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Title: Connectivity-specified targeting and manipulation of the motor thalamus
Author: Shah, Rahul Surendra
ISNI:       0000 0004 9347 9216
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2020
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Understanding the nature and consequences of information flow between the basal ganglia, cerebellum, thalamus and motor cortex on the acquisition and execution of motor skills may lead to better circuit therapies for brain disorders. Although basal ganglia and cerebellar output is thought to influence motor cortex activity via projections arising from distinct zones of ventral ‘motor’ thalamic nuclei (ventral medial [VM], ventral anterior [VA] and ventral lateral [VL] nuclei), the consequences of their activity on motor skills in rodents remains uncertain. Here, we first utilise an anterograde transsynaptic viral strategy to confirm that anatomically and functionally distinct basal ganglia-recipient and cerebellar-recipient neuron populations exist in the mouse motor thalamus. To address the behavioural significance of these two neuron populations for motor skill learning, Vglut2-Cre mice with either targeted chronic motor thalamus silencing (using overexpression of the inward-rectifier potassium channel Kir2.1) or acute optogenetic silencing of VM or VL (using the light-sensitive proton pump ArchT) thalamus were trained in a novel operant task monitoring the self-paced acquisition of a covert, temporally-constrained lever press sequence (fixed ratio of 3 lever presses within 2 seconds [FR3/2s]) over multiple sessions. Surprisingly, rather than causing gross motor impairment or impaired acquisition of the FR3/2s action pattern, mice receiving acute VM-ArchT silencing or chronic motor thalamus silencing showed faster early learning of the sequence compared to controls or VL-ArchT silencing. Simultaneous adaptation of peak within-press acceleration with learning was deficient in mice receiving VL-ArchT silencing. Our results suggest that manipulating the motor thalamus in mice can alter the pattern of within-day and between-day performance gains during task acquisition, potentially via downstream network effects which promote learning occurring via competing circuits.
Supervisor: Sharott, Andrew ; Magill, Peter ; Brown, Peter Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Motor cortex ; Movement sequences ; Cerebral cortex ; Electrophysiology ; Transgenic mice ; Cerebellum ; Basal ganglia ; Thalamus ; Neurosciences