EASTBIO The role of neural connectivity in motor control

Motor control is a critical feature that enables behaviour. Implementation of motor commands relies on complex neural circuits, and connective tracts found within the brain and the spinal cord. Maintenance of connectivity among the brain areas required for the execution of moments is a prerequisite for successfully carrying out behavioural tasks. Alterations in synaptic connectivity can trigger diseases affecting the motor system^1-2, and both inhibitory¹ and excitatory² synapses undergo morphological and functional changes leading to specific phenotypes¹. Munc 13-1 is a key protein present at the synaptic level, which plays a pivotal role in the maintenance of connectivity between neurons³. Munc 13-1 was reported to be downregulated in the presence of genetic mutations, highlighting it as an important target for future investigations in disorders affecting the motor system. However, little is known about the role of Munc 13-1 in the developing and adult motor system. Thus, the present project aims to elucidate the role of Munc 13-1 in the maintenance of motor functions. Mouse genetics will be used to target inhibitory and excitatory neurons known to control the speed and the rhythm of locomotion, and the flexor and extensor alternation. Downregulation of Munc 13-1 will be achieved in inhibitory or excitatory neurons utilising a cre-lox strategy in transgenic mice. A similar approach has been previously used to investigate the role of Munc 13-1 in dopaminergic neurons with the mice remaining viable³. In this project, we do not expect downregulation of Munc 13-1 to be embryonically lethal due to the restricted expression of En1 and Chx10 to specific neuronal populations within the motor system. The phenotype of the newly generated mice will be investigated by machine learning-based analysis of motor functions¹; here, gait analysis will elucidate potential changes in motor control caused by downregulation of Munc 13-1 gene. Moreover, electrophysiological properties of inhibitory and excitatory neurons will be investigated in ex vivo preparations to further understand the impact of Munc 13-1 downregulation on the motor circuits. Finally, anatomical analysis will be performed to assess potential synaptic changes and cell loss in the Munc 13-1 deficient mice. We anticipate that this project will unravel the role of the Munc 13-1 in maintaining connectivity and functionality within the motor system. 

HOW TO APPLY

Application instructions can be found on the EASTBIO website- http://www.eastscotbiodtp.ac.uk/how-apply-0

1)     Download and complete the Equality, Diversity and Inclusion survey.

2)     Download and complete the EASTBIO Application Form.

3)     Submit an application to St Andrews University through the Online Application Portal

Your online application must include the following documents:

-         Completed EASTBIO application form

-         2 References (to be completed on the EASTBIO Reference Form, also found on the EASTBIO website)

-         Academic Qualifications

-         English Language Qualification (if applicable)

Unfortunately due to workload constraints, we cannot consider incomplete applications. Please make sure your application is complete by 27^th November 2023

 CONTACT

Queries on the project can be directed to the project supervisor.

Queries on the application process can be directed to Rachel Horn at [Email Address Removed]

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