Principal Supervisor: Professor Bruno Frenguelli, School of Life Sciences
Co-supervisor: Dr. Elliot Ludvig, Department of Psychology
PhD project title: Molecular mechanisms of cellular and behavioural adaptations to environmental enrichment in mammals (In vivo skills-appropriate project)
University of Registration: University of Warwick
Environmental enrichment is known to alter neuronal structure and function and to improve cognitive ability in experimental rodents.
However, the mechanisms regulating the neuronal response to enrichment are not known. We have made the exciting discovery that a protein kinase, MSK1, which regulates gene transcription via phosphorylation of CREB and histone H3, is required for the enhancement of synaptic transmission after enrichment. We now wish to extend these observations to investigate further the MSK1-dependent cellular, molecular and genomic mechanisms engaged by environmental enrichment throughout the lifespan.
In this project we will raise wild-type and MSK1 mutant mice in either standard or enriched environments where the mice have access to toys, tunnels, running wheels and a larger number of cage mates. These mice will be compared in terms of their performance on tests of cognitive function, with electrophysiological and morphological analysis of neuronal function and anatomy and next-generation sequencing providing cellular and molecular insight into the effects of enrichment on the mammalian brain. The role played by MSK1 in these processes will be inferred from deficits observed in the behaviour and neuronal structure/function of MSK1 mutant mice.
These studies are important as they will help to define the cellular and molecular mechanisms activated by positive environmental influences and the role played by MSK1. Such knowledge is required if we are to attempt to design drugs or behavioural therapies to mimic the effects of enrichment, which may be of value in elderly people suffering from cognitive decline.
- Hunter CJ et al., (2017) MSK1 regulates transcriptional induction of Arc/Arg3.1 in response to neurotrophins. FEBS Open Bio. 7 821-834. doi: 10.1002/2211-5463.12232.
- Daumas S et al., (2017) The kinase function of MSK1 regulates BDNF signaling to CREB and basal synaptic transmission, but is not required for hippocampal long-term potentiation or spatial memory. eNeuro. 4. pii: doi: 10.1523/ENEURO.0212-16.2017.
- Correa, S.A., et al., (2012) MSK1 regulates homeostatic and experience-dependent synaptic plasticity. Journal of Neuroscience. 32 p.13039-51.
BBSRC Strategic Research Priority: Molecules, Cells and Systems
Techniques that will be undertaken during the project:
- Behavioural analysis
- Biochemical analyses
- Next Generation Sequencing
- Quantitative biology/Bioinformatics
Contact: Professor Bruno Frenguelli, School of Life Sciences