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Title: The role of activity in remodelling area-specific neocortical circuits during development
Author: Stacey, Jacqueline
ISNI:       0000 0004 7966 3017
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2018
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How sensory activity contributes to the development of the brain has been a long-standing question in neuroscience (Katz & Shatz, 1996). A recent study by Marques-Smith et al. (2016) showed that a transient translaminar cortical circuit exists in the primary somatosensory barrel field (S1BF). This connection consists of a reciprocal connection between L5b somatostatin Lpar1-EGFP interneurons onto layer 4 spiny stellate neurons. This transient L5b-L4 connection was observed to be modulated by perturbations of sensory input and appeared to be required for correct integration of thalamic afferents into layer 4 of the adult mouse (Marques-Smith et al., 2016). This circuit was, therefore, an ideal candidate to examine the role of sensory activity on circuit refinement. In this thesis I used laser scanning photo stimulation (LSPS) to map the developing L5b-L4 cortical circuit in the Celsr3jDlx5/6 mouse line, devoid of thalamocortical and corticothalamic connections, to investigate the role of sensory information during circuit development (Zhou et al., 2008). The presence and development of the L5b-L4 reciprocal circuit was found to occur independently of thalamic connections. It was hypothesised that the L5b-L4 circuit may exist as a ubiquitous developmental mechanism in other sensory areas, therefore I mapped developing cortical circuitry in the primary visual cortex (V1) of mice. In V1, the L5b-L4 connection was not present in either WT or Celsr3jDlx5/6 mice, suggesting that intrinsic cortical properties have a central role in neonatal circuit development. Due to S1BF and V1 circuitry differences, Lpar1-eGFP interneuron distributions and thalamic innervation were compared between the two regions. Both density and distribution of Lpar1-eGFP and SST+ cells differed between S1BF and V1. No timing differences in thalamic innervation were observed, however the cell types receiving direct thalamic input into layer 4 differed between S1BF and V1. These findings suggest that although sensory-evoked activity can remodel features such as barrels and ODCs, some aspects of initial cortical circuit formation in the first 2-3 weeks of a mouse's life does not require thalamic-driven input.
Supervisor: Butt, Simon ; Molnar, Zoltan Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available