No description available.

This study has investigated the role of neurokinin receptors, in particular the NK-1 receptor, in the regulation of excitability of SPN using selective agonists and antagonists. The whole-cell patch clamp technique was used to record from SPN in transverse slices of neonatal rat spinal cord <I>in vitro</I>. Neurones were positively identified as SPN due to their characteristic electrophysiological and morphological properties. Perfusion of the selective NK-1 receptor agonist GR73632 (25 nM-5μM; 2-120 s) induced concentration-dependent depolarising responses in SPN. The response to GR73632 (67% of SPN responsive) was maintained in the presence of TTX (250-500 nM), suggesting that NK-1 receptors are located directly upon SPN. The depolarising response to GR73632 was associated with an increase in neuronal input resistance, reduced with increasing membrane hyperpolarisation, and blocked by two selective NK-1 receptor antagonists, CP-99,994 (1-3 μM) and GR82334 (250 nM-1 μM). Excitatory postsynaptic potentials and strychnine-sensitive inhibitory postsynaptic potentials were also induced by GR73632 in approximately 10% of neurones. Application of GR73632 to a subpopulation of silent SPN induced rhythmical oscillations in membrane potential. The induction of oscillations following NK-1 receptor activation can lead to synchronised action potential firing within groups of SPN. This study has presented preliminary evidence to suggest that a presynaptic NK-1 receptor may exist upon the terminals of neurones which descend from supraspinal centres in synapse upon SPN. Activation of this subtype of NK-1 receptor was found to exert an inhibitory influence upon glutamatergic synaptic transmission to SPN. The results from this study suggest that activation of the NK-1 receptor may have a major excitatory effect upon the activity of SPN, probably by causing the closure of potassium channels open at rest.

No description available.

The gastrocnemius muscle was removed from the hindlimb of female rodents, minced into 1mm3 fragments and autotransplanted. Experimental groups had the sural or tibial nerves laid in the mince as follows: both nerves (BN), sural only (SN), tibial only (TN) or no nerve (NN). Animals were sacrificed 45 days postsurgery and the regenerate and contralateral muscles studied for fiber composition and aerobic capacity. Regenerate mass and aerobic capacity were significantly less than control and followed the order BN > TN > SN > NN. The percentage of Types I, IIA and IIB fibers were also different between treatment groups. The data suggests (1) either a more rapid development of axons associated with IIA fibers following nerve transection or greater reinnervation capacity, and/or (2) a shift in the relative number of these axons in the regenerating nerve.

In the peripheral nervous system the myelin sheath is produced by the spiral wrappings of the Schwann cell (SC) membrane around the axon. This provides insulation and increases the velocity of impulse propagation. The structure of myelin is maintained by a group of myelin proteins. Peripheral myelin protein-22 (PMP-22) is a 22 KDa glycoprotein, originally identified following nerve crush injury, that is found within SCs and is identical to the growth arrest specific protein GAS-3. The PMP-22 gene is regulated by two alternative promoters immediately upstream of two alternative non-coding exons. In order to study temporal and spatial expression of the PMP-22 gene and regulation of SC ensheathment and myelination, a transgenic mouse expressing the green fluorescent protein (GFP) driven by the myelin specific PMP-22 promoter was produced. To achieve this the PI promoter isolated from genomic DNA was initially incorporated into a plasmid containing the EGFP gene. In vitro transfection studies demonstrated appropriate expression of EGFP fluorescence. Microinjection of the transgene into pre- implantation fertilised embryos gave rise to three transgenic lines as confirmed by Southern blot and PGR. One founder expressed the transgene in a tissue specific manner. Mosaicism of expression both within an individual and between individuals was noted. In vitro manipulations showed that the expression patterns observed were independent of axonal contact and myelination but could be influenced by the extracellular matrix. These GFP expressing transgenic mice potentially provide a means to determine the dynamics of SC-axon interactions during myelination and the behaviour of transplanted SCs into myelin deficient regions and the SCs response to injury. Preliminary reports of this work are found in abstract form: British Neurosci. Assoc. Abstr., Vol 15, pi04, 1999.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2001. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

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

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 7 uppsatser.

Thesis (M.D.) -- University of Adelaide, Dept. of Human Physiology and Pharmacology, 1970.