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Investigating changes in neuronal development and connectivity in a mouse model of muscimol-induced perinatal brain injury


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  Dr H Stolp, Dr C Thornton  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

MRes Project 

Disruption of normal brain development during pregnancy and in infancy can lead to life-long neurological disorders. As the brain develops, there is increasing complexity of cellular structure, connectivity and functional activity. This pattern is essential for normal brain development and disruption to these early developmental processes leads to long-term dysfunction, including neurodevelopmental disorders such as epilepsy, and autismspectrum disorder (ASD). Recent work from our lab has shown that alteration in GABAergic signaling, using Muscimol, during early neuronal development in vitro alters the morphological and physiological development of neurons, creating networks that appear to be less complex but hyperexcitable. In vivo, a similar pharmacological intervention results in early changes in brain structure, and behavioural differences in adults that suggest social deficits or depressive-like behaviour. However, the structural connectivity of the brain that links brain volume changes with behavioural deficits are yet to be determined. The specific aim of this study is to determine the deficits in neuronal morphology that underly brain injury produced by developmental exposure to a GABAA receptor agonist. As part of this, dendritic arborization, dendritic spine number and the number of chemically mature synapses will be assessed. The successful candidate will join the Neurodevelopmental Injury lab, based at the RVC Camden campus, and gain expertise in primary culture, live and fixed cell microscopy, immunohistochemistry, protein and RNA analyses. Outcomes: This work will provide an important link between cellular complexity during development and behavioural differences detected in adulthood. The specific structural changes that occur, and the time and sexdependence of these changes, have important implications in the treatment of neurodevelopmental disorders. 


Funding Notes

Partially funded MRes project: e.g. the lab will cover the project costs, and the MRes student will be expected to meet the course fees and their living expenses.
International applicants are welcome to apply but must be able to fund the difference between "Home" and "Overseas" tuition fees.
Please see website for more details.

References

Goikolea-Vives, A. and H. B. Stolp (2021). "Connecting the Neurobiology of Developmental Brain Injury: Neuronal
Arborisation as a Regulator of Dysfunction and Potential Therapeutic Target." Int J Mol Sci 22(15).
Stolp, H. B., et al. (2019). "Interneuron Development Is Disrupted in Preterm Brains With Diffuse White Matter Injury:
Observations in Mouse and Human." Front Physiol 10: 955.
Zhao, H., et al. (2021). "GABAergic System Dysfunction in Autism Spectrum Disorders." Front Cell Dev Biol 9: 781327.
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