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The effect of environmental enrichment in the CaMKIIT286A mutant mouse

Parsley, SL; (2006) The effect of environmental enrichment in the CaMKIIT286A mutant mouse. Doctoral thesis , UCL (University College London). Green open access

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The activity-dependent plasticity of synaptic strengths is believed to underlie learning and memory in the brain. One experimental form of synaptic plasticity is long-term potentiation (LTP), a phenomena that requires the actions of the highly abundant Ca2+/calmodulin-dependent protein kinase II (CaMKII). In support of the hypothesis that an LTP-like process may exist physiologically and be important for cognitive processing, hippocampal-dependent learning and memory are severely impaired in transgenic mice that possess a point-mutation (T286A) in the oc-isoform of CaMKII that blocks the ability of the kinase to autophosphorylate at residue Thr286 and exhibit Ca2+- independent activity. I have studied the properties of excitatory synaptic transmission in acute hippocampal brain slices from adult aCaMKIIT286A mutant mice and compared them to those from wild-type animals in order to investigate the consequences that may arise from the loss of CaMKII-dependent endogenous forms of synaptic plasticity. Surprisingly, no differences in the properties of evoked CA1 synaptic responses were found, suggesting that the loss of CaMKII function does not affect synaptic connectivity in these animals. To promote physiological brain plasticity and therefore the potential for detecting differences between the genotypes, mice were also raised in environmentally-enriched housing conditions. 3-5 weeks of enrichment did not affect the properties of evoked synaptic transmission in wild-type CA1 neurones and gross levels of excitatory input, assessed by median mEPSC amplitudes and measures of dendritic spine densities, were also unaffected. These neuronal properties were all significantly altered however, following environmental enrichment in the mutant animals. Thus, Thr286 autophosphorylation-independent forms of plasticity exist in vivo and are recruited by enriched experience in the mutant mouse. One explanation why such changes were not similarly observed in the wild-types may be that they are actively reversed by Thr286 autophosphorylation-dependent processes. In addition to impairing LTP, the T286A mutation may also impair homeostatic processes that act to maintain the properties of excitatory synaptic transmission in the mouse hippocampus.

Type: Thesis (Doctoral)
Title: The effect of environmental enrichment in the CaMKIIT286A mutant mouse
Identifier: PQ ETD:593099
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/1445775
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