The hypocretins (also known as orexins) are selectively expressed in a subset of lateral hypothalamic neurons. Since the reports of their discovery in 1998, they have been intensely investigated in relation to their role in sleep/wake transitions, feeding, reward, drug abuse, and motivated behavior. This research has cemented their role as a subcortical relay optimized to tune arousal in response to various salient stimuli. This article reviews their discovery, physiological modulation, circuitry, and integrative functionality contributing to vigilance state transitions and stability. Specific emphasis is placed on humoral and neural inputs regulating hcrt neural function and new evidence for an autoimmune basis of the sleep disorder narcolepsy. Future directions for this field involve dissection of the heterogeneity of this neural population using single-cell transcriptomics, optogenetic, and chemogenetics, as well as monitoring population and single cell activity. Computational models of the hypocretin network, using the “flip-flop” or “integrator neuron” frameworks, provide a fundamental understanding of how this neural population influences brain-wide activity and behavior.
Jeremy C. Borniger and Luis de Lecea
In 1903, standing at the dawn of the 20th century, W. E. B. Du Bois wrote that the color line is the defining characteristic of American society. Well into the 21st century, Du Bois’s prescience sadly still rings true. Even when a society is built on a commitment to equality, and even with the election of its first black president, the United States has been unsuccessful in bringing about an end to the rampant and violent effects of racism, as numerous acts of racial violence in the media have shown. For generations, scholars of color, among them Ralph Ellison, James Baldwin, and Franz Fanon, have maintained that whiteness lies at the center of the problem of racism. It is only relatively recently that the critical study of whiteness has become an academic field, committed to disrupting racism by problematizing whiteness as a corrective to the traditional exclusive focus on the racialized “other.” Critical Whiteness Studies (CWS) is a growing field of scholarship whose aim is to reveal the invisible structures that produce and reproduce white supremacy and privilege. CWS presumes a certain conception of racism that is connected to white supremacy. In advancing the importance of vigilance among white people, CWS examines the meaning of white privilege and white privilege pedagogy, as well as how white privilege is connected to complicity in racism. Unless white people learn to acknowledge, rather than deny, how whites are complicit in racism, and until white people develop an awareness that critically questions the frames of truth and conceptions of the “good” through which they understand their social world, Du Bois’s insight will continue to ring true.