published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy

The currents generated by excitatory and inhibitory synapses on motoneurons can be amplified by noradrenalin and serotonin. Both of these neurotransmitters act, and interact, via the same Gq-protein second-messenger system to modulate L-type Ca++, persistent-Na+, and leak K+ channels on motoneuron dendrites. However, noradrenergic and serotonergic synapses only modulate nearby excitatory and inhibitory synapses, so their relative distributions play a major role in the regulation of the overall output of the motoneuron. Moreover, the relative proximity between noradrenergic and serotonergic synapses may allow their individual effects to combine nonlinearly when co-activated, thereby regulating the magnitude of the amplification. The goal of the present study is to determine whether the distributions of noradrenergic and serotonergic synapses are biased along motoneuron dendritic trees. The dendritic trees of five intracellularly stained feline splenius motoneurons were reconstructed. On them were plotted the locations of noradrenergic and serotonergic contacts, as determined by immunohistochemistry. The distribution of noradrenergic contacts was moderately biased both dorsally and distally in all five cells. Serotonergic contacts on the same neurons showed a moderate ventral bias. These findings suggest that excitatory and inhibitory inputs located dorsally and/or distally are preferentially amplified by noradrenergic synapses. Also, those synapses which are located ventrally are favorably amplified by serotonergic synapses. Both serotonergic and noradrenergic contacts are strongly biased towards innervation along small diameter (<2μm) dendrites. The relative distributions between serotonergic and noradrenergic contacts have also been analyzed for all five cells. There was a bias towards minimizing the distance between like contacts (NE to NE and 5-HT to 5-HT). This increases the likelihood of interaction within populations when contacts are co-activated. Conversely, the distances between neighbouring noradrenergic and serotonergic contacts (NE to 5-HT and 5-HT to NE) were biased towards greater separation. This decreases the likelihood of interaction between populations when contacts are co-activated. In summary, these findings suggest that noradrenalin and serotonin, having different location biases along the dendritic tree, will amplify some synapses in a biased manner. Additionally, like synapses may work in a coordinated manner with respect to their relative proximity. Coordination between noradrenergic and serotonergic synapses is less likely. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2008-09-29 09:59:38.799

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5-hydroxytryptamin (5-HT) is biochemically derived from Tryptophan. Kynurenic acid and quinolinic acid are also known metabolites of tryptophan. 5-HT is considered to play a role in depression and today selective serotonin reuptake inhibitors (SSRIs) are used for treatment of depression. 5-HT may also play a role in pain perception. The aim of this study was to investigate whether a supplement of tryptophan may affect conditions such as depression and/or pain. Reviewed studies show that tryptophan deficiency leads to less availability of tryptophan in the brain, which reduces the synthesis of serotonin. Lowering of mood appears and seems to be linked to the decrease in serotonin synthesis. Supplements of tryptophan have in some studies been shown to have effects on social behaviour with reduced quarrelsome behaviour and increased dominant behaviour. Corresponding studies on the effects on pain provide a complex picture. Results indicate that in acute pain 5- HT seems to provide some pain relief but contradictory responses to 5-HT are seen in neuropathic and inflammatory pain. Comorbidity with both depression and pain occur, and has been linked to the increase in tryptophan metabolism through the kynurenine pathway. Enzymatic modifications have been detected which lead to elevated kynurenine/tryptophan ratios. This seems relevant to this comorbidity. Tryptophan as a supplement for effects on conditions such as depression and/or pain is very uncertain because of the complexity in physiological responses. More studies are needed. / Tryptofan är utgångsmaterial för syntesen av 5-hydroxytryptamin (5-HT) men metaboliseras även till andra metaboliter så som kynureninsyra och kinolinsyra. 5- HT anses ha betydelse vid depression och idag används selektiva serotoninåterupptagshämmare (SSRI) mot depression. 5-HT har eventuellt betydelse vid upplevelsen av smärta också. Syftet med studien var att undersöka om ett tillskott av tryptofan kan påverka sjukdomstillstånd som depression och/eller smärta. Granskade studier visar att tryptofanbrist leder till mindre tillgänglighet av tryptofan i hjärnan vilket minskar syntesen av serotonin. Förändrat stämningsläge visas och tycks vara kopplat till den minskade serotoninsyntesen. Tryptofantillskott har i vissa studier visats ha inverkan på socialt beteende med minskat stridslystet beteende samt ökat dominant beteende. Motsvarande studier för att studera effekten på smärta ger en komplex bild. Resultat visar på att vid akut smärta verkar 5-HT ha en viss smärtlindring och motsägelsefulla svar på 5-HT ses vid neuropatisk samt inflammatorisk smärta. Samsjuklighet med både depression och smärta förekommer och har kunnat kopplas till ökad tryptofanmetabolism via kynurenin -vägen. Enzymatiska förändringar har upptäckts och leder till förhöjt kynurenin /tryptofan förhållande. Detta förefaller av betydelse för denna samsjuklighet. Tryptofan som ett kosttillskott för inverkan på sjukdomstillstånd som depression och/eller smärta är väldigt osäkert då komplexiteten hur de fysiologiska svaren blir av ett tillskott är för stor och fler studier behövs göras.

No description available.

Thesis (M.S. in Interdisciplinary Studies: Neurogenetics)--Vanderbilt University, Dec. 2007. / Title from title screen. Includes bibliographical references.

Thesis (M.A.)--Baylor University, 2007. / In abstract "h and 2" are subscript. Includes bibliographical references (p. 43-52).

Thesis (Ph. D.)--Georgia State University, 2007. / Title from file title page. Donald H. Edwards, committee chair; Charles D. Derby, Paul S. Katz, Kathryn Betty Grant, committee members. Electronic text (226 p. : ill. (some col.)) : digital, PDF file. Description based on contents viewed Feb. 6, 2008. Includes bibliographical references (p. 208-221).

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 4 uppsatser.