Primary Supervisor: Dr Todor Gerdjikov, Department of Neuroscience, Psychology and Behaviour

Secondary supervisor: Jian Liu

PhD project title: Decoding movement from single neurons in motor cortex and their subcortical targets

University of Registration: University of Leicester

Project outline:

Background: Fine motor control involves the ability to reach, grasp and release objects. It is a fundamental aspect of motor behaviour essential for feeding, self-care and the manipulation of tools. Fine motor control is impaired in a number of neurological conditions and an understanding of the underlying neuronal mechanisms in the intact brain can help advance our knowledge of these conditions. Further, computational approaches are used to decode movement parameters from neural signals in an attempt to explain how this structure may control movement generation (e.g., Xing et al., 2019). In rat motor cortex, electrophysiological studies show a broadly somatotopic representation of different body parts (the ‘motor ratunculus’ in parallel to the human ‘motor homunculus’) with clear rich representations of the forelimb region (e.g. Galinanes et al., 2018). This is illustrated in the following schematic of the rat brain (taken from Ebbesen et al., 2018; DOI: https://doi.org/10.1523/JNEUROSCI.1671-18.2018):

However currently we do not have a good understanding of how fine reaching and grasping movements are orchestrated by motor cortex. There is clear evidence that lesioning motor cortex affects movement and that fine motor skill learning affects cortical plasticity. Surprisingly however, little further progress has been made in understanding how specific movement parameters (speed, trajectory, etc.) are encoded in single neurons in this structure and its downstream targets. This is a significant gap in our knowledge of the brain mechanisms of natural movements. To characterize the relationship between movement parameters and motor cortex activity, we have previously recorded the activity of motor cortex single neurons in rats performing a motor task (Gerdjikov et al., 2013). This work uncovered a surprising set of motor cortex neurons whose activity shows a weak relationship to movement parameters and instead appears related to movement monitoring. This work parallels primate recordings, which also show a variety of motor cortex responses to fine movements.

Objectives: The purpose of the current project is to investigate novel approaches for decoding movement parameters from neural data acquired from morphologically distinct motor cortex neurons. Using computational approaches we will investigate the relationship between forelimb movement kinetics and neural activity in subpopulations of output-defined motor cortex neurons.

Methods: Firstly, we will link activity in discrete output-defined M1 neuronal populations to movement parameters in rats trained in a skilled reaching task (illustrated in this YouTube video from the University of Lethbridge, Canada: https://www.youtube.com/watch?v=NZwM9bop02w). This aspect of the work will rely on modern viral approaches to separately tag neurons belonging to different projections and record their activity in behaving rats using fibre photometry and/or extracellular neurophysiology. Computational approaches such as machine learning will be used to decode kinematics derived from movement data.

A second aspect of the work will involve causal experiments where we will use optogenetics to selectively ‘turn off’ the activity of discrete projections. We will investigate how these manipulations affect fine motor control in behaving rats to causally tease apart the contribution of each projection to motor control.

References:

1. Galinanes GL, Bonardi C, & Huber D (2018). Directional reaching for water as a cortex-dependent behavioral framework for mice. Cell reports, 22(10), 2767-2783.
2. Gerdjikov TV, Haiss F, Rodriguez-Sierra O, Schwarz C (2013). Rhythmic whisking area (RW) in rat primary motor cortex: an internal monitor of movement-related signals? Journal of Neuroscience. 33:14193-204.
3. Xing, D., Aghagolzadeh, M., Truccolo, W., & Borton, D. (2019). Low-Dimensional Motor Cortex Dynamics Preserve Kinematics Information During Unconstrained Locomotion in Nonhuman Primates. Frontiers in neuroscience, 13.

BBSRC Strategic Research Priority: Understanding the Rules of Life: Neuroscience and behaviour

Techniques that will be undertaken during the project:

• In vivo neurophysiology and imaging
• Rodent behavioural testing
• Rodent microsurgery
• Neural data modelling and analysis

Contact: Dr Todor Gerdjikov, University of Leicester