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Biomedical subjects

Thomas K M Lee

Publications and source records attributed to Thomas K M Lee.

7 recordsLinked to original sources
PubMed2006

An identified central pattern-generating neuron co-ordinates sensory-motor components of respiratory behavior in Lymnaea.

Defining the attributes of individual central pattern-generating (CPG) neurons underlying various rhythmic behaviors are fundamental to our understanding of how the brain controls motor programs, such as respiration and locomotion. To this end, we have explored a simple invertebrate preparation in which the neuronal basis of respiratory rhythmogenesis can be investigated from the whole animal to a single cell level. An identified dopaminergic neuron, termed right pedal dorsal 1 (RPeD1), is a component of the CPG network which controls hypoxia-driven, aerial respiration in the fresh water snail Lymnaea stagnalis. Using intact, semi-intact and isolated brain preparations, we have discovered that in addition to its role as a respiratory CPG neuron, RPeD1 co-ordinates sensory-motor input from the pneumostome (the respiratory orifice) at the water/air interface to initiate respiratory rhythm generation. An additional, novel role of RPeD1 was also found. Specifically, direct intracellular stimulation of RPeD1 induced pneumostome openings, in the absence of motor neuronal activity. To determine further the role of RPeD1 in the respiratory behavior of intact animals, either its axon was severed or the soma selectively killed. Many components of the respiratory behavior in the intact animals were found to be perturbed following RPeD1 axotomy or 'somatomy' (soma removed). Taken together, the data presented provide a direct demonstration that RPeD1 is a multifunctional CPG neuron, which also serves many additional roles in the control of breathing behavior, ranging from co-ordination of mechanosensory input to the motor control of the respiratory orifice.

Action Potentials↗
PubMed2005

A new case of oculoectodermal syndrome.

An 11-month-old infant girl presented with right-sided features of aplasia cutis congenita of the scalp, unilateral epibulbar dermoids, eccentric pupil, coloboma of the right upper eyelid, and depigmentation of the fundus surrounding the right optic nerve. These findings were similar to the oculoectodermal syndrome reported by other clinicians and researchers.

Coloboma↗
PubMed2004

Transplantation and restoration of functional synapses between an identified neuron and its targets in the intact brain of Lymnaea stagnalis.

Most information available to date regarding the cellular and synaptic mechanisms of target cell selection and specific synapse formation has primarily come from in vitro cell culture studies. Whether fundamental mechanisms of synapse formation revealed through in vitro studies are similar to those occurring in vivo has not yet been determined. Taking advantage of the regenerative capabilities of adult molluscan neurons, we demonstrate that when transplanted into the host ganglia an identified neuron reestablishes its synaptic connections with appropriate targets in vivo. This synaptogenesis, however, was possible only if the targets were denervated from the host cell. Specifically, the giant dopamine neuron right pedal dorsal 1 (RPeD1) located in the pedal ganglia was isolated from a donor brain and transplanted into the visceral ganglia of the recipient brain. We discovered that within 2-4 days the transplanted RPeD1 exhibited extensive regeneration. However, simultaneous intracellular recordings failed to reveal synapses between the transplanted cell and its targets in the visceral ganglia, despite physical overlap between the neurites. To test whether the failure of a transplanted cell to innervate its target was due to the fact that the targets continued to receive input from the native RPeD1, the latter soma was surgically removed prior to the transplantation of RPeD1. Even after the removal of host soma, the transplanted RPeD1 failed to innervate the targets such as visceral dorsal 4 (VD4)-despite extensive regeneration by the transplanted cell. However, when RPeD1 axon was allowed to degenerate completely, the transplanted RPeD1 successfully innervated all of its targets and these synapses were similar to those seen between host RPeD1 and its targets. Taken together, our data demonstrate that the transplanted cells will innervate their potential targets only if the targets were denervated from the host cell. These data also lend support to the idea that, irrespective of their physical location in the brain, the displaced neurons are able to regenerate, recognize their targets, and establish specific synapses in the nervous system.

Animals↗
PubMed2003

Clinical diagnoses that overlap with choroideremia.

PURPOSE: To understand which clinical presentations suggest a diagnosis of choroideremia (CHM). METHODS: Retrospective chart review. Included were patients for whom a clinical diagnosis of CHM was suggested, but either protein analysis or direct sequencing of the CHM gene could not confirm the diagnosis. Clinical presentation, family history and fundus photographs were reviewed. RESULTS: We analyzed protein and DNA samples from members of more than 100 families in which at least 1 member had a clinical diagnosis of CHM. For 26 of these families, the clinical diagnosis of CHM could not be confirmed by laboratory analysis. Relevant clinical information was requested from the referring ophthalmologists so that alternative diagnoses could be considered. Sufficient information was provided for 13 of the 26 families. Four patients were reclassified as having retinitis pigmentosa (RP) from the clinical phenotype; only two clearly had X-linked inheritance. One patient had a syndrome including macular dystrophy, hearing loss, developmental delay and cerebral palsy. One patient was reclassified as having congenital stationary night blindness on the basis of an electronegative electroretinogram and a normal fundus. One patient had hearing loss suggesting Usher syndrome. One patient had signs consistent with cone-rod dystrophy (CRD). Five patients could not be reclassified on the basis of the clinical presentation. CONCLUSION: RP, Usher syndrome and CRD are clinical phenotypes that may overlap with CHM. Clinical features that suggest CHM include severe chorioretinal atrophy with preservation of the macula, X-linked inheritance and retinal changes in a related female.

Adaptor Proteins, Signal Transducing↗
PubMed2003

A novel syndrome of congenital lid and punctal anomalies, corneal and chorioretinal dystrophy.

A 28-year old woman had an ocular syndrome consisting of congenital lid and punctal anomalies, and corneal and chorioretinal dystrophy without facial dysmorphism. These combined malformations of the ocular adnexae and both anterior and posterior ocular segments have not been previously described and appear to represent a novel syndrome. Direct sequencing of PAX6 and the DNA-binding domain of FOXC1 failed to detect a mutation.

Adult↗
PubMed2002

Specificity of synapse formation between Lymnaea heart motor neuron and muscle fiber is maintained in vitro in a soma-muscle configuration.

Precise neuronal connectivity during development is subservient to all nervous system functions in adult animals. However, the cellular mechanisms that mastermind this neuronal connectivity remain largely unknown. This lack of fundamental knowledge regarding nervous system development is due in part to the immense complexity of mammalian brain, as cell-cell interactions between defined sets of pre- and postsynaptic partners are often difficult to investigate directly. In this study, we developed a novel model system which has allowed us to reconstruct synapses between identified motor neurons and their target heart muscle cell in a soma-muscle configuration. Utilizing this soma-myocardial cell synapse model, we demonstrate that synapses between somata and heart muscle cells can be reconstructed in cell culture. The soma-myocardial cell synapses required 12-24 h to develop and thus differed temporally from conventional neuromuscular synapses (seconds to a few minutes). We also demonstrate that the synapses are target cell-type-specific and are most likely independent of transmitter phenotypic characteristics of presynaptic neurons.

Animals↗