Rossi, Luigi Frederico; (2018) Cortical circuits for visual processing and epileptic activity propagation. Doctoral thesis (Ph.D), UCL (University College London).

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	Video Suppl Movie 6.1_Interictal events montage.mp4 - Supplemental Material Download (4MB)
	Video Suppl Movie 6.2_Seizures Montage.mp4 - Supplemental Material Download (21MB)
	Video Suppl Movie 6.3_ Hilbert analysis of 6-11Hz movie.mp4 - Supplemental Material Download (19MB)
	Video Suppl Movie 6.4_Cycle average of 6-11Hz oscillations.mp4 - Supplemental Material Download (306kB)
	Video Supplementary Movie 8.1_Seizures and Cortical Spreading Depression (2X real time).mp4 - Supplemental Material Download (66MB)

Abstract

The thesis focuses on the relationship between cortical connectivity and cortical function. The first part investigates how the fine scale connectivity between visual neurons determines their functional responses during physiological sensory processing. The second part ascertains how the mesoscopic scale connectivity between brain areas constrains the spread of abnormal activity during the propagation of focal cortical seizures. Part 1: Neurons in the primary visual cortex (V1) are tuned to retinotopic location, orientation and direction of motion. Such selectivity stems from the integration of inputs from hundreds of presynaptic neurons distributed across cortical layers. Yet, the functional principles that organize such presynaptic networks have only begun to be understood. To uncover them, I used monosynaptic rabies virus tracing to target a single pyramidal neuron in L2/3 (starter neuron) and trace its presynaptic partners. I combined this approach with two-photon microscopy in V1 to investigate the relationship between the activity of the starter cell, its presynaptic neurons and the surrounding excitatory population across cortical layers in awake animals. Part 2: Focal epilepsy involves excessive and synchronous cortical activity that propagates both locally and distally. Does this propagation follow the same functional circuits as normal cortical activity? I induced focal seizures in primary visual cortex (V1) of awake mice, and compared their propagation to the retinotopic organization of V1 and higher visual areas. I measured activity through simultaneous local field potential recordings and widefield calcium imaging, and observed prolonged seizures that were orders of magnitude larger than normal visual responses. I demonstrate that seizure start as standing waves (synchronous elevated activity in the focal V1 region and in corresponding retinotopic locations in higher areas) and then propagate both locally and into distal regions. These regions matched each other in retinotopy. I conclude that seizure propagation respects the connectivity underlying normal visual processing.

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