Popke, D. | bioRxiv Science

bioRxiv2021

Binocular vs. monocular recovery experience differentially promote recovery from visual deficits in a mouse model of amblyopia

Altered visual experience during monocular deprivation (MD) profoundly changes in ocular dominance (OD) in the developing primary visual cortex (V1). MD-driven changes in OD are an experimental model of amblyopia, where early-life alterations in vision lead visual disruption in adulthood. Current treatments for amblyopia include patching of the dominant eye, and more recently-developed binocular therapies. However, the relative impact of monocular vs. binocular recovery experiences on recovery of function in V1 is not well understood. Using single-unit recording, we compared how binocular recovery [BR] or reverse occlusion [RO] of identical duration and content affects OD and visual response recovery in mouse binocular V1 after a period of MD. We also tested how BR and RO affected MD-driven alterations of parvalbumin expression, and visually-driven expression of cFos in parvalbumin-positive and negative neurons. Finally, we tested how BR and RO affected recovery of normal visual acuity for the two eyes in the context of visually-driven behavior. We find that BR is quantitatively superior with respect to normalization of V1 neurons OD, visually-driven cFos expression, and visual acuity for the two eyes. However, MD-driven changes in the firing rate and response properties of V1 principal neuron and fast-spiking interneuron populations do not recover fully after either BR or RO. Binocular matching of orientation preference also remains disrupted in V1 neurons after both forms of recovery experience. Thus BR and RO, analogs of differing treatment regimens for amblyopia, differentially impact various aspects of visual recovery in a mouse model for amblyopia. Significance StatementAmblyopia resulting from altered childhood eye function is a leading cause of lifelong vision loss. Treatment typically involves patching of the dominant eye (forcing monocular visual experience), and produces only partial recovery of vision. Using a well-established mouse model of amblyopia, we directly compared how two types of visual experiences influence recovery of visual function. Our findings suggest that binocular vs. monocular visual experience differentially effect restoration of normal visual responses in cortical neurons, visually-driven neuronal gene expression, and visual acuity. Understanding how the quality of recovery experience impacts visual system recovery in amblyopia should provide critical insights for clinical strategies for its treatment.

neuroscience↗

bioRxiv2020

Sleep loss drives brain region- and cell type-specific alterations in ribosome-associated transcripts involved in synaptic plasticity and cellular timekeeping

Sleep and sleep loss are thought to impact synaptic plasticity, and recent studies have shown that sleep and sleep deprivation (SD) differentially affect gene transcription and protein translation in the mammalian forebrain. However, much less is known regarding how sleep and SD affect these processes in different microcircuit elements within the hippocampus and neocortex - for example, in inhibitory vs. excitatory neurons. Here we use translating ribosome affinity purification (TRAP) and in situ hybridization to characterize the effects of sleep vs. SD on abundance of ribosome-associated transcripts in Camk2a-expressing (Camk2a+) pyramidal neurons and parvalbumin-expressing (PV+) interneurons in mouse hippocampus and neocortex. We find that while both Camk2a+ neurons and PV+ interneurons in neocortex show concurrent SD-driven increases in ribosome-associated transcripts for activity-regulated effectors of plasticity and transcriptional regulation, these transcripts are minimally affected by SD in hippocampus. Similarly we find that while SD alters several ribosome-associated transcripts involved in cellular timekeeping in neocortical Camk2a+ and PV+ neurons, effects on circadian clock transcripts in hippocampus are minimal, and restricted to Camk2a+ neurons. Taken together, our results indicate that SD effects on transcripts destined for translation are both cell type- and brain region-specific, and that these effects are substantially more pronounced in the neocortex than the hippocampus. We conclude that SD-driven alterations in the strength of synapses, excitatory-inhibitory balance, and cellular timekeeping are likely more heterogeneous than previously appreciated. Significance StatementSleep loss-driven changes in transcript and protein abundance have been used as a means to better understand the function of sleep for the brain. Here we use translating ribosome affinity purification (TRAP) to characterize changes in abundance of ribosome-associated transcripts in excitatory and inhibitory neurons in mouse hippocampus and neocortex after a brief period of sleep or sleep loss. We show that these changes are not uniform, but are generally more pronounced in excitatory neurons than inhibitory neurons, and more pronounced in neocortex than in hippocampus.

neuroscience↗