No description available.

No description available.

The emergence of limbs in vertebrates represents a significant evolutionary innovation. Limbs facilitate diverse motor behaviors, yet require spinal networks that can coordinate the activities of many individual muscles within the limb. Here I describe several efforts to characterize the specification of spinal motor neurons and assembly of spinal circuits in higher vertebrates. I discuss the formation of selective presynaptic sensory inputs to motor pools, a process which has long been thought to occur in an activity-independent manner. I demonstrate an as yet unappreciated role of activity-dependent refinement in patterning the set of sensory-motor connections that link motor pools with synergist function. I also explore the genetic specification of motor pools that project to defined muscle targets. I show that the motor pools that control digits engage distinct developmental genetic programs which reflect underlying differences in Hox and retinoic acid signaling. The divergent mechanisms underlying the specification of digit-innervating motor neurons may reflect the unique status of digit control in the evolution of motor behavior.

Extracellular potentials due to firing of action potentials are computed around cortical neurons and populations of cortical neurons. These extracellular potentials are calculated as a sum of contributions from ionic currents passing through the cell membrane at various locations using Maxwell's equations in the quasi-static limit. These transmembrane currents are found from simulations of anatomically reconstructed cortical neurons implemented as multi-compartmental models in the simulation tool NEURON. Extracellular signatures of action potentials of single neurons are calculated both in the immediate vicinity of the neuron somas and along vertical axes. For the neuronal populations only vertical axis distributions are considered. The vertical-axis calculations were performed to investigate the contributions of action potential firing to laminar-electrode recordings. Results for high-pass (750 - 3000 Hz) filtered potentials are also given to mimic multi-unit activity (MUA) recordings. Extracellular traces from single neurons and populations (both synchronous and asynchronous) of neurons are shown for three different neuron types: layer 3 pyramid, layer 4 stellate and layer 5 pyramid cell. The layer 3 cell shows a 'closed-field' configuration, while the layer 5 pyramid demonstrates an 'open-field' appearance for singe neuron simulations which is less apparent in population simulations. The layer 4 stellate cell seems to fall somewhere in between the open- and closed-field scenarios. Comparing single neuron and synchronous populations, the amplitudes of the extracellular traces increase as population radii increase, though the shapes are generally similar. Asynchronous populations produce small amplitudes due to a time convolution of various neuron contributions. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2005

The morphology of C3, a motoneuron mediating the tentacle withdrawal reflex, was investigated in the snail Helix aspersa by intracellular injections of the tracers Neurobiotin and biocytin. Axonal projections were identified in the optic nerve, the olfactory nerve, the internal peritentacular nerve, the external peritentacular nerve, the cerebral-pedal connective and the cerebral commissure. A rare characteristic of the cell was the multibranching of axons in the neuropil and the exiting of this bundle of fibres into the cerebral-pedal connective. Dendritic arborizations were observed branching from the cell body, the axon hillock and the dorsal main axon. In addition, tufts of dendrites were seen to branch from the ventral axon. Based on its morphology, C3 is probably a central component in the avoidance behaviour, receiving sensory input at extensive dendritic sites and sending axons to a number of key effector sites to co-ordinate the chain of reactions that constitutes the snail's avoidance behaviour.

Master of Philosophy (Medicine) / The actin cytoskeleton is important in many cellular processes such as motility, and establishing and maintaining cell morphology. Members of the tropomyosin protein family associate with the actin cytoskeleton along the major groove of actin filaments (F-actin), stabilising them and regulating actin-filament dynamics. To date over 40 non-muscle tropomyosin isoforms have been identified, which are encoded by 4 different genes (α, β, γ, δ). Individual tropomyosin isoforms define functionally distinct F-actin populations. Previous studies have shown that tropomyosins sort to distinct subcellular compartments at different stages of development in polarised cells. Neuronal growth cones are highly dynamic polarised structures, dependent on a constant reorganisation of the actin cytoskeleton. By eliminating tropomyosins in a knockout (KO) mouse model, we investigated the role of two tropomyosin isoforms, Tm5NM1 and Tm5NM2 (γTm gene products) in growth cone dynamics and neurite outgrowth. Growth cone protrusion rates were significantly increased in one day old Tm5NM1/2 KO hippocampal neurons compared to WT controls. Neuritogenesis was significantly affected by the elimination of Tm5NM1/2, with a slight decrease in neurite length and an increase in neuronal branching in neurons cultured for four days. At the molecular level, the depletion of Tm5NM1/2 had no impact on the protein levels and activity of ADF/cofilin in hippocampal neurons while in cortical neurons a subtle but significant increase in ADF/cofilin activity was observed. The subtle phenotype in the early stages of neuritogenesis observed from eliminating Tm5NM1/2 may be explained with functional compensation by other tropomyosin isoforms. Functional compensation for the loss of Tm5NM1/2 may be provided by isoforms Tm5a/5b, TmBr2 and Tm4 as they localise to the growth cones, structures where Tm5NM1/2 are normally found. These results suggest that Tm5NM1/2 may not be required for early stages of neuritogenesis but may still play a fine-tuning role for this process.

Master of Philosophy (Medicine) / The actin cytoskeleton is important in many cellular processes such as motility, and establishing and maintaining cell morphology. Members of the tropomyosin protein family associate with the actin cytoskeleton along the major groove of actin filaments (F-actin), stabilising them and regulating actin-filament dynamics. To date over 40 non-muscle tropomyosin isoforms have been identified, which are encoded by 4 different genes (α, β, γ, δ). Individual tropomyosin isoforms define functionally distinct F-actin populations. Previous studies have shown that tropomyosins sort to distinct subcellular compartments at different stages of development in polarised cells. Neuronal growth cones are highly dynamic polarised structures, dependent on a constant reorganisation of the actin cytoskeleton. By eliminating tropomyosins in a knockout (KO) mouse model, we investigated the role of two tropomyosin isoforms, Tm5NM1 and Tm5NM2 (γTm gene products) in growth cone dynamics and neurite outgrowth. Growth cone protrusion rates were significantly increased in one day old Tm5NM1/2 KO hippocampal neurons compared to WT controls. Neuritogenesis was significantly affected by the elimination of Tm5NM1/2, with a slight decrease in neurite length and an increase in neuronal branching in neurons cultured for four days. At the molecular level, the depletion of Tm5NM1/2 had no impact on the protein levels and activity of ADF/cofilin in hippocampal neurons while in cortical neurons a subtle but significant increase in ADF/cofilin activity was observed. The subtle phenotype in the early stages of neuritogenesis observed from eliminating Tm5NM1/2 may be explained with functional compensation by other tropomyosin isoforms. Functional compensation for the loss of Tm5NM1/2 may be provided by isoforms Tm5a/5b, TmBr2 and Tm4 as they localise to the growth cones, structures where Tm5NM1/2 are normally found. These results suggest that Tm5NM1/2 may not be required for early stages of neuritogenesis but may still play a fine-tuning role for this process.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 3 uppsatser.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2004. / Restricted until October 2005. Bibliography: leaves 71-94.