Thesis--Gothenburg. / At head of title: From the Department of Histology, Medical Faculty, University of Göteborg, Sweden. Includes bibliographical references (p. 79-93).

Diss. (sammanfattning) Stockholm : Karol. inst., 2000. / Härtill 7 uppsatser.

No description available.

published_or_final_version / abstract / Biochemistry / Doctoral / Doctor of Philosophy

No description available.

No description available.

No description available.

Sensory axons from functionally related neurons often project to similar regions in the central nervous system (CNS). Various cell-cell interactions and activity-dependent mechanisms contribute to the formation of these arrangements, but it remains unclear how they ultimately influence circuit wiring and function. I examined mechanisms of somatosensory circuit assembly in Drosophila. In larvae, class III (cIII) and class IV (cIV) dendritic arborization neurons detect gentle touch and noxious stimuli, respectively. Sensory axons travel together to the CNS and terminate in the ventral nerve cord (VNC). Previous work showed that within the VNC, touch and nociceptive axons sort into adjacent layers and make modality-specific synaptic connections with a population of nociceptive interneurons. The organization of somatosensory afferents is similar in insects and vertebrates, but mechanisms underlying somatosensory circuit formation are not well understood. I identified a role for axon-axon interactions in modality-specific targeting and connectivity of touch neurons. Ablation of nociceptors resulted in touch neurons extending axons into the nociceptive region and expanding connectivity with nociceptive interneurons. By contrast, nociceptor axon targeting was not noticeably impacted by touch neuron ablation, suggesting that axon interactions act hierarchically to influence axon targeting. To understand how axon sorting emerges during development, I developed a method to perform time-lapse imaging of sensory axons during targeting. Preliminary results suggest that sensory axons arrive in the ventromedial neuropil sequentially based on target layer. I show that nociceptors also impact the transduction of touch stimulus. Whereas touch neuron activation normally elicits behaviors associated with touch stimulus, either ablation or silencing synaptic transmission in nociceptors led to behaviors associated with noxious stimuli. These results point to a possible role for neural activity in touch and nociceptive circuit wiring and function. In support of this, manipulating activity in touch or nociceptive neurons disrupted axon patterning. Additionally, I present a role for Down syndrome cell adhesion molecule 2 (Dscam2) in regulating connectivity between synaptic partners in the nociceptive circuit. Previous work showed that alternative splicing of Dscam2 generates two isoforms. I found that synaptic partners in the larval nociceptive circuit express complementary isoforms. Regulated alternative splicing of Dscam2 is required for robust nociceptive behavior and proper nociceptive axon patterning. Furthermore, forcing synaptic partners to express a common isoform resulted in nociceptive axon targeting defects. I propose that regulated expression of Dscam2 isoforms may be a mechanism to restrict connectivity to select groups of neurons. Taken together, these data support roles for axon-axon, axon-target, and possible activity-dependent mechanisms in somatosensory circuit assembly.

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Schwann cell-seeded guidance channels have been exploited to bridge and guide axonal re-growth across gaps in lesioned nerves. Mis-orientation of Schwann cells in the channels can however distort axonal growth within the lesion. We therefore propose to orient the growth of Schwann cells on aligned nanofibers such that axonal growth can be guided along the designated direction towards the target. Chitosan was the choice scaffold material given its biocompatibility and the tunable susceptibility to biodegradation. To be suitable for electrospinning, chitosan was dissolved in trifluoroacetic acid/methylene chloride solution. By replacing the grounded plate collector of the conventional electrospinning setup with parallel collector plates placed 1.6 cm apart, the positively charged chitosan fibersbecame alternately attracted to the parallel plates and ended up uniaxially aligned as fiber suspension across the plates. Stability of the chitosan fibers in aqueous, physiological environment was achieved with the use of sodium carbonate to neutralize residual acidity in the chitosan fiber preparation. Schwann cells seeded onto these stabilized aligned chitosan nanofibers aligned uniaxially with the chitosan nanofibers. In addition, by seeding dissociated cells of dorsal root ganglia (DRG, E14/15 rats) onto the uniaxially aligned nanofibers, both neurons and Schwann cells were aligned with uniaxial arrangement of nanofibers, and the Schwann cells showed myelination ofthe axons. A model of the chitosan nerve conduit was constructed with a core nanofiberbundle, and seeding of Schwann cells. Thesein vitro results provide proof-of-principle for pursuing improvement in post-traumatic recovery from nerve injury with use of uniaxially aligned chitosan nanofibers in Schwann cell-seeded nerve guidance channels. / published_or_final_version / Biochemistry / Master / Master of Philosophy