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Article

Jeremy C. Borniger and Luis de Lecea

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.

Article

Luis Carrillo-Reid and Rafael Yuste

Despite over a century of neuroscience research, the nature of the neural code, that is, how neuronal activity underlies motor, sensory, and cognitive functions, remains elusive. Understanding the causal relation between neuronal activity and behavior requires a new conceptual paradigm that considers groups of neurons, instead of individual neurons, as the functional building blocks of the brain. These “neuronal ensembles,” defined as groups of neurons with coordinated activity that are reliably recalled by sensory stimuli, motor programs, or cognitive states, could be basic modular functional units of neural circuits. This hypothesis is consistent with past and present neuroscience results and could provide a broader framework to more effectively decipher the neural code in normal brains and provide new insights into how abnormal brain activity could lead to mental and neurological disease.