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Title: Connectivity and integrative properties of layer 5 neurons in the mouse visual cortex
Author: Galloni, Alessandro Roberto
ISNI:       0000 0004 9353 4115
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2020
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A central question in neuroscience is how expectations shape sensory processing. In the cerebral cortex, feedforward connections convey sensory information, while feedback connections are thought to be crucial for directing attention, signaling contextual information, and enabling perceptual inference. Thick-tufted layer 5 (ttL5) pyramidal neurons play an important role in integrating sensory, internal, and motor information. They have large complex morphologies that receive thousands of synaptic inputs from across the brain, and express a diverse set of active conductances which support highly nonlinear dendritic computations. Their axons also form the largest output pathway from the cerebral cortex, making them ideally positioned to integrate and summarise cortical computations to drive behaviour. In this thesis, I perform whole-cell patch clamp recordings to characterize the intrinsic properties of a population of ttL5 neurons in the medial secondary visual cortex (V2m) of mice, genetically labelled in the Glt25d2-Cre line. These neurons are found to form a homogeneous population with integrative properties that are broadly consistent with several known features of ttL5 neurons. The inputs to Glt25d2-Cre neurons in V2m are found to originate in several brain regions, associated with both sensory and internal representations. Using optogenetics and spatially patterned optical stimulation, I map the spatial distributions of synapses from these regions on the dendritic trees of the ttL5 neurons. These inputs target distinct dendritic domains in a pattern that argues against classical notions of hierarchical connectivity. By electrically stimulating the largest input populations, I show that these pathways display synaptic facilitation and sum linearly across a wide range of temporal intervals. Furthermore, I find that Ca(2+)-mediated supralinearities, such as backpropagation-activated spike bursts, which have been extensively described in primary visual and somatosensory cortex, are absent in V2m neurons. Finally, through a combination of electrophysiological recordings, morphological reconstructions, and computational modelling, I show that dendritic excitability in ttL5 neurons is modulated by apical trunk length. In summary, I thoroughly describe the properties of a new ttL5-specific mouse line and provide new evidence that ttL5 neuron properties and canonical notions of hierarchical connectivity are not universally applicable throughout the cortex.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available