genes. Several individual neurons expressed more than one neurotrophin receptor or more than one neurotrophin gene. Although BDNF is significantly expressed in taste buds, its primary high affinity receptor, trkB, was not prominently expressed in the neurons. The results are consistent with the interpretation that at least some, perhaps most, of the trophic influence on the sensory neurons is derived from the neuronal somata, and the trophic effect is paracrine or autocrine, rather than target derived. The BDNF in the taste bud may also act in a paracrine or autocrine manner on the trkB expressed in taste buds, as shown by others.

Animals↗

Neuron/target plasticity in the peripheral gustatory system.

Taste bud volume on the anterior tongue in adult rats is matched by an appropriate number of innervating geniculate ganglion cells. The larger the taste bud, the more geniculate ganglion cells that innervate it. To determine if such a match is perturbed in the regenerated gustatory system under different dietary conditions, taste bud volumes and numbers of innervating neurons were quantified in adult rats after unilateral axotomy of the chorda tympani nerve and/or maintenance on a sodium-restricted diet. The relationship between taste bud size and innervation was eliminated in rats merely fed a sodium-restricted diet; individual taste bud volumes were smaller than predicted by the corresponding number of innervating neurons. Surprisingly, the relationship was disrupted in a similar way on the intact side of the tongue in unilaterally sectioned rats, with no diet-related differences. The mismatch in these groups was due to a decrease in average taste bud volumes and not to a change in numbers of innervating ganglion cells. In contrast, individual taste bud volumes were larger than predicted by the corresponding number of innervating neurons on the regenerated side of the tongue; again, with no diet-related differences. However, the primary variable responsible for disrupting the function on the regenerated side was an approximate 20% decrease in geniculate ganglion cells available to innervate taste buds. Therefore, the neuron/target match in the peripheral gustatory system is susceptible to surgical and/or dietary manipulations that act through multiple mechanisms. This system is ideally suited to model sensory plasticity in adults.

Animals↗

Taste bud cell dynamics during normal and sodium-restricted development.

Taste bud volume increases over the postnatal period to match the number of neurons providing innervation. To clarify age-related changes in fungiform taste bud volume, the current study investigated developmental changes in taste bud cell number, proliferation rate, and life span. Taste bud growth can largely be accounted for by addition of cytokeratin-19-positive taste bud cells. Examination of taste bud cell kinetics with 3H-thymidine autoradiography revealed that cell life span and turnover periods were not altered during normal development but that cells were produced more rapidly in young rats, a prominent modification that could lead to increased taste bud size. By comparison, dietary sodium restriction instituted during pre- and postnatal development results in small taste buds at adulthood as a result of fewer cytokeratin-19-positive cells. The dietary manipulation also had profound influences on taste bud growth kinetics, including an increased latency for cells to enter the taste bud and longer life span and turnover periods. These studies provide fundamental, new information about taste bud development under normal conditions and after environmental manipulations that impact nerve/target matching.

Animals↗

What regulations for preimplantation genetic diagnosis?

PURPOSE: To discuss the qualifications of personnel involved in either (a) embryo biopsy/slide fixation, (b) performance of preimplantation genetic diagnosis-specific assays, or (c) interpretation of findings and results from such studies. METHODS: Illustrate similarities and differences between the qualifications and licensing requirements for personnel involved in high complexity testing in other laboratory specialities, such as microbiology or endocrinology. RESULTS: Parallels can in fact be drawn between specific personnel certification and licensing requirements for reporting test results following preimplantation genetic testing and those for other clinical specimens submitted for testing. CONCLUSIONS: Assisted reproductive technology programs generally do not have personnel certified in cytotechnology or clinical genetics. Programs that perform the actual interpretation of specimens submitted for evaluation by fluorescent in situ hybridization will have to have supervisory personnel certified to perform such interpretations to ensure the level of quality control and assurance now afforded in centers for assisted reproductive technology.

Female↗

Neural plasticity in the gustatory system.

Sensory systems adapt to changing environmental influences by coordinated alterations in structure and function. These alterations are referred to as plastic changes. The gustatory system displays numerous plastic changes even in receptor cells. This review focuses on the plasticity of gustatory structures through the first synaptic relay in the brain. Unlike other sensory systems, there is a remarkable amount of environmentally induced changes in these peripheral-most neural structures. The most consistent and largest changes occur to stimuli that also impact on homeostatic systems, especially when the environmental manipulation is instituted during early development.

