Hormonal Effects on Neurons

Modulation of visual cortical processing by brain-generated estrogen
2012 Seed Grant
Raphael Pinaud, Ph.D.
Department of Neurobiology
Northwestern University

Humans are highly visual animals and loss of any visual function can severely impact quality of life. Visual problems are among the ten most prevalent causes of disability in America and can affect all populations at all ages. In children, visual problems can be congenital and are often associated with developmental delays requiring significant intervention. Similarly, adults (and especially the elderly) whose vision is failing due to age, disease or injury have severely disrupted life styles and require special care. This places a significant burden on society to support those with impaired vision and much effort has been expended to alleviate visual deficits to improve quality of life. The studies detailed here, will provide a novel mechanisms that has the potential to prove very important for both understanding visual processing and later intervening clinically to improve vision. Thus these studies will be highly significant for the visual science community and beyond because:
  • Dr. Pinaud and his laboratory aim to understand the effects of a critical and highly modulated hormone on visual function: Estrogen is a potent hormone with strong significance for both male and female physiology. Recently, its effects on the central nervous system have been the subject of great interest as it is becoming increasingly clear that estrogen can be produced in sensory circuits, in an activity-dependent manner, and consequently modulate neuronal function in a rapid timescale leading to altered behavior. While, sensory effects of gonadal estrogen have long been suspected in humans, there has been no work exploring the direct effects of rapid, estrogenic signaling on visual cortical processing, and no work directly studying estrogen produced in the brain. Understanding such signaling will have broad implications for both the basic neurobiology of vision as well as clinical applications where estrogenic treatments are applied for other reasons (e.g., anti-estrogen chemotherapy, contraceptives, menopause).
  • Dr. Pinaud is exploring novel basic mechanisms of sensory function, and novel ways to study hormonal modulation of neuronal physiology: His studies directly focus at uncovering the mechanisms by which a steroid hormone modulates the physiology of neurons, and neuronal ensembles. Thus, his work brings a new perspective to study questions that have been pursued in classic models for decades. This new perspective holds the promise to uncover novel principles and mechanisms by which hormones modulate sensory processing and, more broadly, impact neuronal physiology. His proposal also explores the potential of new operational rules (hormonal modulation) of sensory system function.
  • Dr. Pinaud is exploring a novel mechanism of hormone regulation and action within visual cortex: This proposal emphasizes that visual dysfunction related to lowered E2 levels is a process that may occur entirely (or partially) in the brain, as opposed to the prevalent view that altered processing stems primarily from problems in the periphery. This represents a novel and unique perspective on the function of sensory systems. As such, his work highlights the importance of seriously considering brain-based mechanisms of visual dysfunction, and not just those that are primarily due to transduction (retinal) problems. Furthermore, this proposal is expected to open discussions on the use of estrogen-replacement therapy to modulate or recover visual dysfunction associated with estrogen insufficiency.

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