Adaptive Value Normalization in the Prefrontal Cortex Is Reduced by Memory Load.

Adaptation facilitates neural representation of a wide range of diverse inputs, including reward values. Adaptive value coding typically relies on contextual information either obtained from the environment or retrieved from and maintained in memory. However, it is unknown whether having to retrieve and maintain context information modulates the brain's capacity for value adaptation. To address this issue, we measured hemodynamic responses of the prefrontal cortex (PFC) in two studies on risky decision-making. In each trial, healthy human subjects chose between a risky and a safe alternative; half of the participants had to remember the risky alternatives, whereas for the other half they were presented visually. The value of safe alternatives varied across trials. PFC responses adapted to contextual risk information, with steeper coding of safe alternative value in lower-risk contexts. Importantly, this adaptation depended on working memory load, such that response functions relating PFC activity to safe values were steeper with presented versus remembered risk. An independent second study replicated the findings of the first study and showed that similar slope reductions also arose when memory maintenance demands were increased with a secondary working memory task. Formal model comparison showed that a divisive normalization model fitted effects of both risk context and working memory demands on PFC activity better than alternative models of value adaptation, and revealed that reduced suppression of background activity was the critical parameter impairing normalization with increased memory maintenance demand. Our findings suggest that mnemonic processes can constrain normalization of neural value representations.

Monocular enucleation profoundly reduces secretogranin II expression in adult mouse visual cortex.

Secretogranin II (ScgII), a member of the chromogranin family, is almost exclusively found in large dense core vesicles of a wide variety of endocrine and neuronal tissues, being stored together with many different neurotransmitters, peptide hormones and neuropeptides. In the brain ScgII is almost completely processed to secretoneurin, a peptide involved in neurite outgrowth, neuroprotection and neuronal plasticity. Furthermore, correlations with neurotransmitter release and a variety of neurological diseases were reported. In this study we examined possible changes in ScgII mRNA expression in the visual system of adult mice after removal of one eye. Mice were monocularly deprived of vision and sacrificed 1 day or 1, 3, 5 and 7 weeks after enucleation. Starting 1 day after the deprivation, a marked decrease of ScgII was visible in the contralateral visual cortex. Recovery initiated in the lateral supragranular visual cortex after 5 weeks of enucleation, but was far from complete in the 7 week animals, especially in the monocularly driven medial cortex. By comparison with the immediate early gene zif268, it was proven that ScgII cannot be categorized as an activity marker, but more likely plays a role in visual system plasticity by modulating a range of neurotransmitters and neuropeptides.