Animals↗

Injury-induced functional plasticity in the peripheral gustatory system.

Combining unilateral denervation of anterior tongue taste buds with a low-sodium diet in rats results in a rapid, dramatic, and selective attenuation of neurophysiological sodium taste responses from the intact side of the tongue. The transduction pathway responsible for the attenuated response is through the epithelial sodium channel (Hill and Phillips, 1994). Current experiments extend these findings by detailing the effects of experimentally induced injury on taste responses from anterior tongue taste receptors in sodium-restricted rats. Experiments focused on functional salt taste responses from the intact chorda tympani nerve in sodium-restricted rats in which a gustatory nerve was sectioned that innervates the anterior tongue (chorda tympani), the posterior tongue (glossopharyngeal), or palatal taste receptors (greater superficial petrosal) or in which a nongustatory nerve was sectioned that also has its target in the anterior tongue (trigeminal). An additional group was studied that received thermal injury to the anteroventral tongue. Substantial and selective suppression of sodium salt responses occurred in a graded manner generally related to the distance from the target field of the injury to anterior tongue taste buds. The order of effectiveness was: chorda tympani section > trigeminal section > thermal injury = glossopharyngeal section > greater superficial petrosal section. These results support the hypothesis that local, diffusible factors liberated from immune-derived cells as a result of neural and/or epithelial damage are involved in regulating the transduction pathway responsible for sodium salt sensation, and that these factors may become evident through dietary sodium restriction.

Animals↗

Time course of morphological alterations of fungiform papillae and taste buds following chorda tympani transection in neonatal rats.

The time course of structural changes in fungiform papillae was analyzed in rats that received unilateral chorda tympani nerve transection at 10 days of age. Morphological differences between intact and denervated sides of the tongue were first observed at 8 days postsection, with an increase in the number of fungiform papillae that did not have a pore. In addition, the first papilla with a filiform-like appearance was noted on the denervated side at 8 days postsectioning. By 11 days after surgery, the total number of papillae and the number of papillae with a pore were significantly lower on the transected side of the tongue as compared to the intact side. At 50 days postsection, there was an average of 70.5 fungiform papillae on the intact side and a mean of only 20.8 fungiform papillae the denervated side. Of those few remaining papillae on the cut side, an average of 13.5 papillae were categorized as filiform-like, while no filiform-like papillae occurred on the intact side. Significant reduction in taste bud volume was noted at 4 days posttransection and further decrements in taste bud volume were noted at 8 and 30 days postsection. Electron microscopy of the lingual branch of the trigeminal nerve from adult rats that received neonatal chorda tympani transection showed normal numbers of both myelinated and unmyelinated fibers. Thus, in addition to the well-characterized dependence of taste bud maintenance on the chorda tympani nerve, the present study shows an additional role of the chorda tympani nerve in papilla maintenance during early postnatal development.

Animals↗

Is gender selection an appropriate use of medical resources?

Gender selection by PGD is an appropriate use of medical resources. Children borne through PGD for gender determination would be welcome and would come into a couple's life at a planned, opportune time. If the practice were made more available through insurance coverage, the size and makeup of families could become a matter of choice rather than chance for couples favoring this approach.

Family Characteristics↗

Sensitive periods for the effect of dietary sodium restriction on intact and denervated taste receptor cells.

Unilateral chorda tympani nerve (CT) section combined with dietary sodium restriction leads to striking alterations in sodium taste function. The regenerated rat CT exhibits deficits in sodium sensitivity, and surprisingly, there are also functional alterations in the intact, contralateral nerve. The studies presented here describe the functional "sensitive periods" for these aberrations and the number of taste buds present during corresponding stages. The regenerated CT is sensitive to dietary sodium restriction during the first 2 wk after denervation, whereas the intact CT is sensitive to dietary manipulation during the first week postsection. Therefore, distinct mechanisms are responsible for the effects of sodium restriction combined with denervation, because separate sensitive periods exist for the regenerated and intact CT nerves. Identification of mature taste buds with an antibody directed at anti-keratin 19 revealed that there is a loss of ~85% of taste buds on the denervated side of the tongue under control and low-sodium diets within the first week postsection. Thus, sodium restriction does not differentially affect the loss of taste buds following denervation.

Animals↗