Investigating the organizing principles of the mouse claustrum

Thesis

The claustrum is highly interconnected with many structures in the brain, but the organizing principles governing its vast connectivity have yet to be fully explored. In this thesis, I investigate the architecture of circuits between the claustrum and neocortex and within the claustrum itself. Immunohistochemistry, neuronal tract tracing, in vitro whole-cell patch-clamp electrophysiology, dual-color optogenetic circuit mapping, and in vivo calcium imaging of neural activity were used to assess whether claustrum neurons combine inputs from multiple cortical areas and what impact claustrum neurons have on the cortex. I determined that individual claustrum neurons frequently integrate inputs from more than one cortical site, most commonly between regions of the frontal cortex. Additionally, I found that neurons in the claustrum receive inputs from an array of sensory and associative cortical areas, albeit to a lesser extent. Neuronal tract tracing and electrophysiology further indicated that input integration from frontal cortical regions depends on the cell type and output target of claustrum neurons. Optogenetic mapping revealed that intraclaustral connectivity was far more frequent than previously reported, particularly among neurons that did not share the same output target. Finally, activity in claustrum axons recorded with in vivo calcium imaging showed responses to combinations of sensory stimuli that were then transmitted to downstream cortical targets. My findings shed light on the organizing principles of claustrum connectivity, demonstrating that individual claustrum neurons integrate afferent inputs and redistribute this information back to cortex after performing output target- and cell-type-dependent local computations.

Authors: Shelton, AM

• DOI: 10.5287/ora-pmjeaynbz
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: in vivo imaging; neuronal tract tracing; electrophysiology; optogenetics; neuroscience; claustrum
• Subjects: Neurosciences