Bhatt, Karan (2013) Molecular basis for memory storage and addiction. MTech thesis.
This thesis is mainly divided into two parts. In the first part, a mathematical model of the bistable switch is developed with the help of which a zone is defined where the CaMKII − PP1 switch remains bistable. For each pair of CaMKII and PP1, the critical stimulus concentration and the active CaMKII concentration is calculated which leads to autophosphorylation of CaMKII. The change in the critical stimulus and active CaMKII with respect to CaMKII and PP1 is also plotted. The critical stimulus concentration increases in a linear manner with change in CaMKII and PP1 for the upper limit while it changes randomly for the lower limits. For active CaMKII, the change is of sigmoidal nature in case of both upper and lower limits for CaMKII and PP1. A novel correlation is developed for measuring the critical stimulus intensity required for CaMKII to undergo direct autophosphorylation which leads to long term memory formation with a goodness of fit 99.74 %. In the second part of the thesis, a mechanism is proposed for the inhibition of morphine on long-term potentiation of GABA-A mediated synaptic transmission (LTP-GABA). Morphine binding on µ − opioid receptors on the presynaptic GABAergic cells results in inhibition of activation of sGC by blocking the NO binding site. Retrogradely travelling NO is not able to bind sGC and activates it in the presence of morphine which results in the inhibition of activation of cGMP and PKG. As a result, LTP-GABA is not produced which increases the chances of addiction. A mathematical model is presented for morphine inhibition on LTP-GABA and its implication in addiction. A two step model of sGC activation is used, where morphine inhibits the NO during the first step and consequently blocks sGC activation. The dependence of morphine inhibition on various parameters such as morphine dissociation, morphine concentration, NO removal and rate of inhibition is also studied.
|Item Type:||Thesis (MTech)|
|Uncontrolled Keywords:||Memory storage; CaMKII; bistable switch; sGC; addiction.|
|Subjects:||Engineering and Technology > Biomedical Engineering|
|Divisions:||Engineering and Technology > Department of Biotechnology and Medical Engineering|
|Deposited By:||Hemanta Biswal|
|Deposited On:||17 Dec 2013 16:32|
|Last Modified:||17 Dec 2013 16:32|
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