Adjusting the thickness and internodal length of the myelin sheath is a mechanism for tuning the conduction velocity of axons to match computational needs. Interactions between oligodendrocyte precursor cells (OPCs) and developing axons regulate the formation of myelin around axons. We now show, using organotypic cerebral cortex slices from mice expressing eGFP in Sox10‐positive oligodendrocytes, that endogenously released GABA, acting on GABAA receptors, greatly reduces the number of oligodendrocyte lineage cells. The decrease in oligodendrocyte number correlates with a reduction in the amount of myelination but also an increase in internode length, a parameter previously thought to be set by the axon diameter or to be a property intrinsic to oligodendrocytes. Importantly, while TTX block of neuronal activity had no effect on oligodendrocyte lineage cell number when applied alone, it was able to completely abolish the effect of blocking GABAA receptors, suggesting that control of myelination by endogenous GABA may require a permissive factor to be released from axons. In contrast, block of AMPA/KA receptors had no effect on oligodendrocyte lineage cell number or myelination. These results imply that, during development, GABA can act as a local environmental cue to control myelination and thus influence the conduction velocity of action potentials within the CNS. GLIA 2017;65:309–321

Perception is an "inverse problem," in which the state of the world must be inferred from the sensory neural activity that results. However, this inference is both ill-posed (Helmholtz, 1856; Marr, 1982) and corrupted by noise (Green & Swets, 1989), requiring the brain to compute perceptual beliefs under conditions of uncertainty. Here we show that human observers performing a simple visual choice task under an externally imposed loss function approach the optimal strategy, as defined by Bayesian probability and decision theory (Berger, 1985; Cox, 1961). In concert with earlier work, this suggests that observers possess a model of their internal uncertainty and can utilize this model in the neural computations that underlie their behavior (Knill & Pouget, 2004). In our experiment, optimal behavior requires that observers integrate the loss function with an estimate of their internal uncertainty rather than simply requiring that they use a modal estimate of the uncertain stimulus. Crucially, they approach optimal behavior even when denied the opportunity to learn adaptive decision strategies based on immediate feedback. Our data thus support the idea that flexible representations of uncertainty are pre-existing, widespread, and can be propagated to decision-making areas of the brain.

Many scientists, healthcare providers, policy makers, and patients highly anticipate the application of biomedical technologies such as functional neuroimaging to the prediction, diagnosis, and treatment of mental disorders. The potential efficacy of such applications is controversial, and functional neuroimaging is not yet routinely used in psychiatric clinics. However, commercial ventures and enthusiastic reporting indicate a pressing need to engage with the social and ethical issues raised by clinical translation. There has been little investigation of how individuals living with mental illness view functional neuroimaging, or of the potential psychological impacts of its clinical use. We conducted 12 semi-structured interviews with adults diagnosed with major depression or bipolar disorder, probing their experiences with mental healthcare and perspectives on the prospect of receiving neuroimaging for prediction, diagnosis, and treatment planning. Participants discussed the potential role of neuroimages in 1) mitigating stigma; 2) supporting morally-loaded explanations of mental illness due to an imbalance of brain chemistry; 3) legitimizing psychiatric symptoms through objective representations of disorder; and 4) reifying disorder categories and links to identity. We discuss these anticipated outcomes in the context of participant lived experience and attitudes to biologisation of mental illness, and argue for bringing these voices into upstream ethics discussion.