Visual Cortical Circuit Dynamics in Health and Disease

Yu Tang, Purdue University

Abstract

Vision is one of the most important senses to guide behaviors, and visual functions heavily rely on the underlying neuronal circuits. The mouse visual cortex has diverse roles in encoding not only visual information, but also visually related non-visual information after learning. Its diverse functions are attributed to the dynamic functional circuits, which undergo plastic changes not only during development and learning but also during post-injury recovery throughout life. My thesis work revolves around characterizing plastic functional circuits in the mouse visual cortex using silicon probe recordings, and it covers neuronal circuit dynamics in normal visual familiarization, diseased conditions, as well as post-injury recovery. Visual perceptual experience induces 4-8 Hz oscillations in mouse V1, which extend beyond the visual stimulation window and may encode visual familiarity. Such 4-8 Hz oscillations could reflect top-down effects and visual working memory, and may mediate inter-areal communications across visual cortical areas. To explore whether the oscillations exist and modulate activities across multiple visual cortical areas, we recorded simultaneous activities in V1 and one of the higher order visual areas (HVA), lateromedial (LM) and anterolateral (AL) areas, at a time. Following the visual perceptual experience, 4-8 Hz oscillations were enhanced in V1, as well as in both LM and AL superficial layers. After familiarization of the stimulus that maximally induced visually locked response in LM, V1 local field potentials (LFPs) became more persistently phase locked to LFPs in LM in 4-8 Hz range, but not to LFPs in AL. In parallel, after familiarization of the stimulus that maximally induced visually locked response in AL, V1 became more persistently phase-locked to AL, but not LM, in 4-8 Hz. Unit population became to spike at more consistent 4-8 Hz phases in response to the entrained spatial frequency (SF) and temporal frequency (TF), regardless of their cortical origins. Furthermore, V1 units and HVA units showed higher spiking synchrony, especially for the post-stimulus responding units, and the post-stimulus firing peaks in V1 were reduced when HVAs were optogenetically inactivated. These results demonstrated that visual experience induced persistent 4-8 Hz LFP synchrony between V1 and the HVA that had functional preference matched with the entrained SF and TF, which was accompanied by stronger 4-8 Hz modulated unit spiking and higher spiking synchrony between V1 and HVAs. Neural circuits underlying brain functions are vulnerable to damage, including ischemic injury, leading to neuronal loss and gliosis. Recent technology of direct conversion of endogenous astrocytes into neurons in situ can simultaneously replenish the neuronal population and reverse the glial scar. However, whether these newly reprogrammed neurons undergo normal development, integrate into the existing neuronal circuit, and acquire functional properties specific for this circuit is not known. We investigated the effect of NeuroD1-mediated in vivodirect reprogramming on functional recovery in a mouse model of ischemic injury. After performing electrophysiological extracellular recordings, we discovered that visual cortex acquired direct visual responses, and fast spiking units exhibited delayed recovery of visual responses. Furthermore, units’ orientation selectivity sharpened over time after NeuroD1 delivery, and optogenetically tagged converted neurons exhibited selective responses to orientations. Our results show that visual cortical responses recovered and acquired selectivity to orientations after NeuroD1 mediated gene therapy.

Degree

Ph.D.

Advisors

Pluta, Purdue University.

Subject Area

Communication|Medicine

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